WorldWideScience

Sample records for antidepressive agents

  1. [Antidepressive agents and breast feeding].

    Science.gov (United States)

    Håberg, M; Matheson, I

    1997-11-10

    Postpartum blues occurs in 50-80% of women. A few percent of the cases are classified as serious postpartum depression, requiring antidepressant treatment. There is a growing understanding that women should continue to breast-feed in this situation. Data concerning the transfer of antidepressants into breast milk has been researched. Calculations of the infant relative dose via breast milk were done for the drugs concerned. Few antidepressants have been studied at steady state conditions in nursing mothers. Nortriptyline and amitriptyline have minimal relative doses and can be used when breast-feeding. Doxepine should be avoided, as should lithium, which has a significant transfer. Among the serotonine-reuptake inhibitors fluoxetine has been well studied in breast milk. Since fluoxetine has a long half life and a high transfer, sertraline and possibly paroxetine are better alternatives, but the latter has not yet been studied in repeated doses. Moclobemide also lacks data from multiple dose studies, but extrapolation to steady state indicates that the relative dose is small. More observational studies should be carried out in infants breast-fed by mothers using antidepressants. In the meantime, doctors prescribing antidepressant drugs to nursing mothers should see that the infants are monitored for side effects.

  2. [Antidepressive agents and suicidal tendencies].

    Science.gov (United States)

    Gründer, G; Veselinović, T; Paulzen, M

    2014-09-01

    In the last 2 years the discussions on the question whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) can lead to suicidality, aggression and violence, flared up again. The available data on the problem, which has been discussed since the introduction of this substance group in the late 1980s, is presented in this article. A systematic literature search showed that a scientific consensus exists that the benefits of antidepressant pharmacotherapy in general, and of treatment with SSRIs and selective serotonin/norepinephrine reuptake inhibitors (SSNRIs) in particular, outweigh the risks of their use. This also applies to the treatment of children, adolescents and young adults. The agitation occasionally occurring at the beginning of treatment, which can be experienced as aversive in susceptible patients, can intensify or even trigger suicidal thoughts or impulses. This has to be paid particular attention to especially at the beginning of treatment. It is recommended that the indications for antidepressant pharmacotherapy of children, adolescents and young adults are assessed by a specialist.

  3. Escitalopram versus other antidepressive agents for depression

    Science.gov (United States)

    Cipriani, Andrea; Santilli, Claudio; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; McGuire, Hugh; Churchill, Rachel; Barbui, Corrado

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs remain the mainstay of treatment in primary and secondary care settings. During the last 20 years, antidepressant prescribing has risen dramatically in western countries, mainly because of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, which have progressively become the most commonly prescribed antidepressants. Escitalopram is the pure S-enantiomer of the racemic citalopram. Objectives To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics, other SSRIs, heterocyclics and newer agents in the acute-phase treatment of major depression. Search methods Electronic databases were searched up to July 2008. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. Selection criteria All randomised controlled trials comparing escitalopram against any other antidepressant (including non-conventional agents such as hypericum) for patients with major depressive disorder (regardless of the diagnostic criteria used). Data collection and analysis Data were entered by two review authors (double data entry). Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI) using the random effects model. Main results Fourteen trials compared escitalopram with another SSRI and eight compared escitalopram with a newer antidepressive agent (venlafaxine, bupropion and duloxetine). Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (OR 0.67, 95% CI 0.50 to 0.87). Escitalopram was also more effective than citalopram in terms of remission (OR

  4. Five potential therapeutic agents as antidepressants: a brief review and future directions.

    Science.gov (United States)

    Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2015-01-01

    Despite the availability of numerous antidepressants, many patients with depression do not show adequate response. The therapeutic lag between drug administration and onset of clinical improvement observed with conventional antidepressants has led to a need for antidepressants with a novel mechanism of action. Recently, five such agents, including acetyl-L-carnitine, scopolamine, ω-3 polyunsaturated fatty acids, ketamine, and selective 5-HT7 serotonin receptor antagonists, have gained interest as potential antidepressants with enhanced symptom control, improved tolerability, and faster onset of action compared to conventional antidepressants. This review provides an update and critical examination of these five novel therapeutic agents as potential antidepressants.

  5. Duloxetine versus other anti-depressive agents for depression

    Science.gov (United States)

    Cipriani, Andrea; Koesters, Markus; Furukawa, Toshi A; Nosè, Michela; Purgato, Marianna; Omori, Ichiro M; Trespidi, Carlotta; Barbui, Corrado

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. Objectives To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. Main results A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies

  6. Agomelatine versus other antidepressive agents for major depression.

    Science.gov (United States)

    Guaiana, Giuseppe; Gupta, Sumeet; Chiodo, Debbie; Davies, Simon J C; Haederle, Katja; Koesters, Markus

    2013-12-17

    other antidepressive agent. Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. A total of 13 studies (4495 participants) were included in this review. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks. Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies. There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings, thus limiting the generalisability of the results to primary care settings. With regard to precision, the efficacy outcomes were precise, but the tolerability

  7. Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer

    Science.gov (United States)

    2015-10-01

    AD_________________ (Leave blank) Award Number: W81XWH-13-1-0211 TITLE: Development of Antidepressants as Novel Agents to Treat Small Cell Lung...DATES COVERED 1 Aug 2013 - 31 Jul 2015 4. TITLE AND SUBTITLE Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer 5a... antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells. The candidate drugs activate stress pathways

  8. Citalopram versus other anti-depressive agents for depression

    Science.gov (United States)

    Cipriani, Andrea; Purgato, Marianna; Furukawa, Toshi A; Trespidi, Carlotta; Imperadore, Giuseppe; Signoretti, Alessandra; Churchill, Rachel; Watanabe, Norio; Barbui, Corrado

    2014-01-01

    Background Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode. Systematic reviews have already highlighted some differences in efficacy between second-generation antidepressants. Citalopram, one of the first selective serotonin reuptake inhibitors (SSRI) introduced in the market, is one of these antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with tricyclics, heterocyclics, other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression. Search methods We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012. No language restriction was applied. We contacted pharmaceutical companies and experts in this field for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to citalopram versus any other antidepressants. Data collection and analysis Two reviewers independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), patient acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results Thirty-seven trials compared citalopram with other antidepressants (such as tricyclics, heterocyclics, SSRIs and other antidepressants, either conventional ones, such as mirtazapine, venlafaxine and reboxetine, or non-conventional, like hypericum). Citalopram was shown to be significantly less effective than escitalopram in achieving acute response (odds

  9. Antidepressant agents and suicide death among US Department of Veterans Affairs patients in depression treatment.

    Science.gov (United States)

    Valenstein, Marcia; Kim, Hyungjin Myra; Ganoczy, Dara; Eisenberg, Daniel; Pfeiffer, Paul N; Downing, Karen; Hoggatt, Katherine; Ilgen, Mark; Austin, Karen L; Zivin, Kara; Blow, Frederic C; McCarthy, John F

    2012-06-01

    Studies report mixed findings regarding antidepressant agents and suicide risks, and few examine suicide deaths. Studies using observational data can accrue the large sample sizes needed to examine suicide death, but selection biases must be addressed. We assessed associations between suicide death and treatment with the 7 most commonly used antidepressants in a national sample of Department of Veterans Affairs patients in depression treatment. Multiple analytic strategies were used to address potential selection biases. We identified Department of Veterans Affairs patients with depression diagnoses and new antidepressant starts between April 1, 1999, and September 30, 2004 (N = 502,179). Conventional Cox regression models, Cox models with inverse probability of treatment weighting, propensity-stratified Cox models, marginal structural models (MSM), and instrumental variable analyses were used to examine relationships between suicide and exposure to bupropion, citalopram, fluoxetine, mirtazapine, paroxetine, sertraline, and venlafaxine. Crude suicide rates varied from 88 to 247 per 100,000 person-years across antidepressant agents. In multiple Cox models and MSMs, sertraline and fluoxetine had lower risks for suicide death than paroxetine. Bupropion had lower risks than several antidepressants in Cox models but not MSMs. Instrumental variable analyses did not find significant differences across antidepressants. Most antidepressants did not differ in their risk for suicide death. However, across several analytic approaches, although not instrumental variable analyses, fluoxetine and sertraline had lower risks of suicide death than paroxetine. These findings are congruent with the Food and Drug Administration meta-analysis of randomized controlled trials reporting lower risks for "suicidality" for sertraline and a trend toward lower risks with fluoxetine than for other antidepressants. Nevertheless, divergence in findings by analytic approach suggests caution when

  10. Breast ecchymosis: Unusual complication of an antidepressant agent.

    Science.gov (United States)

    Akbulut, Sami; Yagmur, Yusuf; Gumus, Serdar; Babur, Mehmet

    2014-01-01

    Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that is safely used for treatment of psychosomatic disorders. Despite being associated with a low side effect profile, it has been reported to cause hematological side effects including vaginal bleeding, epistaxis, purpura, hematuria, intracranial bleeding, and rectal bleeding. Isolated breast ecchymosis is one of exceedingly rare SSRI-induced hematological abnormalities. In this case study, we report a case of left breast ecchymosis in a 75-year-old woman that developed in conjunction with use of the SSRI fluoxetine. The use of SSRIs has surged over the past decades due to increased diagnosis and focus on clinical management of depression and anxiety disorders, especially in developed nations. The low side effect profiles of the eight currently marketed SSRI agents has further promoted their use in the general population. While the most commonly reported side effects are mild and relatively tolerable, a risk of SSRI-related abnormal bleeding exists and may represent a life-threatening side effect. The most frequent SSRI-related bleeding manifestation is ecchymosis, but cases of isolated breast ecchymosis are exceedingly rare and to date only one report of SSRI-induced breast ecchymosis is included in the publicly available literature. Three factors may have played a role in lack of reports describing SSRI-induced breast ecchymosis in literature. First, SSRIs indeed very seldom cause breast ecchymosis; second, physicians are not aware of such a causal relationship; and third, physicians find this side effect not worth to publish. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.

    Science.gov (United States)

    Ruepert, Lisa; Quartero, A Otto; de Wit, Niek J; van der Heijden, Geert J; Rubin, Gregory; Muris, Jean Wm

    2011-08-10

    Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review. Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score. Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of  bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included. A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies

  12. The role of monoamines in the actions of established and "novel" antidepressant agents: a critical review.

    Science.gov (United States)

    Millan, Mark J

    2004-10-01

    Monoaminergic pathways are highly responsive to aversive stimuli and play a crucial role in the control of affect, cognition, endocrine secretion, chronobiotic rhythms, appetite, and motor function, all of which are profoundly disrupted in depressive states. Accordingly, a perturbation of monoaminergic transmission is implicated in the aetiology of depressive disorders, and all clinically available antidepressants increase corticolimbic availability of monoamines. However, their limited efficacy, delayed onset of action, and undesirable side effects underlie ongoing efforts to identify improved therapeutic agents. Sequencing the human genome has raised the hope not only of better symptomatic control of depression, but even of the prevention or cure of depressive states. In the pursuit of these goals, there is currently a tendency to focus on selective ligands of "novel" nonmonoaminergic targets. However, certain classes of novel agent (such as neurokinin(1) receptor antagonists) indirectly modulate the activity of monoaminergic networks. Others may act "downstream" of them, converging onto common cellular substrates controlling gene expression, synaptic plasticity, and neurogenesis. Further, by analogy to the broad-based actions of currently employed drugs, multitarget agents may be better adapted than selective agents to the management of depression-a complex disorder with hereditary, developmental, and environmental origins. It is, thus, important to continue the creative exploration of clinically validated and innovative monoaminergic strategies within a multitarget framework. In this light, drugs combining monoaminergic and nonmonoaminergic mechanisms of action may be of particular interest. The present article provides a critical overview of monoaminergic strategies for the treatment of depressive states, both established and under development, and discusses interactions of novel "nonmonoaminergic" antidepressants with monoaminergic mechanisms.

  13. Scaffold Hopping Toward Agomelatine: Novel 3, 4-Dihydroisoquinoline Compounds as Potential Antidepressant Agents

    Science.gov (United States)

    Yang, Yang; Ang, Wei; Long, Haiyue; Chang, Ying; Li, Zicheng; Zhou, Liangxue; Yang, Tao; Deng, Yong; Luo, Youfu

    2016-10-01

    A scaffold-hopping strategy toward Agomelatine based on in silico screening and knowledge analysis was employed to design novel antidepressant agents. A series of 3, 4-dihydroisoquinoline compounds were selected for chemical synthesis and biological assessment. Three compounds (6a-1, 6a-2, 6a-9) demonstrated protective effects on corticosterone-induced lesion of PC12 cells. Compound 6a-1 also displayed low inhibitory effects on the growth of HEK293 and L02 normal cells and it was further evaluated for its potential antidepressant effects in vivo. The forced swim test (FST) results revealed that compound 6a-1 remarkably reduced the immobility time of rats and the open field test (OFT) results indicated a better general locomotor activity of the rats treated with compound 6a-1 than those with Agomelatine or Fluoxetine. Mechanism studies implied that compound 6a-1 can significantly reduce PC12 cell apoptosis by up-regulation of GSH and down-regulation of ROS in corticosterone-induced lesion of PC12 cells. Meanwhile, the down-regulation of calcium ion concentration and up-regulation of BDNF level in PC12 cells may account for the neuroprotective effects. Furthermore, compound 6a-1 can increase cell survival and cell proliferation, promote cell maturation in the rat hippocampus after chronic treatment. The acute toxicity data in vivo indicated compound 6a-1 exhibited less hepatotoxicity than Agomelatine.

  14. [Antidepressants agents in breast cancer patients using tamoxifen: review of basic and clinical evidence].

    Science.gov (United States)

    Irarrázaval O, María Elisa; Gaete G, Leonardo

    2016-10-01

    Tamoxifen (Tmf), is a standard of care for women with estrogen receptor positive (ER+) breast cancer. Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Antidepressive agents (AD) are often prescribed to women with breast cancer not only for depression, but also for anxiety and hot flashes. Some AD are substrates or inhibitors of the Tmf metabolic pathway. Therefore there may be interactions when Tmf and AD are prescribed simultaneously. Oncologic protection afforded by Tmf may become less effective or null when AD are indicated, especially in poor metabolizing patients. We performed an update of the literature about the criteria for choosing AD in women receiving Tmf. Tricyclic AD, paroxetine and fluoxetine should be avoided in patients receiving Tmf, because they are strong inhibitors of CYP2D6. Bupropion, duloxetine and sertraline are only moderate inhibitors of the cytochrome and are not contraindicated. Citalopram, desvenlafaxine, escitalopram, milnacipran and venlafaxine are recommended, because they do not influence the metabolism and clinical efficacy of Tmf and have fewer drug interactions. However, other additional pharmacological and clinical issues should be considered when choosing an antidepressant in women with breast cancer.

  15. Platinum anticancer agents and antidepressants: desipramine enhances platinum-based cytotoxicity in human colon cancer cells.

    Science.gov (United States)

    Kabolizadeh, Peyman; Engelmann, Brigitte J; Pullen, Nicholas; Stewart, Jennifer K; Ryan, John J; Farrell, Nicholas P

    2012-01-01

    A unique synergistic effect on platinum drug cytotoxicity is noted in the presence of the tricyclic antidepressant desipramine. Desipramine is used for treating neuropathic pain, particularly in prostate cancer patients. The clinically used drugs cisplatin (cis-[PtCl(2)(NH(3))(2)]), oxaliplatin [1,2-diaminocyclohexaneoxalatoplatinum(II)], and the cationic trinuclear agent BBR3464 [{trans-PtCl(NH(3))(2)}(2)-μ-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2))](4+), which has undergone evaluation in phase II clinical trials for activity in lung and ovarian cancers, were evaluated. Surprisingly, desipramine greatly augments the cytotoxicity of all the platinum-based chemotherapeutics in HCT116 colorectal carcinoma cell lines. Desipramine enhanced cellular accumulation of cisplatin, but had no effect on the accumulation of oxaliplatin or BBR3464, suggesting that enhanced accumulation could not be a consistent means by which desipramine altered the platinum-drug-mediated cytotoxicity. The desipramine/cisplatin combination resulted in increased levels of p53 as well as mitochondrial damage, caspase activation, and poly(ADP ribose) polymerase cleavage, suggesting that desipramine may synergize with cisplatin more than with other platinum chemotherapeutics partly by activating distinct apoptotic pathways. The study argues that desipramine may be a means of enhancing chemoresponsiveness of platinum drugs and the results warrant further investigation. The results emphasize the importance of understanding the differential pharmacological action of adjuvants employed in combinations with cancer chemotherapeutics. © SBIC 2011

  16. [Indications for antidepressive agents in relation to diseases of the cardiovascular system].

    Science.gov (United States)

    Tikal, K; Hrabánková, M

    1993-06-01

    Antidepressants, in particular tricyclic ones (TCA), and inhibitors of monoaminooxidase (IMAO) exert a number of undesirable cardiovascular effects. TCA and IMAO frequently cause postural hypotension (PH). IMAO administration is associated with the risk of hypertensive crisis. TCA raises the heart rate and can cause abnormalities in the conduction of the cardiac excitation. TCA are contraindicated after myocardial infarction and are the cause of death after overdosage. When PH is undesirable, in hypertension and cardiac insufficiency the following safe antidepressants are recommended: nortriptyline, mianserine, trazodone and viloxazine. In abnormalities of conduction of the cardiac excitation and after myocardial infarction only mianserine, trazodione and viloxazine are recommended. With regard to cardiovascular toxicity, antidepressants from the series of selective inhibitors of serotonin reabsorption are very promising: fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. The same applies also to the reversible IMAO type A moclobemide.

  17. Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac)

    DEFF Research Database (Denmark)

    Andersen, Jacob; Stuhr-Hansen, Nicolai; Zachariassen, Linda Grønborg

    2014-01-01

    , and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent...

  18. Development of Antidepressants as Novel Agents To Treat Small Cell Lung Cancer

    Science.gov (United States)

    2014-08-01

    results led us to further investigate the effects and mech- anisms of action of the two best candidate drugs , the TCA imi- pramine and the antihistamine ...used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food...and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis

  19. Intravenous bupropion: a previously undocumented method of abuse of a commonly prescribed antidepressant agent.

    Science.gov (United States)

    Baribeau, Danielle; Araki, Keyghobad Farid

    2013-01-01

    Bupropion is an antidepressant commonly prescribed as a smoking cessation aid. It has effects on dopamine and norepinephrine, and can lower seizure threshold, particularly in overdose. Several cases of recreational use of bupropion via nasal insufflation have been reported in the literature. Here we describe a first case of intravenous bupropion dependence, with no evidence of resulting seizure activity. This addiction was sustained in part under the the premise of seeking smoking cessation aid. Pharmacokinetic interactions are explored, and the literature with respect to buproprion abuse is reviewed. We propose that bupropion may have stimulant effects amenable to abuse that vary with route of administration. Health care providers may wish to exercise additional caution when prescribing bupropion to unfamiliar patients.

  20. Antidepressants and platinum drugs.

    Science.gov (United States)

    Engelmann, Brigitte J; Ryan, John J; Farrell, Nicholas P

    2014-01-01

    Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin. The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay. The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin. The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.

  1. Potential impact of policy regulation and generic competition on sales of cholesterol lowering medication, antidepressants and acid blocking agents in Belgium.

    Science.gov (United States)

    Fraeyman, J; Van Hal, G; De Loof, H; Remmen, R; De Meyer, G R Y; Beutels, P

    2012-01-01

    Pharmaceutical expenditures are increasing as a proportion of health expenditures in most rich countries. Antidepressants, acid blocking agents and cholesterol lowering medication are major contributors to medicine sales around the globe. We aimed to document the possible impact of policy regulations and generic market penetration on the evolution of sales volume and average cost per unit (Defined Daily Doses and packages) of antidepressants, acid blocking agents and cholesterol lowering medication. We extracted data from the IMS health database regarding the public price and sales volume of the antidepressants (selective serotonin reuptake inhibitors (SSRI's), monoamine oxidase inhibitors (MAOl's) and tricyclic and remaining antidepressants (TCA's)), acid blocking agents (proton pump inhibitors (PPl's) and H2 receptor antagonists) and cholesterol lowering medication (statins and fibrates) in Belgium between 1995 and 2009. We describe these sales data in relation to various national policy measures which were systematically searched in official records. Our analysis suggests that particular policy regulations have had immediate impact on sales figures and expenditures on pharmaceuticals in Belgium: changes in reimbursement conditions, a public tender and entry of generic competitors in a reference pricing system. However, possible sustainable effects seem to be counteracted by other mechanisms such as marketing strategies, prescribing behaviour, brand loyalty and the entry of pseudogenerics. It is likely that demand-side measures have a more sustainable impact on expenditure. Compared with other European countries, generic penetration in Belgium remains low. Alternative policy regulations aimed at enlarging the generic market and influencing pharmaceutical expenditures deserve consideration. This should include policies aiming to influence physicians' prescribing and a shared responsibility of pharmacists, physicians and patients towards expenditures.

  2. Synthesis and biological evaluation of Schiff’s bases and 2-azetidinones of isonocotinyl hydrazone as potential antidepressant and nootropic agents

    Directory of Open Access Journals (Sweden)

    Asha B. Thomas

    2016-09-01

    Full Text Available The synthesis and pharmacological activity of N′-[(1Z-(substituted aromatic methylidene] pyridine-4-carbohydrazides (3a–k and N-[3-chloro-2-(substituted aromatic-4-oxoazetidin-1-yl]pyridine-4-carboxamides (5a–k are described. Synthesis of 2-azetidinones was performed by novel methods of stirring and sonication involving the cyclocondensation of the appropriate Schiff’s bases (3a–k with chloroacetyl chloride, followed by the addition of triethyl amine in the presence of molecular sieves. The compounds were investigated for their antidepressant activity, compounds N′-[(1Z-(2,5-dimethoxyphenylmethylidene]pyridine-4-carbohydrazide (3k and N-[3-chloro-2-(2,5-dimethoxyphenyl-4-oxoazetidin-1-yl]pyridine-4-carboxamide (5k with 2,5-dimethoxy substitution on the aryl ring exhibited the highest antidepressant activity. In the elevated plus maze test and passive avoidance test in mice for the evaluation of nootropic activity N′-[(1Z-(4-nitrophenylmethylidene]pyridine-4-carbohydrazide (3d and N-[3-chloro-2-(4-nitrophenyl-4-oxoazetidin-1-yl]pyridine-4-carboxamide (5d with para nitro substitution on the aryl ring exhibited the highest activity. All synthesised Schiff’s bases and azetidinone analogues exhibited antidepressant and nootropic activities in a dose dependant manner. The results confirmed the fact that the 2-azetidinone skeleton has potential as a CNS active agent and can be explored for the development of more potent and safe CNS active agents for therapeutic use.

  3. Use of Antidepressants

    Science.gov (United States)

    Kalali, Amir H.; Thase, Michael E.

    2007-01-01

    We investigated antidepressant prescriptions and reasons for use. According to our data, the top 10 molecules represent ∼95% of total antidepressant prescriptions for both primary care physicians (PCPs) and psychiatrists. The primary difference between PCPs and psychiatrists was the increased use of buproprion and tricyclics/tetracyclics by psychiatrists. The selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants such as venlafaxine (Effexor) and buproprion (Wellbutrin) are used to treat depression, anxiety, and bipolar disorders. The noted exception is duloxetine (Cymbalta), which looks like a blend between the newer agents and the tricyclics where there is use beyond the traditional central nervous system (CNS) disorders into pain and migraine. PMID:20436760

  4. Preparation of 2-[α-(2-ethoxyphenoxy)benzyl]-[5-14C]morpholine methanesulfonate ([14C]reboxetine):a new antidepressant agent

    International Nuclear Information System (INIS)

    Angiuli, P.; Fontana, E.; Vicario, G.P.

    1991-01-01

    The labelling with radiocarbon of the new antidepressant agent Reboxetine is described. The preparation has been carried out in a two step procedure using 2-chloro-N-(3-(2-ethoxyphenoxy)-2-hydroxy-3-phenyl)propyl-[1- 14 C]acetamide as starting material. The expected compound was prepared by cyclization of the above halogenoacylamido alcohol to the corresponding morpholone ring followed by reduction to the final [5- 14 C]morpholine derivative 4, 98% radiochemically pure and with specific radioactivity of 988 MBq/mmol. An overall radiochemical yield of 57.5% was achieved. (author)

  5. Antidepressant Withdrawal

    Science.gov (United States)

    ... or two, such as: Anxiety Insomnia or vivid dreams Headaches Dizziness Tiredness Irritability Flu-like symptoms, including ... your doctor may prescribe another antidepressant or another type of medication on a short-term basis to ...

  6. Tricyclic Antidepressants and Tetracyclic Antidepressants

    Science.gov (United States)

    ... 2016. Amoxapine (prescribing information). Verna, Salcette Goa, India: Watson Pharma; 2014. http://www.accessdata.fda.gov/drugsatfda_ ... mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/ART-20046983 . Mayo Clinic Footer Legal Conditions and Terms ...

  7. Antidepressants and Weight Gain

    Science.gov (United States)

    Antidepressants and weight gain: What causes it? Can antidepressants cause weight gain? Answers from Daniel K. Hall- ... is a possible side effect of nearly all antidepressants. However, each person responds to antidepressants differently. Some ...

  8. Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent.

    Science.gov (United States)

    Preskorn, Sheldon; Macaluso, Matthew; Mehra, D O Vishaal; Zammit, Gary; Moskal, Joseph R; Burch, Ronald M

    2015-03-01

    Approximately 45% of patients with major depressive disorder (MDD) do not remit when treated with biogenic amine antidepressants. Consequently, there is a significant need for antidepressant agents with different mechanisms of action. Early proof of concept (POC) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research. Studies have demonstrated that high affinity N-methyl-Daspartate (NMDA) receptor blockers (eg, ketamine) can produce rapid antidepressant effects in patients who have not responded to currently available agents, but treatment with these agents is accompanied by psychotomimetic effects that make their use problematic. This column describes a POC study involving GLYX-13, an N-methyl-D-aspartate receptor glycine site functional partial agonist. In this double-blind, randomized, placebo-controlled study, a single intravenous (IV) dose of GLYX-13 (1, 5, 10, or 30 mg/kg) or placebo was administered to 116 subjects with MDD who had not benefitted from a trial of at least one biogenic amine antidepressant during the current episode. The primary outcome measure was score on the Hamilton Depression Rating Scale-17 (Ham-D17), which was used to rate overall depressive symptoms at baseline and at 24 hours and days 3, 7, 14, and, in some arms, days 21 and 28 after administration. GLYX-13, 5 or 10 mg/kg IV, reduced depressive symptoms as assessed by the Ham-D17 at days 1 through 7. Onset of action as assessed using the Bech-6 occurred within 2 hours. GLYX-13 did not elicit psychotomimetic or other significant side effects. In this early POC study, GLYX-13 reduced depressive symptoms within 2 hours and this effect was maintained for 7 days on average in subjects with MDD who had not responded to another antidepressant agent during the current depressive episode. The findings of this study support the hypothesis that modulation of the NMDA receptor is a valid target

  9. Antidepressant-induced liver injury.

    Science.gov (United States)

    DeSanty, Kevin P; Amabile, Celene M

    2007-07-01

    To review principles of drug-induced liver injury (DILI), summarize characteristics of antidepressant-mediated liver injury, and provide recommendations for monitoring and management. A search relating to antidepressant-induced liver injury was performed using MEDLINE (1966-March 2007). Search terms included antidepressant, cholestasis, hepatotoxicity, jaundice, liver injury, toxic hepatitis, and transaminases. Reference citations not identified in the initial database search were also utilized. All English-language case reports, letters, and review articles identified from the data sources were used. Case reports and letters relating to hepatotoxicity from antidepressant overdose were excluded. Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin-norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxicity. The tricyclic antidepressants and monoamine oxidase inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease. Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.

  10. Switching antidepressants

    African Journals Online (AJOL)

    depressive disorder, with response rates of 50-60%. Switching within or between classes of antidepressants is often required in patients with an insufficient response to SSRIs.12 Because they share a similar mechanism of action, the immediate substitution of one SSRI for another is probably the easiest switching option.

  11. Tricyclic Antidepressants

    Science.gov (United States)

    Schmidt, Gary J.

    The use of tricyclic antidepressant drugs is becoming increasingly prevalent for the treatment of depressed patients. It has been suggested that, analogous to many other drug substances, the tricyclic drugs exhibit clinical effectiveness within a defined therapeutic concentration range (1-10). Very recently, both Dito (11) and Orsulak and Schildkraut (12) have summarized the usefulness of measuring serum concentrations of these drugs. These authors suggest that knowledge of the plasma concentrations of these drugs aid the physician in determining patient compliance and initiating the best possible drug treatment.

  12. Neuroimmune endocrine effects of antidepressants

    Directory of Open Access Journals (Sweden)

    Antonioli M

    2012-02-01

    Full Text Available Marco Antonioli, Joanna Rybka, LA CarvalhoPsychoimmunology Translational Laboratory, Health Science Research Centre, Roehampton University, London, UKAbstract: Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.Keywords: antidepressant agents, biological markers, human, cytokines, neuroinflammation, psychoneuroimmunology, endophenotype

  13. Antidepressants and Alcohol

    Science.gov (United States)

    ... the concern? Why is it bad to mix antidepressants and alcohol? Answers from Daniel K. Hall-Flavin, M.D. It's best to avoid combining antidepressants and alcohol. It may worsen your symptoms, and ...

  14. Safety of antidepressants

    NARCIS (Netherlands)

    Swinkels, J. A.; de Jonghe, F.

    1995-01-01

    There are a number of criteria that can be used when selecting an antidepressant. In particular safety criteria are important, and a distinction can be drawn between "safe" and "less safe" antidepressants. The relative safety of different antidepressants has been assessed by looking at answers to

  15. Antidepressants and dementia

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Søndergård, Lars; Forman, Julie Lyng

    2009-01-01

    BACKGROUND: It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. METHOD: Linkage of registers of all prescribed antidepressants and diagnoses of dementia...... the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non...... in Denmark during a period from 1995 to 2005. RESULTS: Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods...

  16. Antidepressants and dementia

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Søndergaard, Lars; Forman, Julie Lyng

    2009-01-01

    BACKGROUND: It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. METHOD: Linkage of registers of all prescribed antidepressants and diagnoses of dementia...... in Denmark during a period from 1995 to 2005. RESULTS: Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods...... the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non...

  17. Treatment of Fibromyalgia with Antidepressants

    Science.gov (United States)

    O'Malley, Patrick G; Balden, Erin; Tomkins, Glen; Santoro, James; Kroenke, Kurt; Jackson, Jeffrey L

    2000-01-01

    BACKGROUND Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options. OBJECTIVE To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression. DESIGN Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching medline, embase, and psyclit(1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction. MAIN RESULTS Sixteen randomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval [95% CI], 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressants improved sleep, fatigue, pain, and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression, only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression. CONCLUSION Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain. Whether this effect is independent of depression needs further study. PMID:11029681

  18. [Antidepressants in epilepsy].

    Science.gov (United States)

    Castaño-Monsalve, Beatriz

    2013-08-01

    Depression is a common condition in patients with epilepsy that entails a deterioration of the quality of life of this population and that, therefore, requires appropriate treatment. The potential risk of antidepressants in relation to the seizure threshold is overestimated by many professionals, and this has an influence when it comes to making the decision to treat them. It sometimes means that the patients do not receive antidepressant drugs. In this regard, the aim of this review is to present the current state of the art in terms of the safety of antidepressants in patients with epilepsy. A search of the medical literature was conducted and, following its analysis, the most significant results are presented. Current information indicates that most antidepressants are safe for epileptic patients at therapeutic doses and that the risk of seizures occurs mainly in cases of overdose. Preferred drugs for treating depression in epilepsy are serotonin reuptake inhibitors. Bupropion and tricyclic antidepressants must be avoided.

  19. [Antidepressants in bipolar disorder].

    Science.gov (United States)

    Courtet, P; Samalin, L; Olié, E

    2011-12-01

    Whereas mania defines the bipolar disorder, depression is the major challenge of treatment. In general, depressions are more frequent, longer, with a major prognostic impact in terms of disability and suicide. How should we treat a patient with bipolar depression? Antidepressants are the treatment of choice for depression, but not in the bipolar disorder. In this context, we have traditionally accepted that antidepressants are effective but they were inducing a significant risk of destabilization of the bipolar disorder, because of the transitions to mania and rapid cycling. Current data reconsider both the two aspects of this risk-benefit ratio. The effectiveness of antidepressants finally seems very limited, especially after the more recent studies with a robust methodology. Manic switches and rapid cycling may not be increased, particularly with new antidepressants and mood stabilizer combinations. The current literature reminds us that these course's modalities are inherent to the disease, with numerous risk factors, and among them, exposure to antidepressants. Who are the bipolar patients who only get the benefits of antidepressant treatment? Research will tell. They are in any case limited. How to navigate in our treatment strategies ? By choosing first drugs that demonstrated efficacy in bipolar depression. When the situation is more complex, "primum non nocere" should lead to support the prescription of the antidepressant in association with mood stabilizer. Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  20. Antidepressant Use and Incident Urinary Incontinence: A Literature Review.

    Science.gov (United States)

    Dane, Kathryn E; Gatewood, Sharon B S; Peron, Emily P

    2016-03-01

    To review available data examining antidepressant use and incident urinary incontinence (UI). PubMed was used to conduct the literature search for this review. In the primary search, the term "antidepressive agents" was searched as a medical subject heading, a pharmacological action, and a keyword phrase. This choice was made so that any relevant articles would include complete results for antidepressive agents. "Antidepressive agents" was combined with the key phrase "drug-induced urinary incontinence" to complete this primary search. Relevant articles published in English and examining human subjects were included. The study authors determined appropriateness of articles for inclusion, focusing on those examining antidepressant-associated UI. This literature review identified three cohort studies and 11 case reports examining various associations between antidepressant use and incident UI. All 11 case reports and 1 cohort study reviewed suggest an association between antidepressant use and incident UI. It remains unclear which drugs are most problematic and which patients are at greatest risk, and more data are needed to confirm an association, especially in older adults. Comprehensive medication reviews should be employed by pharmacists to identify potential medication-related causes of UI.

  1. [Clinically relevant drug interactions with new generation antidepressants and antipsychotics].

    Science.gov (United States)

    Eckert, Anne

    2009-06-01

    Because antidepressants and antipsychotics are commonly described in combination with drugs used to treat comorbid psychiatric or somatic disorders (e.g. anxiolytics, mood stabilizers, cardiovascular drugs, antimicrobial agents), they may be involved in drug interactions. Furthermore, agents such as lithium and atypical antipsychotics may be used to augment the antidepressant response in cases of refractory depression. Based on their mechanisms, drug-drug interactions can be classified either as pharmacokinetic or pharmacodynamic in nature. The well-documented risk of potentially harmful pharmacodynamic drug interactions with first-generation anti-depressants, e.g. monoamine oxidase inhibitors (MAOIs), with regard to the induction of the serotonin syndrome, has contributed to a gradual decline in their use in clinical practise. Second- and third-generation antidepressants have gradually replaced tricyclic antidepressants (TCAs) and MAOIs, mainly because of their improved tolerability and safety profile. The second- and third-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and other compounds with different mechanisms of action. These drugs and also the majority of antipsychotics are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Therefore, the use of these compounds may be associated with clinically relevant pharmacokinetic interactions with other medications. The knowledge about the CYP metabolism of drugs may be used to guide the selection of an antidepressant or an anti-psychotic with a low drug-drug interaction potential for an individual patient. The aim of the present article is to review drug-interaction potentials with specific focus on second-generation antidepressants (SSRIs), newer antidepressants (SNRIs: venlafaxine and duloxetine; bupropion, mirtazapine, trazodone), novel atypical antidepressants (agomelatine), as well as new generation

  2. Use of antidepressants: expansion beyond depression and anxiety.

    Science.gov (United States)

    Cascade, Elisa F; Kalali, Amir H; Thase, Michael E

    2007-12-01

    We investigated antidepressant prescriptions and reasons for use. According to our data, the top 10 molecules represent approximately 95% of total antidepressant prescriptions for both primary care physicians (PCPs) and psychiatrists. The primary difference between PCPs and psychiatrists was the increased use of buproprion and tricyclics/tetracyclics by psychiatrists. The selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants such as venlafaxine (Effexor) and buproprion (Wellbutrin) are used to treat depression, anxiety, and bipolar disorders. The noted exception is duloxetine (Cymbalta), which looks like a blend between the newer agents and the tricyclics where there is use beyond the traditional central nervous system (CNS) disorders into pain and migraine.

  3. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    Directory of Open Access Journals (Sweden)

    Javad Maleki

    2007-09-01

    Full Text Available  Depression is a serious disorder in today’s society, with the estimates of lifetime prevalence being as high as 21% of the general population in some developed countries. As defined by the American Psychiatric Association, depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. Such patients are often reluctant to take synthetic antidepressants in their appropriate doses due to their anticipated side effects including inability to drive a car, dry mouth, constipation, and sexual dysfunction. As a therapeutic alternative, effective herbal drugs may offer advantages in terms of safety and tolerability, possibly also improving patient compliance. The advent of the first antidepressants, Monoamine Oxidase Inhibitors (MAOIs and Tricyclic Antidepressants (TCAs, in the 1950s and 1960s represented a dramatic leap forward in the clinical management of depression. The subsequent development of the Selective Serotonin Reuptake Inhibitors (SSRIs and the Serotonin Norepinephrine Reuptake Inhibitor (SNRI venlafaxine in the past decade and a half has greatly enhanced the treatment of depression by offering patients medications that are as effective as the older agents but are generally more tolerable and safer in an overdose. The introduction of atypical antidepressants, such as bupropion, nefazadone, and mirtazapine, has added substantially to the available pharmacopoeia for depression. Nonetheless, rates of remission tend to be low and the risk of relapse and recurrence remains high. One of the concerns regarding the safety of antidepressant is its potential risk of cardiotoxicity and cardiovascular side effects. In this review, we will focus on the cardiovascular side effects of different types of antidepressants.

  4. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2007-08-01

    Full Text Available Depression is a serious disorder in today’s society, with the estimates of lifetime prevalence being as high as 21% of the general population in some developed countries. As defined by the American Psychiatric Association, depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. Such patients are often reluctant to take synthetic antidepressants in their appropriate doses due to their anticipated side effects including inability to drive a car, dry mouth, constipation, and sexual dysfunction. As a therapeutic alternative, effective herbal drugs may offer advantages in terms of safety and tolerability, possibly also improving patient compliance. The advent of the first antidepressants, Monoamine Oxidase Inhibitors (MAOIs and Tricyclic Antidepressants (TCAs, in the 1950s and 1960s represented a dramatic leap forward in the clinical management of depression. The subsequent development of the Selective Serotonin Reuptake Inhibitors (SSRIs and the Serotonin Norepinephrine Reuptake Inhibitor (SNRI venlafaxine in the past decade and a half has greatly enhanced the treatment of depression by offering patients medications that are as effective as the older agents but are generally more tolerable and safer in an overdose. The introduction of atypical antidepressants, such as bupropion, nefazadone, and mirtazapine, has added substantially to the available pharmacopoeia for depression. Nonetheless, rates of remission tend to be low and the risk of relapse and recurrence remains high. One of the concerns regarding the safety of antidepressant is its potential risk of cardiotoxicity and cardiovascular side effects. In this review, we will focus on the cardiovascular side effects of different types of antidepressants.

  5. New Generation Antidepressants in Painful Diabetic Neuropathy

    OpenAIRE

    Gutiérrez-Álvarez, Ángela-María; Moreno, Carlos B

    2011-01-01

    The incidence of diabetic neuropathy increases with the duration of diabetes and the degree of hyperglycaemia. Pain is one of the most common and incapacitating symptoms of diabetic neuropathy and its pharmacological control is complex. The effectiveness of antidepressive agents has been described in different types of neuropathic pain, but their effectiveness, when used as analgesics in painful diabetic neuropathy, still remains controversial. Objective: To review the possible role of new-ge...

  6. Pediatric Tricyclic Antidepressant Poisoning: Approach and Management

    OpenAIRE

    Roldán Ovalle, Tatiana; Hospital Universitario de San Ignacio; López Millán, Angelo; Hospital Universitario de San Ignacio

    2016-01-01

    Antidepressants are agents that cause significant morbidity and mortality with important toxicity particularly on cardiovascular and neurological systems, which is mainly based on their pharmacology and is that determines specific treatment. Unfortunately, children are vulnerable population because the increase in psychiatric disorders which are treated with these drugs. The purpose of this article is to review the pharmacokinetics, clinical presentation and treatment of acute poisoning with ...

  7. Sertraline: a new antidepressant.

    Science.gov (United States)

    Auster, R

    1993-08-01

    Sertraline is a serotonin reuptake inhibitor that has been approved for use in the treatment of depression. Its side-effect profile is similar to that of fluoxetine, a drug of the same class. The side effects of these drugs most often affect the gastrointestinal tract. Serotonin reuptake inhibitors are nonsedating and free of cardiac effects; they do not cause hypotension, urinary retention or blurred vision. Sertraline, like fluoxetine, appears to be safer than tricyclic antidepressants in overdose. However, no clinical studies comparing sertraline and fluoxetine have been published. The wholesale cost of a month's supply of sertraline is about $50, compared with about $5 for a generic tricyclic antidepressant. Despite their cost, serotonin uptake inhibitors may be the initial drugs of choice in depressed elderly patients, because these patients are at increased risk for suicide and have a low tolerance for the side effects of tricyclic antidepressants.

  8. [Multimodal serotonergic antidepressants].

    Science.gov (United States)

    Danilov, D S

    Based on the original literature, the author for the first time describes a history of selective serotonergic antidepressants simultaneously inhibiting the serotonin reuptake and directly interacting with serotonin receptors. A history of creation and introduction of their main representatives is presented. A history of investigation of their neurochemical activity is analyzed in details. The history of the evolution of their classifications is systemized. The data presented suggest the rationale for unifying all selective serotonergic antidepressants, simultaneously inhibiting the serotonin reuptake and directly interacting with serotonin receptors (trazodone, etoperidone, nefazodone, vilazodone, vortioxetine), in one group of 'multimodal serotonergic antidepressants'. The expediency to include this group in the modern neurochemical classification of nootropic drugs is substantiated.

  9. Ketamine: A New Antidepressant?

    Directory of Open Access Journals (Sweden)

    Feride Karacaer

    2015-03-01

    Full Text Available Standart antidepressants are needed for the many individuals with major depressive disorder. However they do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent studies show that subanesthetic dose of ketamine is efficacy and safety for the treatment of depression. Antidepressant effects of ketamine have been found to be short-lived and its psychotomimetic properties may limit the use of ketamine to depressive patients. Future research studies should focus on identifying predictors of response (pharmalogical and clinical , investigating application of different doses and routes of administration and maintaining antidepressant effect. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 30-40

  10. Adherence to antidepressants

    Directory of Open Access Journals (Sweden)

    Abimbola Farinde

    2013-01-01

    Full Text Available While major depression is considered a frequent mental illness there are ongoing reports of high non-adherence to antidepressant medications which places suffers at high risk for relapse, recurrence, or greater impairment,. The World Health Organization (WHO defines adherence as the extent to which a person′s behavior (e.g. taking medications can align with the agreed recommendations of a health care provider. Unfortunately while patient may recognize the importance of adherence to antidepressant medications the majority of patients do not adhere to their prescribed antidepressants. Some of the factors that may contribute to or lead to non-adherence include knowingly or unknowingly missing doses, taking extra doses, delaying administration times, or taking drug holidays. Pharmacists have the unique ability to deter non-adherence through the performance of continuous assessment and monitoring of adherence in this population given these accessibility. Additionally, pharmacists are able to develop therapeutic alliances with patients that can help to increase the likelihood of achieving positive patient outcomes. Antidepressant non-adherence can be viewed as a significant public health concern so it is important for patients to be educated about the importance of adherence, and health care professionals should be aware of factors or patient characteristics that can serve as barriers to non-adherence.

  11. Antidepressant medications and osteoporosis

    DEFF Research Database (Denmark)

    Rizzoli, R; Cooper, C; Reginster, J-Y

    2012-01-01

    Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major...

  12. Adverse reactions to antidepressants

    DEFF Research Database (Denmark)

    Uher, Rudolf; Farmer, Anne; Henigsberg, Neven

    2009-01-01

    (74%), constipation (33%) and weight gain (15%) were associated with nortriptyline treatment. Diarrhoea (9%), insomnia (36%) and yawning (16%) were more common during treatment with escitalopram. Problems with urination and drowsiness predicted discontinuation of nortriptyline. Diarrhoea and decreased......Background: Adverse drug reactions are important determinants of non-adherence to antidepressant treatment, but their assessment is complicated by overlap with depressive symptoms and lack of reliable self-report measures. Aims: To evaluate a simple self-report measure and describe adverse...... comparing escitalopram and nortriptyline. Results: There was good agreement between self-report and psychiatrists' ratings. Most complaints listed as adverse reactions in people with depression were more common when they were medication-free rather than during their treatment with antidepressants. Dry mouth...

  13. Diving and antidepressants.

    Science.gov (United States)

    Querido, Abraham L

    2017-12-01

    Psychoactive drugs pose a risk to both the diver and his or her buddy. Little is known about the safety of diving with antidepressants. Amongst the potential interactions with the diving environment are: somnolence; convulsions; a bleeding tendency (potentially worsening decompression illness, DCI), alterations to glucose metabolism and psychiatric side effects. Fluoxetine may potentially reduce the inflammatory process associated with DCI. This article presents guidelines for recreational diving in combination with antidepressants. These guidelines were endorsed at a meeting of the Dutch Association for Diving Medicine in 2015 and are solely based on 'expert' opinion. Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in printed and other forms.

  14. Milnacipran: a unique antidepressant?

    Directory of Open Access Journals (Sweden)

    Siegfried Kasper

    2010-08-01

    Full Text Available Siegfried Kasper, Gerald PailDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, AustriaAbstract: Tricyclic antidepressants (TCAs are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in ­overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs are ­better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and ­norepinephrine reuptake inhibitors (SNRIs. Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine, and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1. Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug–drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.Keywords: milnacipran, SNRI, antidepressant efficacy, tolerability

  15. Growth and change in the prescribing of anti-depressants in New Zealand: 1993-1997.

    Science.gov (United States)

    Roberts, E; Norris, P

    2001-02-09

    To examine changes in the prescribing of anti-depressants in New Zealand from 1993-1997, in terms of expenditure, the number of dispensings and days of therapy supplied. Data on subsidised dispensings of anti-depressant drugs during 1993 to 1997 were obtained from PHARMAC and analysed using SAS. The overall size of the anti-depressant market increased considerably over the study period. Government expenditure rose 2.25 times, and 1.65 times as many days of anti-depressant medication were supplied in 1997 as in 1993. Most of this was due to the growth in prescribing of newer anti-depressants, but the use of older drugs remained constant. In common with other countries, the use of newer agents is contributing to increased overall use of anti-depressant medication and government expenditure in New Zealand. Use of older drugs has not diminished substantially.

  16. Mechanisms of antidepressant resistance

    Directory of Open Access Journals (Sweden)

    Wissam eEl Hage

    2013-11-01

    Full Text Available Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder. However, there is a wide range of variability in response to antidepressants that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to antidepressant therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes.

  17. The role of dopamine and norepinephrine in depression and antidepressant treatment.

    Science.gov (United States)

    Nutt, David J

    2006-01-01

    Most antidepressants in use today are descendants of the monoamine oxidase inhibitor iproniazid and the tricyclic agent imipramine. These agents were both originally developed for other indications but then were serendipitously determined to have antidepressant effects. Elucidation of the mechanisms of action of these first antidepressants, along with those of reserpine and amphetamine, led to the monoamine theories of depression. Through the past several decades, approaches undertaken to clarify the roles of the neurotransmitters norepinephrine, dopamine, and serotonin in depression have included animal studies, human biological and postmortem studies, inferences drawn from antidepressant drug actions, and challenge or depletion studies; most recently, brain imaging studies have proved to be especially informative. This research has identified novel potential targets, with the goal of developing new antidepressant drugs with better efficacy and faster onset of action than current "gold-standard" treatments.

  18. Behavioral evidence of antidepressant-like activity of Raphanus ...

    African Journals Online (AJOL)

    Background: Currently-available antidepressant agents produce various adverse effects, and are expensive. At present, various plants are being evaluated for their possible role against numerous diseases, and no doubt, the role of traditional and complementary medicines in the development of effective therapy is ...

  19. Tricyclic antidepressant radioreceptor assay

    International Nuclear Information System (INIS)

    Innis, R.B.; Tune, L.; Rock, R.; Depaulo, R.; U'Prichard, D.C.; Snyder, S.M.

    1979-01-01

    A receptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [ 3 H]-3-guinuclidnyl benzilate ( 3 H-QNB) for binding to muscarinic cholinergic receptors in rat brain membranes. The assay is sensitive, in that it can detect, for example, 2ng/ml nortriptyline in plasma. Seven plasma samples from depressed patients treated with nortriptyline were assayed with the radioreceptor and gas liquid chromatographic methods, and the results from these two methods were almost identical. This assay should be used cautiously, if at all, in patients treated with other drugs that have potent anticholinergic effects. (Auth.)

  20. A prospective naturalistic study of antidepressant-induced jitteriness/anxiety syndrome

    Directory of Open Access Journals (Sweden)

    Harada T

    2014-11-01

    .Keywords: side effects, antidepressants, selective serotonin-reuptake inhibitors, tricyclic antidepressive agents, suicide

  1. Effects of Antidepressants on Sleep.

    Science.gov (United States)

    Wichniak, Adam; Wierzbicka, Aleksandra; Walęcka, Małgorzata; Jernajczyk, Wojciech

    2017-08-09

    The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment. Complaints of disrupted sleep are very common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder. Moreover, midnocturnal insomnia is the most frequent residual symptom of depression. Thus, all antidepressants should normalize sleep. However, at least in short-term treatment, many antidepressants with so-called activating effects (e.g. fluoxetine, venlafaxine) may disrupt sleep, while others with sedative properties (e.g., doxepin, mirtazapine, trazodone) rapidly improve sleep, but may cause problems in long-term treatment due to oversedation.For sleep-promoting action, the best effects can frequently be achieved with a very low dose, administered early enough before bedtime and importantly, always as a part of more complex interventions based on the cognitive-behavioral protocol to treat insomnia (CBT-I). For successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Each physician should also be aware that some antidepressants may worsen or induce primary sleep disorders like restless legs syndrome, sleep bruxism, REM sleep behavior disorder, nightmares, and sleep apnea, which may result from an antidepressant-induced weight gain.

  2. [Antidepressants in the elderly].

    Science.gov (United States)

    Cortajarena García, M C; Ron Martin, S; Miranda Vicario, E; Ruiz de Vergara Eguino, A; Azpiazu Gomez, P J; Lopez Aldana, J

    2016-10-01

    Depression in the elderly is a changing, difficult and common disorder. At this age, there are more relapses and more long-life treatment is required. The pharmacology approach is a challenge because of concurrent factors that make their treatment more difficult. It is very important to have a basic antidepressant scheme, in order to help treat this disorder with efficiency and success from Primary Care. There are no drugs without side effects, and their characteristics have to be known in order to make the right selection depending on effectiveness, safety and tolerance. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Differing antidepressant maintenance methodologies.

    Science.gov (United States)

    Safer, Daniel J

    2017-10-01

    The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

  4. Antidepressant-selective gynecomastia.

    Science.gov (United States)

    Kaufman, Kenneth R; Podolsky, Dina; Greenman, Danielle; Madraswala, Rehman

    2013-01-01

    To describe what we believe is the first reported case of synergistic gynecomastia during treatment of depressive and anxiety disorders when sertraline was added to a stable medication regimen including duloxetine, rosuvastatin, and amlodipine. A 67-year-old male with major depression, dysthymia, obsessive-compulsive disorder, social anxiety, hypertension, diabetes, and hyperlipidemia presented with new-onset gynecomastia and breast tenderness. Mammography revealed bilateral gynecomastia (fibroglandular tissue posterior to the nipples bilaterally) without suspicious mass, calcification, or other abnormalities. These new symptoms developed after sertraline was added to his stable medication regimen (duloxetine, alprazolam, rosuvastatin, metoprolol, amlodipine, hydrochlorothiazide/triamterene, metformin, and sitagliptin). These symptoms were dose-dependent, with gynecomastia and breast tenderness more severe as sertraline was titrated from 25 mg/day to 50 mg/day and then to 75 mg/day. When sertraline was discontinued, gynecomastia and breast tenderness rapidly resolved. Mammoplasia and gynecomastia are associated with altered dopamine neurotransmission and/or perturbations in sexual hormones. These adverse effects may be medication induced. Selective serotonin reuptake inhibitors (sertraline), serotonin-norepinephrine reuptake inhibitors (duloxetine), rosuvastatin, and amlodipine have been reported to cause these adverse effects. This case was unique, since the patient had been on both sertraline and duloxetine previously as independent psychotropics without the development of gynecomastia. In the context of an additive drug adverse effect, the probability of sertraline as the precipitant drug was determined by both the Naranjo probability scale and the Horn drug interaction probability scale as probable. Gynecomastia is associated with antidepressants and other medications but is rarely addressed. Gynecomastia may be antidepressant selective or may be the result of

  5. Antidepressants: Can They Lose Effectiveness?

    Science.gov (United States)

    ... be having the same effect. Can antidepressants lose effectiveness? Answers from Daniel K. Hall-Flavin, M.D. ... Policy Notice of Privacy Practices Notice of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  6. Biosynthesis of catecholamines, uptake of 3H-noradrenaline, and reactivity of cardiovascular system of the rat after chronic and acute treatment with a new antidepressant agent, IPF C-45

    International Nuclear Information System (INIS)

    Filczewski, M.; Szymanska-Kosmala, M.; Oledzka, K.

    1977-01-01

    The effect of acute and chronic treatment of rats with IPF C-45 on the following biochemical and pharmacological parameters was tested: catecholamine concentration in brain, heart and adrenals, 3 H-noradrenaline uptake by cardiac muscle, the action on catecholamine synthesis following treatment with alpha-methyl-p-tyrosine, reactivity of cardiovascular system to catecholamines and isproterenol-induced tachycardia. Given chronically, IPF C-45 does not affect noradrenaline uptake by the cardia muscle. Both chronic and acute administration of the drug decelerates catecholamine biosynthesis by inhibition of tyrosine hydroxylase activity. It seems that the action of IPF C-45, a benzonaphthyridone derivative, affects catecholamine metabolism in a manner distinctly different from that of tricyclic antidepressant drugs. (author)

  7. [Antidepressants and pregnancy: risks and benefits for the mother and child].

    Science.gov (United States)

    Bérard, Anick; Ramos, Elodie

    2007-11-01

    Depression, anxiety disorders, anorexia nervosa and bulimia, all indications for antidepressant use, are common disorders in women of childbearing age. Nevertheless, antidepressant use during the gestational period remains a controversial topic. Given that 50 % of pregnancies are unplanned, the safety of antidepressants during the first trimester of pregnancy, a critical period for foetal development, has become a major public health concern. Until now, most studies suggest that physicians may often under-prescribe or discontinue antidepressants at the time of conception and during pregnancy. This may be a consequence of the concern over the safety of these agents in pregnant women and the risks they may pose to the foetus. In fact, recent studies and warnings from Health Canada and the US Food and Drug Administration have reinforced this uncertainty regarding the adverse effects of antidepressant use on the foetus. On the other hand, discontinuation of antidepressant use during pregnancy was also recently associated with maternal relapse of depression and withdrawal symptoms, which is not optimal for the mother and her foetus. Consequently, women who wish to become pregnant and who suffer from psychiatric disorders are faced with the difficult task of deciding whether to continue or discontinue their antidepressant during pregnancy. At this time, it appears important to take into account all evidence-based data to evaluate the risks/benefits of using antidepressants during the gestational period in order to help mothers make the best choice for themselves, and their infants.

  8. Antidepressants and sleep: a qualitative review of the literature.

    Science.gov (United States)

    Wilson, Sue; Argyropoulos, Spilios

    2005-01-01

    Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs

  9. Antidepressants versus placebo for panic disorder in adults.

    Science.gov (United States)

    Bighelli, Irene; Castellazzi, Mariasole; Cipriani, Andrea; Girlanda, Francesca; Guaiana, Giuseppe; Koesters, Markus; Turrini, Giulia; Furukawa, Toshi A; Barbui, Corrado

    2018-04-05

    Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes, and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. It is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, the National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology consider antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several classes of antidepressants have been studied and compared, but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition. To assess the effects of antidepressants for panic disorder in adults, specifically:1. to determine the efficacy of antidepressants in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison to placebo;2. to review the acceptability of antidepressants in panic disorder, with or without agoraphobia, in comparison with placebo; and3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo. We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews. All double-blind, randomised, controlled trials (RCTs

  10. Survey of treatment practices for sexual dysfunction(s) associated with anti-depressants.

    Science.gov (United States)

    Balon, Richard; Segraves, R Taylor

    2008-01-01

    There are many management strategies and antidotes available for sexual dysfunction associated with antidepressants available. However, only a few of these strategies and antidotes were tested in rigorous trials and most of them probably will not be rigorously tested. Surveying the prescribing practices of experts in this area provides another opportunity to evaluate these strategies and antidotes. The authors surveyed 29 (of 50) "expert" psychiatrists in the area of sexual dysfunction associated with antidepressants. Switching to another antidepressant, decreasing the dose of an antidepressant, and adding oral agents such as bupropion, phosphodiesterase-5 inhibitors, and some dopaminergic agents (dextroamphetamine, methylphenidate) and a testosterone patch in some dysfunctions (libido, orgasm) are management strategies most frequently used by the experts. The experts also consider these strategies as the most effective ones. These findings are compared with other studies and discussed with regard to the evidence from clinical trials.

  11. Are Antidepressants Effective in the Treatment of Postpartum Depression? A Systematic Review

    OpenAIRE

    Sharma, Verinder; Sommerdyk, Christina

    2013-01-01

    Objective: In spite of the paucity of randomized controlled trials of antidepressants in postpartum depression, these drugs are the most commonly used agents in the pharmacologic treatment of postpartum depression. This article reviews the literature on the efficacy of antidepressants in randomized controlled trials of postpartum depression. Data Sources: Four electronic databases, MEDLINE/PubMed (1966–2013), PsycINFO (1806–2013), EMBASE (1980–2013), and the Cochrane Database of Systematic Re...

  12. Antidepressant Prescribing Patterns in Korea: Results from the Clinical Research Center for Depression Study

    OpenAIRE

    Bae, Kyung-Yeol; Kim, Sung-Wan; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Jung, Sung-Won; Lee, Min-Soo; Yim, Hyeon-Woo; Jun, Tae-Youn

    2011-01-01

    Objective This study aimed to investigate antidepressant prescribing patterns, including initial choice, switching and combining, and concomitant use of non-antidepressant agents, for depressive disorders in naturalistic clinical care settings in Korea. Methods Patients with depressive disorder were recruited from both outpatient and inpatient settings in 18 hospitals from all over Korea. Treatment was performed in naturalistic patterns based on each clinician's decision. Data were collected ...

  13. The Timing of Antidepressant Effects: A Comparison of Diverse Pharmacological and Somatic Treatments

    Directory of Open Access Journals (Sweden)

    Carlos A. Zarate Jr.

    2010-01-01

    Full Text Available Currently available antidepressants used to treat major depressive disorder (MDD unfortunately often take weeks to months to achieve their full effects, commonly resulting in considerable morbidity and increased risk for suicidal behavior. Our lack of understanding of the precise cellular underpinnings of this illness and of the mechanism of action of existing effective pharmacological treatments is a large part of the reason that therapies with a more rapid onset of antidepressant action (ROAA have not been developed. Other issues that need to be addressed include heterogeneous clinical concepts and statistical models to measure rapid antidepressant effects. This review describes the timing of onset of antidepressant effects for various therapies used to treat MDD. While several agents produce earlier improvement of depressive symptoms (defined as occurring within one week, the response rate associated with such agents can be quite variable. These agents include both currently available antidepressants as well as other pharmacological and non-pharmacological interventions. Considerably fewer treatments are associated with ROAA, defined as occurring within several hours or one day. Treatment strategies for MDD whose sustained antidepressant effects manifest within hours or even a few days would have an enormous impact on public health.

  14. Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants?

    Science.gov (United States)

    Park, Susie H; Wackernah, Robin C; Stimmel, Glen L

    2014-02-01

    There is a warning associated with all serotonergic antidepressants and its concomitant use with tramadol due to the concern for a drug-drug interaction resulting in serotonin syndrome (SS). The prescribing of antidepressants with tramadol may be unnecessarily restricted due to fear of causing this syndrome. There are 3 objectives of this review. To (1) review case reports of SS associated with the combination of tramadol and antidepressant drugs in recommended doses, (2) describe the mechanisms of the drug interaction, and (3) identify the potential risk factors for SS. Case reports of SS associated with tramadol and antidepressants were identified via Cochrane Library, PubMed, and Ovid (through October 2012) using search terms SS, tramadol, antidepressants, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, venlafaxine, desvenlafaxine, duloxetine, mirtazapine, milnacipran, trazodone, vilazodone, and bupropion. Cases involving monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants were excluded. Nine articles were identified describing 10 cases of suspected SS associated with therapeutic doses of tramadol combined with an antidepressant. Mechanisms of the drug-drug interactions involve pharmacodynamic, pharmacokinetic, and possible pharmacogenetic factors. Review of the available case reports of tramadol combined with antidepressant drugs in therapeutic doses indicates caution in regard to the potential for SS but does not constitute a contraindication to their use. Tramadol is only contraindicated in combination with MAOIs but not other antidepressants in common use today. These case reports do suggest several factors associated with a greater risk of SS, including increased age, higher dosages, and use of concomitant potent cytochrome P450 2D6 inhibitors. Tramadol can be safely combined with antidepressants; however, monitoring and counseling patients are prudent when starting a new serotonergic agent or when doses are

  15. Migraine Medications and Antidepressants: A Risky Mix?

    Science.gov (United States)

    ... health risks associated with taking migraine medications and antidepressants at the same time? Answers from Jerry W. ... that combining migraine medications called triptans with certain antidepressants — including selective serotonin reuptake inhibitors (SSRIs) and serotonin ...

  16. Placebo-Activated Neural Systems are Linked to Antidepressant Responses

    Science.gov (United States)

    Peciña, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Langenecker, Scott A.; Mickey, Brian J.; Zubieta, Jon-Kar

    2016-01-01

    Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. Objective Here we examined neurochemical mechanisms underlying the formation of placebo effects in patients with Major Depressive Disorder (MDD). Participants Thirty-five medication-free MDD patients. Design and Intervention We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either “active” or “inactive” fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the μ-opioid receptor (MOR)-selective radiotracer [11C]carfentanil after each 1-week “inactive” and “active” oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Setting A University Health System. Main Outcomes and Measures Changes in depressive symptoms in response to “active” placebo and antidepressant. Baseline and activation measures of MOR binding. Results Higher baseline MOR binding in the nucleus accumbens (NAc) was associated with better response to antidepressant treatment (r=0.48; p=0.02). Reductions in depressive symptoms after 1-week of “active” placebo treatment, compared to the “inactive”, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the

  17. Antidepressant-Resistant Depression and Antidepressant-Associated Suicidal Behaviour: The Role of Underlying Bipolarity

    Directory of Open Access Journals (Sweden)

    Zoltan Rihmer

    2011-01-01

    Full Text Available The complex relationship between the use of antidepressants and suicidal behaviour is one of the hottest topics of our contemporary psychiatry. Based on the literature, this paper summarizes the author's view on antidepressant-resistant depression and antidepressant-associated suicidal behaviour. Antidepressant-resistance, antidepressant-induced worsening of depression, antidepressant-associated (hypomanic switches, mixed depressive episode, and antidepressant-associated suicidality among depressed patients are relatively most frequent in bipolar/bipolar spectrum depression and in children and adolescents. As early age at onset of major depressive episode and mixed depression are powerful clinical markers of bipolarity and the manic component of bipolar disorder (and possible its biological background shows a declining tendency with age antidepressant-resistance/worsening, antidepressant-induced (hypomanic switches and “suicide-inducing” potential of antidepressants seem to be related to the underlying bipolarity.

  18. Effect of antidepressants on neuroendocrine axis in humans.

    Science.gov (United States)

    Meltzer, H Y; Fang, V S; Tricou, B J; Robertson, A

    1982-01-01

    Unlike neuroleptic drugs, the effect of antidepressant drugs on the neuroendocrine axis in man is highly variable and may or may not be intimately related to their antidepressant action. However, the limited neuroendocrine data available does shed some light on the mechanism of action of these agents and raises some important questions, particularly about the regulation of PRL secretion and the interaction between various neurotransmitter systems. At one end of the spectrum, the ability of nomifensine and buproprion to lower serum PRL levels, presumably due to their ability to block the reuptake of DA by tuberoinfundibular DA neurons, suggests that it may be necessary to reconsider the conclusion that these neurons lack a DA reuptake mechanism or that these two agents are antidepressant by virtue of their ability to block DA uptake. Similarly, the inability of amphetamine or methylphenidate to decrease serum PRL levels in man suggests important differences between the tuberoinfundibular DA neurons in man and the rat. These findings also call into question the ability of these agents to block DA uptake or increase DA release in the tuberoinfundibular DA neurons. The finding that fluoxetine raises serum PRL levels, even in one subject, whereas zimelidine has not yet been shown to do so, and that fluoxetine does not potentiate the ability of 5-HTP to stimulate PRL secretion, has raised important questions about the role of 5-HT in PRL and GH regulation in man and the relationship between 5-HT and DA neurons in man. The occasional increase in serum PRL levels found in patients treated with lithium or the MAO inhibitor phenelzine are suggestive of important interindividual differences which may be revealed by neuroendocrine studies, differences which could be valuable in understanding the mechanism of action of these agents - e.g., does lithium decrease DA receptor sensitivity? - and fundamental aspects of neuroendocrine regulation - e.g., do the MAO inhibitors

  19. Antidepressants and the risk of hyponatremia

    DEFF Research Database (Denmark)

    Leth-Møller, Katja Biering; Hansen, Annette Højmann; Torstensson, Maia

    2016-01-01

    OBJECTIVE: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. DESIGN: Retrospective register-based cohort study using nationwide registers from 1998 to 2012. SETTING: The North Denmark Region. PARTICIPANTS: In total....../L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. RESULTS: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs.......14). CONCLUSIONS: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine....

  20. [Interactions between metoprolol and antidepressants].

    Science.gov (United States)

    Molden, Espen; Spigset, Olav

    2011-09-20

    Metoprolol, the most commonly used beta-receptor antagonist in Norway, is eliminated mainly via the enzyme cytochrome P450 (CYP) 2D6. This enzyme is inhibited to a varying extent by antidepressants. The aim of this article is to provide an overview of the interactions between metoprolol and antidepressants with an emphasis on CYP2D6 inhibition. Relevant literature was identified by a PubMed search using the word "metoprolol" combined with generic names of antidepressant drugs. The potent CYP2D6 inhibitor paroxetine has been shown to increase the biologically available dose of metoprolol about 4- to 6-fold. The same degree of increase is expected for the two other potent CYP2D6 inhibitors in the class, fluoxetine and bupropion. Severe bradycardia and atroventricular block has been reported in patients who have taken metoprolol in combination with these three drugs. Escitalopram, citalopram and duloxetine are less potent CYP2D6 inhibitors, and have been shown to cause 2- to 3-fold increases in biologically available dose of metoprolol. Other antidepressants, such as sertraline, venlafaxine, mianserin and mirtazapine, inhibit CYP2D6 to little or no extent, and are not expected to cause clinically relevant interactions with metoprolol. Metoprolol should not be used concomitantly with paroxetine, fluoxetine or bupropion due to extensive interactions and the risk of serious adverse effects. Dose reductions of metoprolol should be considered for combined treatment with citalopram, escitalopram or duloxetine, while concurrent use with sertraline, venlafaxine, mianserin and mirtazapine should be safe.

  1. Procarbazine and antidepressants: a retrospective review of the risk of serotonin toxicity.

    Science.gov (United States)

    Kraft, Shawna L; Baker, Nicole M; Carpenter, Julia; Bostwick, Jolene R

    2014-01-01

    Procarbazine is an anticancer agent that also inhibits monoamine oxidase, an enzyme responsible for the metabolism of various catecholamines, including serotonin. A retrospective chart review of lymphoma patients who were treated with both procarbazine and an antidepressant, as well as procarbazine alone, was performed to determine if signs and symptoms of serotonin toxicity were present. A total of 65 patients received procarbazine between 2004 and 2010 and were eligible to be included in the study. Twenty-six of these patients received an antidepressant in combination with procarbazine, with selective serotonin reuptake inhibitors being the most common type of antidepressant. No patients in the study were diagnosed with serotonin toxicity, nor did any meet Hunter's diagnostic criteria for serotonin toxicity. Diarrhea, tremor, and shivering were the symptoms from Sternbach's criteria that were further analyzed, with diarrhea occurring 8.54% of the time, tremor occurring 5.53% of the time, and shivering occurring 2.51% of the time in patients who received an antidepressant with their procarbazine. Despite these symptoms, the diagnosis of serotonin toxicity according to Sternbach's criteria was determined to be unlikely. In this small sample of patients treated with procarbazine plus an antidepressant (most typically SSRIs), there were no reports of serotonin toxicity, nor did any patients demonstrate symptoms consistent with serotonin toxicity. The authors urge clinicians to ensure depression is adequately managed in cancer patients who are undergoing procarbazine therapy, starting with typical first-line antidepressant agents. Copyright © 2013 John Wiley & Sons, Ltd.

  2. A brief history of antidepressant drug development: from tricyclics to beyond ketamine.

    Science.gov (United States)

    Pereira, Vitor Silva; Hiroaki-Sato, Vinícius Antonio

    2018-02-01

    Although monoaminergic-targeted drugs have prompted great advances in the development of treatments for depression, the need for new options persists, since these drugs still have a delayed clinical effect and most patients do not respond properly to them. Recently, the observation of the antidepressant effects of ketamine brought on a new wave of studies regarding the comprehension of the neurobiology of depression and the development of new and more effective antidepressant drugs. Thus, in this paper, we present a historical review of the development of monoaminergic antidepressant drugs and the role of ketamine as the introductory agent of a new era in the research of the neurobiology of depression. Firstly, we review how the pharmacological treatment for major depression started, and we point out the main drugs discovered, the researchers involved, and how the studies developed have contributed to the understanding of the neurobiology of depression. Secondly, the major problems regarding the clinical efficacy and acceptance of these drugs are discussed, and the introduction of the glutamatergic system as a target for antidepressant drugs is presented. Finally, we review how ketamine revealed itself as an exciting option towards obtaining pharmacological agents to treat depression, through the understanding of biological markers. Discussion Ketamine contributed to confirm that different targets of the glutamatergic system and neurotrophic pathways are strictly related to the neurobiology of depression. There are several antidepressant drugs based on ketamine's mechanism of action already in the pipeline, and glutamatergic-targeted antidepressants may be on the market in the near future.

  3. Influence of antidepressants on hemostasis

    Science.gov (United States)

    Halperin, Demian; Reber, Guido

    2007-01-01

    Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition - fluoxetine, paroxetine, and sertraline - are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge

  4. Antidepressant activity of curcumin: involvement of serotonin and dopamine system.

    Science.gov (United States)

    Kulkarni, Shrinivas K; Bhutani, Mohit Kumar; Bishnoi, Mahendra

    2008-12-01

    Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

  5. Serotonergic anti-depressants and ethanol withdrawal syndrome: a review.

    Science.gov (United States)

    Uzbay, I Tayfun

    2008-01-01

    To review laboratory findings on the effects of anti-depressant agents that interact with the serotonergic system on signs of ethanol withdrawal syndrome in rats. Adult Wistar rats received a modified liquid diet to produce ethanol dependence. Signs of ethanol withdrawal, locomotor hyperactivity, stereotyped behaviour, tremor, wet dog shakes, agitation, and audiogenic seizures, were evaluated for the first 6 h of ethanol withdrawal. The effects of the anti-depressants fluoxetine, venlafaxine, escitalopram, tianeptine, and extract of Hypericum perforatum (St. John's wort) (HPE) were examined. Some beneficial effects of fluoxetine, tianeptine, HPE, escitalopram and venlafaxine on ethanol withdrawal signs were observed, ranked as follows: fluoxetine = tianeptine > HPE > escitalopram > venlafaxine. Tianeptine and fluoxetine seem to be potent pharmacologically active agents on ethanol withdrawal syndrome in rats. Thus, these anti-depressants may be useful in treatment of ethanol withdrawal syndrome in patients with alcoholism. In addition to serotonergic effects, interactions with nitrergic, glutamatergic, and adenosinergic systems may also provide a significant contribution to the beneficial effects of these drugs on ethanol withdrawal syndrome.

  6. Antidepressant treatment for postnatal depression.

    Science.gov (United States)

    Molyneaux, Emma; Howard, Louise M; McGeown, Helen R; Karia, Amar M; Trevillion, Kylee

    2014-09-11

    Postnatal depression is a common disorder that can have adverse short- and long-term effects on maternal morbidity, the new infant and the family as a whole. Treatment is often largely by social support and psychological interventions. It is not known whether antidepressants are an effective and safe choice for treatment of this disorder. This review was undertaken to evaluate the effectiveness of different antidepressants and to compare their effectiveness with other forms of treatment, placebo or treatment as usual. It is an update of a review first published in 2001. To assess the effectiveness of antidepressant drugs in comparison with any other treatment (psychological, psychosocial or pharmacological), placebo or treatment as usual for postnatal depression. We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialized Register (CCDANCTR) to 11 July 2014. This register contains reports of relevant randomised controlled trials (RCTs) from the following bibliographic databases: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE, (1974 to date) and PsycINFO (1967 to date). We also searched international trial registries and contacted pharmaceutical companies and experts in the field. We included RCTs of women with depression with onset up to six months postpartum that compared antidepressant treatment (alone or in combination with another treatment) with any other treatment, placebo or treatment as usual. Two review authors independently extracted data from the trial reports. We requested missing information from investigators wherever possible. We sought data to allow an intention-to-treat analysis. Random effects meta-analyses were conducted to pool data where sufficient comparable studies were identified. We included six trials with 596 participants in this review. All studies had a randomised controlled parallel group design, with two conducted in the UK, three in the US and one in Israel. Meta-analyses were performed to pool

  7. Antidepressants for the treatment of depression in people with cancer.

    Science.gov (United States)

    Ostuzzi, Giovanni; Matcham, Faith; Dauchy, Sarah; Barbui, Corrado; Hotopf, Matthew

    2015-06-01

    .83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the quality of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity. Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.

  8. Ionization pattern obtained in electrospray ionization or atmospheric pressure chemical ionization interfaces for authorized antidepressants in Romania

    Science.gov (United States)

    Grecu, Iulia; Ionicǎ, Mihai; Vlǎdescu, Marian; Truţǎ, Elena; Sultan, Carmen; Viscol, Oana; Horhotǎ, Luminiţa; Radu, Simona

    2016-12-01

    Antidepressants were found in 1950. In the 1990s there was a new generation of antidepressants. They act on the level of certain neurotransmitters extrasinpatic by its growth. After their mode of action antidepressants may be: SSRIs (Selective Serotonin Reuptake Inhibitors); (Serotonin-Norepinephrine Reuptake Inhibitors); SARIs (Serotonin Antagonist Reuptake Inhibitors); NRIs (Norepinephrine Reuptake Inhibitors); NDRIs (Norepinephrine-Dopamine Reuptake Inhibitors) NDRAs (Norepinephrine-Dopamine Releasing Agents); TCAs (Tricyclic Antidepressants); TeCAs (Tetracyclic Antidepressants); MAOIs (Monoamine Oxidase Inhibitors); agonist receptor 5-HT1A (5- hydroxytryptamine); antagonist receptor 5-HT2; SSREs (Selective Serotonin Reuptake Enhancers) and Sigma agonist receptor. To determine the presence of antidepressants in biological products, it has been used a system HPLC-MS (High Performance Liquid Chromatography - Mass Spectrometry) Varian 12001. The system is equipped with APCI (Atmospheric Pressure Chemical Ionization) or ESI (ElectroSpray Ionization) interface. To find antidepressants in unknown samples is necessary to recognize them after mass spectrum. Because the mass spectrum it is dependent on obtaining private parameters work of HPLC-MS system, and control interfaces, the mass spectra library was filled with the mass spectra of all approved antidepressants in Romania. The paper shows the mass spectra obtained in the HPLCMS system.

  9. Combination antidepressants - use by GPs and psychiatrists.

    Science.gov (United States)

    Horgan, David; Dodd, Seetal

    2011-06-01

    Current treatment of depression fails to achieve remission in 50% of patients. Combinations of two antidepressants are used by some Australian psychiatrists. This article investigates the pros and cons of combination antidepressant therapy and provides suggestions for when to consider their use, which combinations to choose, and how to introduce combination antidepressant therapies. Combining two antidepressants is a controversial strategy, with supporters and critics arguing its efficacy and safety from opposing perspectives. The use of combination antidepressant therapies may facilitate remission from depression. However, there is limited evidence supporting these treatments, and safety concerns are often cited. There is some support for combination therapies in selected cases from international bodies. After considering risks and benefits on a case-by-case basis, careful use of selected combination antidepressant therapy may be one of a range of effective treatments for some individuals suffering from depression.

  10. Antidepressants and benzodiazepines for panic disorder in adults.

    Science.gov (United States)

    Bighelli, Irene; Trespidi, Carlotta; Castellazzi, Mariasole; Cipriani, Andrea; Furukawa, Toshi A; Girlanda, Francesca; Guaiana, Giuseppe; Koesters, Markus; Barbui, Corrado

    2016-09-12

    A panic attack is a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. Panic disorder is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, antidepressants and benzodiazepines are the mainstay of treatment for panic disorder. Different classes of antidepressants have been compared; and the British Association for Psychopharmacology, and National Institute for Health and Care Excellence (NICE) consider antidepressants (mainly selective serotonin reuptake inhibitors (SSRIs)) as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In addition to antidepressants, benzodiazepines are widely prescribed for the treatment of panic disorder. To assess the evidence for the effects of antidepressants and benzodiazepines for panic disorder in adults. The Specialised Register of the Cochrane Common Mental Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference lists of relevant papers and previous systematic reviews were handsearched. We contacted experts in this field for supplemental data. All double-blind randomised controlled trials allocating adult patients with panic disorder to antidepressants or benzodiazepines versus any other active treatment with antidepressants or benzodiazepines. Two review authors independently checked eligibility and extracted data using a standard form. Data were

  11. Prenatal Antidepressants and Autism Spectrum Disorder

    Science.gov (United States)

    2014-09-01

    1 AWARD NUMBER: W81XWH-13-1-0306 TITLE: Prenatal Antidepressants and Autism Spectrum Disorder PRINCIPAL INVESTIGATOR...TYPE Annual 3. DATES COVERED 1Sept 2013-31Aug2014 4. TITLE AND SUBTITLE Prenatal Antidepressants and Autism Spectrum Disorder 5a... antidepressants (ADs) during pregnancy. We are testing this hypothesis in rodents. The study is a 2-year long experiment to be decoded and

  12. Antidepressants and risk of dementia in migraine patients: A population-based case-control study.

    Science.gov (United States)

    Lee, Cynthia Wei-Sheng; Lin, Cheng-Li; Lin, Pan-Yen; Thielke, Stephen; Su, Kuan-Pin; Kao, Chia-Hung

    2017-07-03

    To ascertain the relationship between receipt of antidepressant agents and the risk of subsequent dementia in migraine patients. A population-based case-control analysis, using the Taiwan National Health Insurance Research Database. We identified 1774 patients with dementia and 1774 matched nondementia controls from migraine patients enrolled in the Taiwan National Health Insurance program between 2005 and 2011. The proportional distributions of exposure to three classes of antidepressant were compared between dementia and nondementia groups. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of dementia based on antidepressant exposure. The proportions of subjects taking tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and new-generation antidepressants (NGAs) in dementia versus nondementia groups are 52.3 vs 51.2%, 25.5 vs 30.7%, and 18.8 vs 6.26%, respectively. The adjusted ORs of dementia were 1.02 (95% CI=0.89, 1.17; P=0.56) for TCAs, 0.58 (95% CI=0.50, 0.69; Pdementia in migraine patients. TCAs showed no association with dementia risk, and NGAs showed increased risk. Given the possibility of confounding by indication, additional prospective trials and basic research are needed before drawing conclusions about the population-level risks for dementia onset conferred by antidepressant medications. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Antidepressants and gastrointestinal symptoms in the general Dutch adult population

    NARCIS (Netherlands)

    Schurink, B.; Tielemans, M.M.; Aaldering, B.R.; Eikendal, T.; Jaspers Focks, J.; Laheij, R.J.F.; Jansen, J.B.M.J.; Rossum, L.G.M. van; Oijen, M.G.H. van

    2014-01-01

    BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general

  14. Antidepressant-like effect of modafinil in mice: Evidence for the involvement of the dopaminergic neurotransmission.

    Science.gov (United States)

    Mahmoudi, Javad; Farhoudi, Mehdi; Talebi, Mahnaz; Sabermarouf, Babak; Sadigh-Eteghad, Saeed

    2015-06-01

    Modafinil is a wake-promoting agent that provides wide ranges of neurological effects. There is evidence that it can produce antidepressant effects. This study investigated the antidepressant effect of modafinil in the tail suspension (TST) in mice. Different doses of modafinil was intraperitoneally (ip) administrated and then animals were subjected to TST and/or open field test (OFT). Moreover, the implication of the dopaminergic neurotransmission in modafinil's antidepressant effect was studied. For this purpose, animals were pretreated with haloperidol (non-selective dopamine receptor antagonist), or SCH23390 and sulpiride (the dopamine D1 and D2 receptor antagonist, respectively), then were assessed by TST. The possible effect of sub-effective dose of modafinil in combination with sub-therapeutic doses of standard antidepressants was also evaluated in separate groups. Modafinil (75 mg/kg, ip) produced antidepressant effect in TST, as compared to a control group, without any alterations in ambulation in OFT. Pretreatment of mice with haloperidol (0.2mg/kg, ip) and sulpride (50mg/kg, ip) blocked the anti-immobility effect of modafinil (75 mg/kg, ip). We also found that the administration of SCH23390 (0.05 mg/kg, sc) couldn't antagonize the antidepressant effects of modafinil. In addition, a sub-effective dose of modafinil (50mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1mg/kg, ip), fluoxetine (1mg/kg, ip) and imipramine (0.1mg/kg, ip) and reduced immobility time in TST. Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D2 receptors) system. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study.

    Science.gov (United States)

    Olfson, Mark; Marcus, Steven C; Shaffer, David

    2006-08-01

    The Food and Drug Administration has issued a boxed warning concerning increased suicidal ideation and behavior associated with antidepressant drug treatment in children and adolescents. It is unknown whether antidepressant agents increase the risk of suicide death in children or adults. To estimate the relative risk of suicide attempt and suicide death in severely depressed children and adults treated with antidepressant drugs vs those not treated with antidepressant drugs. Matched case-control study. Outpatient treatment settings in the United States. Medicaid beneficiaries from all 50 states who received inpatient treatment for depression, excluding patients treated for pregnancy, bipolar disorder, schizophrenia or other psychoses, mental retardation, dementia, or delirium. Controls were matched to cases for age, sex, race or ethnicity, state of residence, substance use disorder, recent suicide attempt, number of days since hospital discharge, and recent treatment with antipsychotic, anxiolytic/hypnotic, mood stabilizer, and stimulant medications. Suicide attempts and suicide deaths. In adults (aged 19-64 years), antidepressant drug treatment was not significantly associated with suicide attempts (odds ratio [OR], 1.10; 95% confidence interval [CI], 0.86-1.39 [521 cases and 2394 controls]) or suicide deaths (OR, 0.90; 95% CI, 0.52-1.55 [86 cases and 396 controls]). However, in children and adolescents (aged 6-18 years), antidepressant drug treatment was significantly associated with suicide attempts (OR, 1.52; 95% CI, 1.12-2.07 [263 cases and 1241 controls]) and suicide deaths (OR, 15.62; 95% CI, 1.65-infinity [8 cases and 39 controls]). In these high-risk patients, antidepressant drug treatment does not seem to be related to suicide attempts and death in adults but might be related in children and adolescents. These findings support careful clinical monitoring during antidepressant drug treatment of severely depressed young people.

  16. An electronic health record driven algorithm to identify incident antidepressant medication users.

    Science.gov (United States)

    Bobo, William V; Pathak, Jyotishman; Kremers, Hilal Maradit; Yawn, Barbara P; Brue, Scott M; Stoppel, Cynthia J; Croarkin, Paul E; St Sauver, Jennifer; Frye, Mark A; Rocca, Walter A

    2014-01-01

    We validated an algorithm designed to identify new or prevalent users of antidepressant medications via population-based drug prescription records. We obtained population-based drug prescription records for the entire Olmsted County, Minnesota, population from 2011 to 2012 (N=149,629) using the existing electronic medical records linkage infrastructure of the Rochester Epidemiology Project (REP). We selected electronically a random sample of 200 new antidepressant users stratified by age and sex. The algorithm required the exclusion of antidepressant use in the 6 months preceding the date of the first qualifying antidepressant prescription (index date). Medical records were manually reviewed and adjudicated to calculate the positive predictive value (PPV). We also manually reviewed the records of a random sample of 200 antihistamine users who did not meet the case definition of new antidepressant user to estimate the negative predictive value (NPV). 161 of the 198 subjects electronically identified as new antidepressant users were confirmed by manual record review (PPV 81.3%). Restricting the definition of new users to subjects who were prescribed typical starting doses of each agent for treating major depression in non-geriatric adults resulted in an increase in the PPV (90.9%). Extending the time windows with no antidepressant use preceding the index date resulted in only modest increases in PPV. The manual abstraction of medical records of 200 antihistamine users yielded an NPV of 98.5%. Our study confirms that REP prescription records can be used to identify prevalent and incident users of antidepressants in the Olmsted County, Minnesota, population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. Neuroplasticity and the next wave of antidepressant strategies.

    Directory of Open Access Journals (Sweden)

    Shawn eHayley

    2013-11-01

    Full Text Available Depression is a common chronic psychiatric disorder that is also often co-morbid with numerous neurological and immune diseases. Accumulating evidence indicates that disturbances of neuroplasticity occur with depression, including reductions of hippocampal neurogenesis and cortical synaptogenesis. Improper trophic support stemming from stressor-induced reductions of growth factors, most notably brain derived neurotrophic factor (BDNF, likely drives such aberrant neuroplasticity. We posit that psychological and immune stressors can interact upon a vulnerable genetic background to promote depression by disturbing BDNF and neuroplastic processes. Furthermore, the chronic and commonly relapsing nature of depression is suggested to stem from faulty wiring of emotional circuits driven by neuroplastic aberrations. The present review considers depression in such terms and attempts to integrate the available evidence indicating that the efficacy of current and next wave antidepressant treatments, whether used alone or in combination, is at least partially tied to their ability to modulate neuroplasticity. We particularly focus on the NMDA antagonist, ketamine, which already has well documented rapid antidepressant effects, and the trophic cytokine, erythropoietin, which we propose as a potential adjunctive antidepressant agent.

  18. Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

    Directory of Open Access Journals (Sweden)

    Peizhong Mao

    2011-01-01

    Full Text Available Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

  19. [Prevalence of Avoidable Potential Interactions Between Antidepressants and Other Drugs in Colombian Patients].

    Science.gov (United States)

    Machado-Alba, Jorge E; Morales-Plaza, Cristhian David

    2013-06-01

    To determine the possible drugs interactions with antidepressive agents in data bases of patients in the Health Insurance System of Colombia. From data bases of about 4 million users in Colombia, a systematic review of drugs dispensation statistics was made to identify drug interactions between antidepressive agents, cholinergic antagonists and tramadol in 2010. We identified 114,465 monthly users of antidepressive agents. Of these, 5776 (5.0%) received two, and 178 (0.2%) received three antidepressive agents simultaneously. The most frequent combination was fluoxetine+trazodone (n=3235; 56.9% of cases). About 1127 (1.0%) patients were prescribed a cholinergic antagonist simultaneously; 2523 (2.1%) users were dispensed tramadol at the same time, while raising the risk of serotonin syndrome. Drug interactions represent a potential risk that is often underestimated by physicians. Pharmacovigilance is a useful tool to optimize resources and prevent negative outcomes associated with medication. It is recommended that systematic search is made to enhance surveillance programs for the rational use of medicines in this country. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  20. Antidepressant prescribing in five European countries

    DEFF Research Database (Denmark)

    Abbing-Karahagopian, V; Huerta, C; Souverein, P C

    2014-01-01

    , sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10...

  1. Antidepressant induced sexual dysfunction, part 1: epidemiology ...

    African Journals Online (AJOL)

    ... their compliance with medication and ultimately the prognosis of their illness. This review will be presented in two parts. The first part focuses on the prevalence of antidepressant induced sexual dysfunction and its clinical presentation both generally and in the case of individual classes of antidepressants. The second part ...

  2. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

    2005-01-01

    Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit...... presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated...... in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral...

  3. Should patients with schizophrenia receive antidepressants?

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Joffe, Grigori

    Antipsychotics play a key role in the pharmacological treatment of schizophrenia, and monotherapy is effective for most patients. Achieving an optimal treatment response is, however, often difficult. Combining an antidepressant drug to the antipsychotic regimen could potentially improve treatment outcomes, although the evidence supporting the use of such combinations is limited and contradictory. Positive evidence has mostly been obtained from the efficacy of antidepressants acting on monoamine receptors on the negative symptoms of schizophrenia. These receptor-active drugs may also improve cognition in schizophrenic patients. In the light of current knowledge, antidepressants do not appear to potentiate the psychotic symptoms of schizophrenic patients. However, there is no robust evidence of the efficacy of antidepressants in the treatment of schizophrenia-related depression, and thus monotherapy with an antipsychotic drug is recommended for treating it. If using antidepressants in addition to antipsychotics is deemed necessary, the risk of pharmacodynamic and pharmacokinetic interactions should be kept in mind.

  4. Depression, antidepressants, and sexual function.

    Science.gov (United States)

    Victor, B S

    1995-08-01

    Recent studies have suggested that serotonin reuptake inhibitors (SSRI's), prescribed for the relief of depression, can cause sexual dysfunction in up to fifty percent of those taking them. The SSRI's--including fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)--affect mood stabilization by promoting the transmission of the neurotransmitter serotonin, although enhancing serotonergic function can decrease libido or lead to erectile difficulties. As an alternative to lowering antidepressant dosages and risking losing therapeutic gains, administering serotonin-blockers, such as cyproheptadine (Periactin) and yohimbine (Yocon), has been shown to restore sexual function. However, the serotonin antagonist, cyproheptadine, causes sedation and can reverse the antidepressant or anti-obsessive effect of the SSRI. Yohimbine enhances transmission of the neurotransmitter epinephrine, increasing the flow of blood to erectile tissue and stimulating sexual desire by activating the cerebral cortex. Its drawbacks are increased levels of panic attacks and higher required dosages. Other potential biochemical stratagems are: amantadine (Symmetrel), bromcriptine (Parlodel), and buspirone (Buspar), which enhance dopamine and serotonin transmission; and bethanecol (Urechline), which enhances choline transmission. One study indicates improved sexual response when the nonserotonergic, mildly dopamine-enhancing buproprion (Welbutrin) is substituted for fluoxetine.

  5. Clinically significant drug interactions with newer antidepressants.

    Science.gov (United States)

    Spina, Edoardo; Trifirò, Gianluca; Caraci, Filippo

    2012-01-01

    After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at

  6. Relabeling the Medications We Call Antidepressants

    Directory of Open Access Journals (Sweden)

    David Antonuccio

    2012-01-01

    Full Text Available This paper raises the question about whether the data on the medications we call antidepressants justify the label of antidepressant. The authors argue that a true antidepressant should be clearly superior to placebo, should offer a risk/benefit balance that exceeds that of alternative treatments, should not increase suicidality, should not increase anxiety and agitation, should not interfere with sexual functioning, and should not increase depression chronicity. Unfortunately, these medications appear to fall short on all of these dimensions. Many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size. To call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective. Consumers deserve a label that more accurately reflects the data on the largest effects and helps them understand the range of effects from these medications. In other words, it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common. It can be argued that a misleading label may interfere with our commitment to informed consent. Therefore, it may be time to stop calling these medications antidepressants.

  7. Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice.

    Science.gov (United States)

    Li, Xia; Need, Anne B; Baez, Melvyn; Witkin, Jeffrey M

    2006-10-01

    Antidepressant-like effects of metabotropic glutamate (mGlu)5 receptor antagonists have been reported previously. We now provide definitive identification of mGlu5 receptors as a target for these effects through the combined use of selective antagonists and mice with targeted deletion of the mGlu5 protein. In these experiments, the mGlu5 receptor antagonists 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and the more selective and metabolically stable analog 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) decreased immobility in the mouse forced swim test, a test predictive of antidepressant efficacy in humans. mGlu5 receptor knockout mice had a phenotype in the forced swim test that was congruent with the effects of receptor blockade; mGlu5 receptor knockout mice were significantly less immobile than their wild-type counterparts. Consistent with mGlu5 receptor mediation of the antidepressant-like effects of MPEP, the effects of MPEP were not observed in mGlu5 receptor knockout mice, whereas comparable effects of the tricyclic antidepressant imiprimine remained active in the mutant mice. MPEP and imiprimine resulted in a synergistic antidepressant-like effect in the forced swim test. The drug interaction was not likely because of increased levels of drugs in the brain, suggesting a pharmacodynamic interaction of mGlu5 and monoaminergic systems in this effect. Thus, the present findings substantiate the hypothesis that mGlu5 receptor antagonism is associated with antidepressant-like effects. This mechanism may not only provide a novel approach to the therapeutic management of depressive disorders but also may be useful in the augmentation of effects of traditional antidepressant agents.

  8. Antidepressant medication use and breast cancer risk.

    Science.gov (United States)

    Wernli, Karen J; Hampton, John M; Trentham-Dietz, Amy; Newcomb, Polly A

    2009-04-01

    Most epidemiologic studies have detected no association between prior use of antidepressant medications and breast cancer risk. Despite the uniform conclusion, there is a continuous rise in the proportion of women using antidepressants, lending support to further monitoring of disease effects. We conducted a population-based case-control study among 2908 incident breast cancer cases diagnosed from 2003 to 2006, and 2927 control women from Wisconsin. Associations between antidepressant use and breast cancer risk were evaluated using multivariable logistic regression. The association between use of antidepressant medications and breast cancer risk was null (OR = 0.89, 95%CI 0.78-1.01). When stratified by type of antidepressant, use of selective-serotonin reuptake inhibitors (SSRIs) resulted in a similar risk overall (OR = 0.85, 95%CI 0.72-1.00) and among former and currents users. There were no associations between other types of antidepressant classes and breast cancer risk. In assessing risks among the five most commonly used antidepressants, we detected no association with fluoxetine, sertraline, venlafaxine, or buproprion hydrochloride. There was a reduction in breast cancer risk of 36% (OR = 0.64, 95%CI 0.45-0.92) among users of paroxetine hydrochloride. When stratified by body mass index, there was a reduction in risk associated with antidepressant users who were not overweight (OR = 0.73, 95% CI 0.60-0.90), but this association was null in overweight women (p-interaction = 0.04). Surveillance of health risks associated with antidepressant medications continues to be of public health importance, though these medications are not likely to be associated with breast cancer risk.

  9. Treatment with antiparkinson and antidepressant drugs

    DEFF Research Database (Denmark)

    Brandt-Christensen, Mette; Kvist, Kajsa; Nilsson, Flemming Mørkeberg

    2007-01-01

    Depressive symptoms and major depression are frequent in patients with Parkinson's disease (PD). However, a systematic knowledge about the treatment with antidepressant drugs among PD patients is missing. We estimated the frequency of antidepressant drug treatment in a national sample of persons......,029,737 persons were included. Persons who got APDs had significantly increased rate ratios (RR) of subsequent antidepressant drug treatment compared with an unexposed control group (RR: 2.10 (95% CI: 2.04-2.16)) and with persons who got anti-diabetic drugs [RR: 1.58 (95% CI: 1.51-1.65)]. Persons treated...... and depression....

  10. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

    Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally......, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well...

  11. Placebo and antidepressant treatment for major depression

    DEFF Research Database (Denmark)

    Hougaard, Esben

    2010-01-01

    Antidepressant medication is generally considered the primary treatment for major depressive disorders (MDD), but antidepressant treatment has recently approached a crisis with shrinking specific effects and growing placebo responses in current trials. The aim of the paper is to review the placebo...... problem within antidepressant treatment for MDD, and to draw lines to similar problems within the field of psychotherapy. Although clinicians might profit from the large placebo response in their treatment of MDD, the small differences between active treatment and placebo groups found in controlled...

  12. Anti-depressants and suicide.

    Science.gov (United States)

    Ludwig, Jens; Marcotte, Dave E; Norberg, Karen

    2009-05-01

    Suicide takes the lives of around a million people each year, most of whom suffer from depression. In recent years there has been growing controversy about whether one of the best-selling anti-depressants - selective serotonin reuptake inhibitors (SSRIs) - increases or decreases the risk of completed suicide. Randomized clinical trials are not informative in this application because of small samples and other problems. We present what we believe are the most scientifically credible estimates to date on how SSRI sales affect suicide mortality using data from 26 countries for up to 25 years. We exploit just the variation in SSRI sales that can be explained by institutional differences in how drugs are regulated, priced, and distributed, as reflected by the sales growth of new drugs more generally. We find an increase in SSRI sales of 1 pill per capita (12% of 2000 sales levels) reduces suicide by 5%.

  13. Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: a Review.

    Science.gov (United States)

    de Oliveira, Marcos Roberto; Chenet, Aline Lukasievicz; Duarte, Adriane Ribeiro; Scaini, Giselli; Quevedo, João

    2017-07-10

    Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss. Treatment with anti-depressants provides a complete remission of symptoms in approximately 50% of patients with major depression. However, these drugs may cause side effects, as sedation and weight gain. In this context, there is increasing interest in studies focusing on the anti-depressant effects of natural compounds found in the diet. Resveratrol is a polyphenolic phytoalexin (3,4',5-trihydroxystilbene; C 14 H 12 O 3 ; MW 228.247 g/mol) and has been found in peanuts, berries, grapes, and wine and induces anti-oxidant, anti-inflammatory, and anti-apoptotic effects in several mammalian cell types. Resveratrol also elicits anti-depressant effects, as observed in experimental models using animals. Therefore, resveratrol may be viewed as a potential anti-depressant agent, as well as may serve as a model of molecule to be modified aiming to ameliorate depressive symptoms in humans. In the present review, we describe and discuss the anti-depressant effects of resveratrol focusing on the mechanism of action of this phytoalexin in different experimental models.

  14. Antidepressants and Gastric Cancer: A Nationwide Population-Based Nested Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Yi-Hsuan Hsieh

    Full Text Available To our knowledge, no epidemiological study has reported on whether an association between antidepressant exposure and gastric cancer exists. Herein, we aim to investigate the possible association between antidepressant exposure and gastric cancer incidence.Using a nested case-control design, we identified 26289 cases with gastric cancer and 127984 controls from Taiwan's National Health Insurance Research Database (NHIRD. The data were analyzed using a conditional logistic regression model adjusting for possible confounding variables.We found antidepressant use did not increase the risk of gastric cancer. The lack of an association between antidepressant prescription and elevated gastric cancer incidence was apparent for across selective serotonin-reuptake inhibitors (SSRIs, tricyclic agents (TCAs, serotonin-norepinephrine reuptake inhibitors (SNRIs, reversible inhibitors of monoamine oxidase A (RIMA, trazodone, mirtazapine and bupropion. There were slightly decreased gastric cancer risks of SSRIs use (≧28 DDD group, adjusted OR = 0.87; 95% CI = 0.78-0.96. Sensitive analysis showed SSRIs, TCAs, and SNRIs did not increase gastric cancer risks significantly even in the group with peptic ulcer history.An association between antidepressant exposure and gastric cancer was not apparent in this analysis.

  15. Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr

    2010-01-01

    Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The curren...... study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients.......Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The current...

  16. 'In my life antidepressants have been…': a qualitative analysis of users' diverse experiences with antidepressants.

    Science.gov (United States)

    Gibson, Kerry; Cartwright, Claire; Read, John

    2016-05-11

    While mental health professionals have focused on concerns about whether antidepressants work on a neurochemical level it is important to understand the meaning this medication holds in the lives of people who use it. This study explores diversity in the experience of antidepressant users. One thousand seven hundred forty-seven New Zealand antidepressant users responded to an open-ended question about their experience of antidepressants. This was analysed using content and thematic analysis. There was considerable diversity in participants' responses including positive (54 %), negative (16 %) and mixed (28 %) experiences with antidepressants. Those with positive experiences saw antidepressants as a necessary treatment for a 'disease', a life saver, a way of meeting social obligations, dealing with difficult circumstances or a stepping stone to further help. Negative themes described antidepressants as being ineffective, having unbearable side effects, undermining emotional authenticity, masking real problems and reducing the experience of control. Mixed experience themes showed how participants weighed up the unpleasant side effects against the benefits, felt calmer but less like themselves, struggled to find the one or dosage and felt stuck with continuing on antidepressants when they wished to stop. Mental health professions need to recognize that antidepressants are not a 'one size fits all' solution.

  17. New generation of antidepressants in pregnant women

    Directory of Open Access Journals (Sweden)

    Ladan Kashani

    2007-03-01

    Full Text Available Although pregnancy was once thought to protect against psychiatric disorders, gravid and non gravid women have similar risks for major depression, at 10% to 15%. Both depression and antidepressant treatment during pregnancy have been associated with risks. Few medications have been proved unequivocally safe during pregnancy. Although certain antidepressants have not been linked with an increased risk of birth defects or impaired development including bupropion, citalopram, escitalopram and venlafaxine, the latest studies aren't necessarily reassuring. As researchers continue to learn more about antidepressants, the risks and benefits of taking the drugs during pregnancy must be weighed carefully on a case-by-case basis. This review discusses about the use of new generation of antidepressants in pregnancy

  18. Capgras syndrome responding to the antidepressant mirtazapine.

    Science.gov (United States)

    Khouzam, Hani Raoul

    2002-01-01

    A new onset of Capgras syndrome, delusional misidentification, developed in an elderly gentleman. Treatment with the antidepressant mirtazapine led to the remission. Suggestions are made for both dynamic and medical bases for Capgras syndrome and possible antipsychotic effects of mirtazapine.

  19. The effects of antidepressants on gastric ulcer

    Directory of Open Access Journals (Sweden)

    Mehmet Latif Güneş

    2013-12-01

    Full Text Available In their daily practice, psychiatrists often experience gastriccomplaints in patients beside psychiatric disorders.Peptic ulcer is one of the diseases, which accompanyto psychiatric disorders including mainly depression. Itis shown that antidepressants can inflame the bleedingsincluding gastrointestinal (GI bleedings, while they havepositive effect on ulcer healing. In this review, studies,which conducted about the positive or negative effects ofantidepressant drugs on ulcer treatment were examined.Accordingly; it was found that opipramol, amitriptyline,imipramine that of tricyclic antidepressants was found tobe helpful in healing of the ulcer. It was stated that SelectiveSerotonin Reuptake Inhibitors generally inflamedulcers, exceptionally fluvoxamine and fluoxetine reducedulcer; moclobemide that of monoamine-oxidase inhibitorand tianeptine and mirtazapine that of atypical antidepressantshad positive effect in ulcer healing. To be carefulin choosing the appropriate antidepressant in psychiatricpatients with gastric ulcer is important in the prognosisof both ulcer and depression.Key words: peptic ulcer; depression; antidepressant drugs

  20. Antidepressants: MedlinePlus Health Topic

    Science.gov (United States)

    ... Medical Education and Research) Genetics Genetics Home Reference: depression (National Library of Medicine) Statistics and Research Antidepressant Use in Persons Aged 12 and Over: United States, 2005-2008 (National Center for Health Statistics) Clinical ...

  1. Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study.

    Science.gov (United States)

    Bergman, Joseph; Miodownik, Chanoch; Bersudsky, Yuly; Sokolik, Shmuel; Lerner, Paul P; Kreinin, Anatoly; Polakiewicz, Jacob; Lerner, Vladimir

    2013-01-01

    Depression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression. Forty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression-Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale. Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study. Although there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.

  2. Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain

    Directory of Open Access Journals (Sweden)

    Undieh Ashiwel S

    2008-01-01

    Full Text Available Abstract Background Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [3H]cytidine-labeled CDP-diacylglycerol and [3H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors. Results Multiple compounds from each antidepressant category significantly stimulated [3H]CDP-diacylglycerol accumulation in cerebrocortical, hippocampal, and striatal tissues, and also enhanced the resynthesis of inositol phospholipids. Conversely, various antipsychotics, anxiolytics, and non-antidepressant psychotropic agents failed to significantly induce CDP-diacylglycerol or phosphoinositide synthesis. Drug-induced CDP-diacylglycerol accumulation was independent of lithium and only partially dependent on phosphoinositide hydrolysis, thus indicating that antidepressants

  3. Pharmacogenetics of antidepressant response: An update

    Directory of Open Access Journals (Sweden)

    Drago Antonio

    2009-04-01

    Full Text Available Abstract The past few decades have witnessed much progress in the field of pharmacogenetics. The identification of the genetic background that regulates the antidepressant response has benefited from these advances. This review focuses on the pharmacogenetics of the antidepressant response through the analysis and discussion of the most compelling evidence in this line of research. Online databases (Medline and PsycINFO have been searched and the most replicated association findings relating to the genetics of the antidepressant response have been reported and discussed. Some replicated findings in the literature have suggested the serotonin transporter promoter (5-HTTLPR, serotonin receptor 1A (HTR1A, serotonin receptor 2A (HTR2A, brain derived neurotrophic factor (BDNF, corticotropin releasing hormone receptor 1 (CRHR1 and FK506 binding protein 5 (FKBP5 as putative regulators of the antidepressant response. A high rate of failure of replication has also been reported. Pharmacogenetics will hopefully provide the basis for personalised antidepressant treatment that is able to maximise the probability of a good response and to minimise side effects; however, this goal is not achievable at the moment. The extent of the validity of the replicated findings and the reasons for the poor results obtained from studies of the pharmacogenetics of the antidepressant response are discussed.

  4. Fall and Fracture Risk in Nursing Home Residents With Moderate-to-Severe Behavioral Symptoms of Alzheimer's Disease and Related Dementias Initiating Antidepressants or Antipsychotics.

    Science.gov (United States)

    Wei, Yu-Jung; Simoni-Wastila, Linda; Lucas, Judith A; Brandt, Nicole

    2017-05-01

    Both antidepressants and antipsychotics are used in older adults with behavioral symptoms of Alzheimer's disease and related dementias. Despite the prevalent use of these agents, little is known about their comparative risks for falls and fractures. Using 2007-2009 Medicare claims data linked to Minimum Data Set 2.0, we identified new users of antidepressants and antipsychotics among nursing home residents with Alzheimer's disease and related dementias who had moderate-to-severe behavioral symptoms. Separate discrete-time survival models were used to estimate risks of falls, fractures, and a composite of both among antidepressant group versus antipsychotic group. Compared to antipsychotic users, antidepressant users experienced significantly higher risk for fractures (adjusted hazard ratio = 1.35, 95% confidence interval = 1.10-1.66). The overall risk of falls or fractures remained significant in the antidepressant versus antipsychotic group (adjusted hazard ratio = 1.16, 95% confidence interval = 1.02-1.32). Antidepressants are associated with higher fall and fracture risk compared to antipsychotics in the management of older adults with Alzheimer's disease and related dementias who experience moderate-to-severe behavioral symptoms. Clinicians need to assess the ongoing risks/benefits of antidepressants for these symptoms especially in light of the increasingly prevalent use of these agents. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. The effect of antidepressants on fertility.

    Science.gov (United States)

    Casilla-Lennon, Marianne M; Meltzer-Brody, Samantha; Steiner, Anne Z

    2016-09-01

    Information on the effects of different pharmaceuticals on fertility is sparse. Human and animal models indicate that antidepressant use could have a negative effect on fertility through alteration of levels of the neurosteroid, allopregnanolone. The objective of this study is to assess the effects of antidepressants on the natural fertility in women. A secondary analysis of data from Time to Conceive, a prospective cohort study, was conducted. Women ages 30 to 44 years without a history of infertility, early in their attempts to conceive, were followed with standardized pregnancy testing until pregnancy was detected. Medication use was assessed at enrollment, daily for up to 4 months, and then monthly. For this analysis, discrete time regression models were created to calculate the association between antidepressant use and fecundability. Potential confounders-age, body mass index, caffeine, alcohol use, and education-were included in all models. Ninety-two (9.6%) of 957 women reported antidepressant use while attempting to conceive. Women taking antidepressants were more likely to be non-Hispanic Caucasian (91% vs 75%, P Antidepressant use at enrollment had an adjusted fecundability ratio (FR) of 0.86 (95% confidence interval [CI], 0.63-1.20). However, time-varying analyses suggested that antidepressant use in a given cycle is associated with a reduced probability of conceiving in that cycle (adjusted FR, 0.75; 95% CI, 0.53-1.06). After adjusting for history of depression or restricting the analysis to women who reported a history of depression, the association between antidepressant use and decreased fecundability remained [adjusted FR, 0.66 (95% CI, 0.45-0.97) and (adjusted FR, 0.64; 95% CI, 0.43-0.94), respectively]. Our data suggest that antidepressants may reduce the probability of a woman with a history of depression to conceive naturally. Future studies are needed to differentiate the extent to which this association is due to the antidepressant itself

  6. Antidepressants and protein kinases: inhibition of Ca2+-regulated myosin phosphorylation by fluoxetine and iprindole.

    Science.gov (United States)

    Silver, P J; Sigg, E B; Moyer, J A

    1986-02-11

    The effects of several antidepressant and antipsychotic agents on Ca2+-calmodulin-regulated myosin light chain phosphorylation were evaluated. At a concentration of 100 microM, the antidepressant agents buproprion, mianserin and maprotiline were ineffective; zimelidine, desipramine and imipramine produced 40-50% inhibition; and iprindole and fluoxetine produced 75-90% inhibition. The efficacies of iprindole and fluoxetine were similar to the phenothiazine antipsychotics chlorpromazine and trifluoperazine. Clozapine, an atypical antipsychotic and the butyrophenone haloperidol were relatively ineffective as myosin light chain phosphorylation inhibitors. IC50 values of the most effective agents were: trifluoperazine 16 microM, fluoxetine 28 microM, chlorpromazine and iprindole 56 microM. As with trifluoperazine, inhibition of myosin phosphorylation by iprindole was completely attenuated in the presence of exogenous calmodulin. However, a significant component (30%) of the inhibitory effect of fluoxetine was not reversible with calmodulin. These results show that some antidepressant agents, most notably iprindole and fluoxetine, are capable of antagonizing a calmodulin-regulated protein kinase through calmodulin inhibition; and in the case of fluoxetine, through an additional calmodulin-independent mechanism.

  7. Polypharmacy with antidepressants in children and adolescents.

    Science.gov (United States)

    Díaz-Caneja, Covadonga M; Espliego, Ana; Parellada, Mara; Arango, Celso; Moreno, Carmen

    2014-07-01

    The aim of this study was to review current epidemiological data on the use of antidepressants in co-prescription with other psychotropic drugs in children and adolescents, as well as available efficacy and safety information. A Medline search from inception until February 2012 was performed to identify epidemiological and clinical studies, reviews and reports containing potentially relevant information on polypharmacy with antidepressants in young people. There has been an increase in polypharmacy in children and adolescents involving antidepressants in recent years. Antidepressants have become one of the drug classes most frequently prescribed in combination and are commonly co-prescribed with stimulants and antipsychotics. Most information regarding efficacy and safety of polypharmacy patterns was provided by case series and open-label studies. Efficacy studies gave some support for the use of a combination of antidepressants and antipsychotics in the management of refractory obsessive-compulsive disorder and some residual symptoms in major depressive disorder. Even less empirical support was found for a combination of stimulants and antidepressants in co-morbid attention deficit hyperactivity disorder and mood or anxiety disorders. Adverse events were similar to those found with individual medication groups, with severe adverse events mostly reported by individual case reports. The use of polypharmacy with antidepressants has become a regular practice in clinical settings. Although there is still little efficacy and safety information, preliminary evidence points to the potential clinical usefulness of some polypharmacy patterns. Further research on patients with co-morbidities or more severe conditions is needed, in order to improve knowledge of this issue.

  8. Antidepressant use and risk for preeclampsia.

    Science.gov (United States)

    Palmsten, Kristin; Huybrechts, Krista F; Michels, Karin B; Williams, Paige L; Mogun, Helen; Setoguchi, Soko; Hernández-Díaz, Sonia

    2013-09-01

    Prior studies suggest that women who use antidepressants during pregnancy have an increased risk for preeclampsia, yet the comparative safety of specific antidepressants remains unclear. US nationwide Medicaid Analytic eXtract (MAX) data have not been used to study medication safety during pregnancy. We identified 100,942 pregnant women with depression from 2000 to 2007 MAX data. We used pharmacy dispensing records to ascertain exposure to selective serotonin reuptake inhibitor (SSRI), serotonin-norepenephrine reuptake inhibitor (SNRI), tricyclic, bupropion, other antidepressant monotherapy or polytherapy, and specific antidepressants, during the second trimester and first half of the third trimester. Relative risks (RRs) and 95% confidence intervals (CIs) were adjusted for delivery year, preeclampsia risk factors, depression severity proxies, other antidepressant indications, other medications, and healthcare utilization. The risk of preeclampsia was 5.4% among women with depression and no antidepressant exposure. Compared with these women, the risk for preeclampsia was higher among those receiving SNRI (RR: 1.52, 95% CI = 1.26-1.83) and tricyclic monotherapy (RR: 1.62, 95% CI = 1.23-2.12), but not SSRI monotherapy (RR: 1.00, 95% CI = 0.93-1.07) or other antidepressants. Compared with women receiving SSRI monotherapy, preeclampsia risk was higher among women with SNRI (RR: 1.54, 95% CI = 1.28-1.86) and tricyclic (RR: 1.64, 95% CI = 1.25-2.16) monotherapy. None of the specific SSRIs was associated with preeclampsia. The RR with venlafaxine was 1.57 (95% CI = 1.29-1.91) and with amitriptyline 1.72 (95% CI = 1.24-2.40). In this population, SNRIs and tricyclics were associated with a higher risk of preeclampsia than SSRIs.

  9. Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants

    Directory of Open Access Journals (Sweden)

    Caroline Ann Browne

    2013-12-01

    Full Text Available Newer antidepressants are needed for the many individuals with major depressive disorder that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine’s effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse

  10. Antidepressants and colorectal cancer: A population-based nested case-control study.

    Science.gov (United States)

    Lee, Hsiu-Chiung; Chiu, Wei-Che; Wang, Tsu-Nai; Liao, Yin-To; Chien, I-Chia; Lee, Yena; McIntyre, Roger S; Chen, Pau-Chung; Chen, Vincent Chin-Hung

    2017-01-01

    Experimental evidence indicates that serotonin is associated with both proliferative and pro-carcinogenic effects on colorectal tumors. The present study aims to investigate the associations between antidepressant use and colorectal cancer in an epidemiological sample. We conducted a population-based case-control study utilizing Taiwan's National Health Insurance Research Database (NHIRD). We identified 49,342 cases with colorectal cancer and 240,985 controls between 1997 and 2008. We conducted conditional logistic regression analyses to assess the association between antidepressant use and colorectal cancer risk. Sensitivity analyses were conducted to assess whether genotoxic antidepressants (i.e. antidepressants which may exert procarcinogenic effects) would increase risk for colorectal cancer. Selective serotonin reuptake inhibitors (adjusted OR=1.00, 95% CI=0.94-1.06), tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and serotonin antagonist and reuptake inhibitors were not associated with increased incidence of colorectal cancer. Monoamine oxidase inhibitors were, however, associated with an increased incidence of colorectal cancer (adjusted OR=1.22, 95% CI=1.06-1.41). Higher cumulative dose of mirtazapine was associated with a decreased incidence of colorectal cancer (adjusted OR=0.39, 95% CI=0.17-0.90). A small sample size of individuals who received mirtazapine, however, precludes definitive conclusions regarding protective effects with mirtazapine. We could not discern the effects of obesity and other risk factors for colorectal cancer from the NHIRD. Contemporary first-line antidepressants (i.e. SSRI, SNRI), as well as older agents (i.e. TCA), are not associated with increased incidence of colorectal cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Antidepressants reduce neuroinflammatory responses and astroglial alpha-synuclein accumulation in a transgenic mouse model of Multiple System Atrophy

    Science.gov (United States)

    Valera, Elvira; Ubhi, Kiren; Mante, Michael; Rockenstein, Edward; Masliah, Eliezer

    2014-01-01

    Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the pathological accumulation of alpha-synuclein (α-syn) within oligodendroglial cells. This accumulation is accompanied by neuroinflammation with astrogliosis and microgliosis, that leads to neuronal death and subsequent parkinsonism and dysautonomia. Antidepressants have been explored as neuroprotective agents as they normalize neurotrophic factor levels, increase neurogenesis and reduce neurodegeneration, but their anti-inflammatory properties have not been fully characterized. We analyzed the anti-inflammatory profiles of three different antidepressants (fluoxetine, olanzapine and amitriptyline) in the MBP1-hα-syn transgenic (tg) mouse model of MSA. We observed that antidepressant treatment decreased the number of α-syn-positive cells in the basal ganglia of 11-month old tg animals. This reduction was accompanied with a similar decrease in the colocalization of α-syn with astrocyte markers in this brain structure. Consistent with these results, antidepressants reduced astrogliosis in the hippocampus and basal ganglia of the MBP1-hα-syn tg mice, and modulated the expression levels of key cytokines that were dysregulated in the tg mouse model, such as IL-1β. In vitro experiments in the astroglial cell line C6 confirmed that antidepressants inhibited NF-κB translocation to the nucleus and reduced IL-1β protein levels. We conclude that the anti-inflammatory properties of antidepressants in the MBP1-hα-syn tg mouse model of MSA might be related to their ability to inhibit α-syn propagation from oligodendrocytes to astroglia and to regulate transcription factors involved in cytokine expression. Our results suggest that antidepressants might be of interest as anti-inflammatory and α-syn-reducing agents for MSA and other α-synucleinopathies. PMID:24310907

  12. Antidepressant use in children and adolescents diagnosed with major depressive disorder: what can we learn from published data?

    Science.gov (United States)

    Gentile, Salvatore

    2010-01-01

    The consequences of major depression disorder (MDD) in youths are likely to be devastating for both the patient and his/her family. Thus, this review analyzes systematically the effectiveness of antidepressant drugs (ADDs) in managing such patients. Medical literature reporting primary data on use of ADDs in children and adolescents was identified through searches (1966-January 2010) of MEDLINE/PubMed, EMBASE, SCOPUS, and The Cochrane Library databases. Additional studies were manually identified from the reference lists of published articles. Search terms (variously combined) were: children, childhood, adolescents, adolescence, MDD, mood/affective disorders, depression, tricyclic antidepressants (TCAs) SSRIs, Serotonin-Norepinephrine Reuptake inhibitors (SNRIs), noradrenergic/specific serotoninergic antidepressants (NaSSA). A separate search was conducted to complete the profile of effectiveness of each single antidepressant agent. 43 peer-reviewed articles met the inclusion criteria. Reviewed information does not definitively support the use of antidepressants in children younger than 10 years old. In contrast, robust information suggests that fluoxetine should be considered as first-line agent in depressed adolescents whose clinical conditions require psychopharmacological approach. Depressed children should be primarily approached with non-pharmacological interventions that should include the evaluation of potential parental psychiatric disorders. In adolescents with MDD, the decision to use fluoxetine should be associated with specific social and health protocols focused to reinforce self-esteem, improve the quality of relationships with parents and peers, facilitate healthy life-style changes, and identify the potential onset/worsening of suicidality.

  13. Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr

    2010-01-01

    Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The curren...... study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients....

  14. Meta-analysis: Risk of dry mouth with second generation antidepressants.

    Science.gov (United States)

    Cappetta, Kiley; Beyer, Chad; Johnson, Jessica A; Bloch, Michael H

    2017-12-20

    The goal of this meta-analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment-induced dry mouth. A PubMed search was conducted to identify double-blind, randomized, placebo-controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD. A random-effects meta-analysis was used to quantify the pooled risk ratio of treatment-emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta-regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth. 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR)=2.24, 95% Confidence Interval (CI): 1.95-2.58, z=11.2, pz=5.8, pz=10.32, pz=5.85, pz=3.26, p=0.001) and Alpha-2 (PE=0.49, 95% CI: 0.22-0.75, z=3.64, pz=2.10, p<0.05) was significantly associated with increased risk of dry mouth. The current meta-analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs. Copyright © 2017. Published by Elsevier Inc.

  15. Antidepressant stimulation of CDP-diacylglycerol synthesis does not require monoamine reuptake inhibition

    Directory of Open Access Journals (Sweden)

    Aboukhatwa Marwa A

    2010-01-01

    Full Text Available Abstract Background Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol. Results Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues. Conclusion Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence

  16. Antidepressant medication and the risk of pregnancy-induced hypertension

    NARCIS (Netherlands)

    Ter Heijne, Loes F.; Zakiyah, Neily; Bos, Jens H.J.; Hak, Eelko; Schuiling-Veninga, Catharina C.M.

    2016-01-01

    Background: Increased activity of the sympatic nervous system could possibly cause pregnancy-induced hypertension (PIH). Previous studies have suggested that antidepressants could contribute to this increased activity. Objectives: To examine whether the use of antidepressants during pregnancy

  17. Chirality of Modern Antidepressants: An Overview

    Directory of Open Access Journals (Sweden)

    Monica Budău

    2017-12-01

    Full Text Available The majority of modern antidepressants (selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors have one or two centers of asymmetry in their structure; resulting in the formation of enantiomers which may exhibit different pharmacodynamic and pharmacokinetic properties. Recent developments in drug stereochemistry has led to understanding the role of chirality in modern therapy correlated with increased knowledge regarding the molecular structure of specific drug targets and towards the possible advantages of using pure enantiomers instead of racemic mixtures. The current review deals with chiral antidepressant drugs; presenting examples of stereoselectivity in the pharmacological actions of certain antidepressants and their metabolites and emphasizing the differences between pharmacological actions of the racemates and pure enantiomers.

  18. Nitric Oxide Synthase Inhibitors as Antidepressants

    Directory of Open Access Journals (Sweden)

    Vallo Volke

    2010-01-01

    Full Text Available Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression.

  19. Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

    Directory of Open Access Journals (Sweden)

    Eleni Paizanis

    2007-01-01

    Full Text Available There is a growing body of evidence that neural stem cells reside in the adult central nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone, where it is controlled by several trophic factors and neuroactive molecules. Neurogenesis is involved in processes such as learning and memory and accumulating evidence implicates hippocampal neurogenesis in the physiopathology of depression. We herein review experimental and clinical data demonstrating that stress and antidepressant treatments affect neurogenesis in opposite direction in rodents. In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs supports the view that neuroplastic phenomena are involved in the physiopathology of depression and underlie—at least partly—antidepressant therapy.

  20. [Modification of sexual functions by antidepressants].

    Science.gov (United States)

    Baier, D; Philipp, M

    1994-01-01

    Sexual dysfunctions appear to be frequently occurring adverse events in treatment with antidepressants. Due to methodological reasons, a reliable estimation of the frequency of such events is currently not yet possible. There is evidence, that antidepressants could be differentiated with respect to their potency and specificity for disturbances of certain sexual subfunctions according to their pharmacological profile. With SSRIs in particular impaired functions of orgasm and ejaculation can be observed. No deteriorations are reported for buproprion and an improvement of sexual dysfunctions within the course of treatment for moclobemide. Viloxazine and trazodone appear to possess marked stimulating effects on libido and erectile functions. Generally the incidence of sexual adverse events is underestimated, although there is a pronounced impact on patient compliance. Taking into account this well documented side effect, sexual impairments should be monitored carefully within antidepressive treatment.

  1. Potential of Glutamate-Based Drug Discovery for Next Generation Antidepressants

    Directory of Open Access Journals (Sweden)

    Shigeyuki Chaki

    2015-09-01

    Full Text Available Recently, ketamine has been demonstrated to exert rapid-acting antidepressant effects in patients with depression, including those with treatment-resistant depression, and this discovery has been regarded as the most significant advance in drug development for the treatment of depression in over 50 years. To overcome unwanted side effects of ketamine, numerous approaches targeting glutamatergic systems have been vigorously investigated. For example, among agents targeting the NMDA receptor, the efficacies of selective GluN2B receptor antagonists and a low-trapping antagonist, as well as glycine site modulators such as GLYX-13 and sarcosine have been demonstrated clinically. Moreover, agents acting on metabotropic glutamate receptors, such as mGlu2/3 and mGlu5 receptors, have been proposed as useful approaches to mimicking the antidepressant effects of ketamine. Neural and synaptic mechanisms mediated through the antidepressant effects of ketamine have been being delineated, most of which indicate that ketamine improves abnormalities in synaptic transmission and connectivity observed in depressive states via the AMPA receptor and brain-derived neurotrophic factor-dependent mechanisms. Interestingly, some of the above agents may share some neural and synaptic mechanisms with ketamine. These studies should provide important insights for the development of superior pharmacotherapies for depression with more potent and faster onsets of actions.

  2. [Depression and treatment. Apoptosis, neuroplasticity and antidepressants].

    Science.gov (United States)

    Arantes-Gonçalves, Filipe; Coelho, Rui

    2006-01-01

    Depression's neurobiology begins to be better understood. The last decade data considers neuroplasticity and stress as implicated factors on the pathophisiology of depression. Because antidepressants have a lag-time on their action it is possible that inhibition of neurotransmitters recaptation is not sufficient to explain long term changes. For that purpose, neurogenesis increase, nervous fibers sprouting, new synapses and stabilization of the old ones can be responsible for those changes. AMPc-MAPcinases-CREB-BDNF cellular cascade can play a significant role in the mechanisms of dendritic restructuration, hippocampal neurogenesis increase and nervous cells survival. The aim of this article is to discuss if apoptosis could play a key role as an ethiopathogenic factor on the patogenesis of depression. It was done a medline search for references with apoptosis, stress, neuroplasticity, depression and antidepressants key-words. It were found 101 original or review references about these subjects. Stress plays a key role in the etiopathogeny of depression. Its deletery effects on apoptosis and neuroplasticity can be changed by antidepressants. Neurogenesis' increase is necessary for their action. This increase is reached with chronic antidepressant treatment and not with other psychotropic drugs which means some pharmacological specificity of antidepressants. AMPc, CREB, BDNF and Bcl-2 can be considered as target genes in antidepressant synthesis. At the level of this neurotrophic factors apoptosis might be included in the neuroplastic model of depression and play a prominent role in etiopathogeny of depression. To confirm that, we need more research on the field to know which are the mechanisms that trigger apoptosis and its biological significance. In relation to the last one, we can say that is possible to be physiological apoptosis in deteriorated neurons death which cannot make strong connections and pathological apoptosis because of stress via, namely, HPA axis.

  3. Pharmaco-Epidemiological Studies on Antidepressant Use in Older Adults

    NARCIS (Netherlands)

    R. Noordam (Raymond)

    2015-01-01

    markdownabstract__Abstract__ With the increasing number of patients using antidepressants, the number of patients at risk to develop antidepressant-associated adverse drug reactions is also increasing. However, there were not much studies conducted on antidepressant safety in older adults,

  4. COMPARISON OF ANTIDEPRESSANT ACTIVITY OF LOSARTAN WITH IMIPRAMINE IN ALBINO MICE

    Directory of Open Access Journals (Sweden)

    Choppadandi

    2016-06-01

    Full Text Available OBJECTIVES Comparison of antidepressant activity of Losartan with Imipramine in albino mice. BACKGROUND Of all the afflictions that trouble the soul, depression is the commonest characterised by a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Similarly, hypertension is another condition which has emerged as a major public health problem in India and many other developing countries. There is compulsion that 35% of the population has to use the antihypertensives and antidepressants simultaneously for a long period of time to maintain their health. The present work is aimed at comparing antidepressant activity of losartan with imipramine which acts by raising brain BDNF (Brain derived neurotrophic factor levels so that a single agent can be used for both the conditions avoiding multiple medications. METHOD 18 Albino mice were taken, divided into 6 mice in each group and subjected to Forced swim test. All the drugs were administered orally. Drugs were administered and time of onset of immobility is measured 60 min. after the drug administration along with total duration of immobility. Animals are exposed to pretest of 15 min., 24 hrs. prior to the 6 min. swim test. Each animal is considered immobile when it ceased to struggle and swim and remained floating in the water, only moving to keep its head above water. Control group received distilled water (10 mL/kg. Standard group received Imipramine (5 mg/kg and test group was treated with Losartan (3 mg/kg. The Forced swim test for each mouse was video captured which was later analysed to count the time of onset of immobility and total duration of immobility. RESULTS Data was analysed using Analysis of Variance (ANOVA. Losartan showed significant antidepressant activity indicated by significant delay (P<0.05 in the time of onset of immobility and significant reduction (P<0.05 in the total duration of immobility compared to

  5. Dealing With Depression: Antidepressant Skills for Teens

    OpenAIRE

    Bilsker, Dan; Gilbert, Merv; Worling, David; Garland, Jane

    2005-01-01

      Dealing with Depression is a workbook for teens that explains depression and teaches three main antidepressant skills you can use to help overcome or prevent it. The skills are presented in a step-by-step way so that you may learn them easily and apply them to your life. Sometimes these antidepressant skills can be used on their own, when the mood problem isn't too severe, and sometimes they have to be used along with treatments prescribed by professionals. Either way, practicing th...

  6. Poisoining with Tricyclic Antidepressants and Current Treatment

    Directory of Open Access Journals (Sweden)

    Muge Gulen

    2016-12-01

    Full Text Available Poisoning with tricyclic antidepressants is one of the main causes of morbidity and mortality compared to all the antidepressants. Main toxic effects are on the cardiovascular system and central nervous system and manifests itself as anticholinergic symptoms. There is no antidote known to be used in the treatment. But sodium bicarbonate treatment is effective in preventing ventricular arrhythmias and hypotension, and resolving metabolic acidosis. There are some treatments that has been used for relief of symptoms and some of them still are in research stage. The drugs that are used can be customized according to the patients symptoms. [Archives Medical Review Journal 2016; 25(4.000: 608-621

  7. Enhancement of antinociceptive effect of morphine by antidepressants in diabetic neuropathic pain model.

    Science.gov (United States)

    Cegielska-Perun, Krystyna; Bujalska-Zadrożny, Magdalena; Gąsińska, Emilia; Makulska-Nowak, Helena Elżbieta

    2014-04-01

    Recent studies have shown that influence of antidepressants on analgesic action of opioids is heterogeneous. The aim of this study was to investigate the effect of acute and repeated (21 days) antidepressant (amitriptyline, moclobemide and reboxetine) treatment on the antinociceptive action of morphine, an opioid agonist, in streptozotocin (STZ)-induced neuropathic pain model. The studies were performed on the male Wistar rats. The changes in nociceptive thresholds were determined by using mechanical stimuli (the Randall-Selitto and the von Frey tests). Diabetes was induced by intramuscular administration of STZ. In this work we report that acute as well as repeated per os administration of antidepressants (amitriptyline, moclobemide and reboxetine) significantly potentiated the antihyperalgesic effect of morphine in STZ-induced neuropathic pain model. Combination therapy, such as classical antidepressants (amitriptyline, moclobemide) with opioids, or agents with noradrenaline reuptake inhibition and μ-opioid receptor activation could be a new target for research into treatment of painful diabetic neuropathy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Is the antidepressive effect of second-generation antidepressants a myth?

    DEFF Research Database (Denmark)

    Bech, P

    2010-01-01

    Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of approximately 0.30 in favour...... of antidepressants in the acute therapy of major depression. The clinical significance of an effect size at this level was found to be so poor that these meta-analyses have subscribed to the myth of an exclusively placebo-like effect of second-generation antidepressants. A re-allocation of HAMD items focusing...... on those items measuring severity of clinical depression, the HAMD6, has identified effect sizes of >or=0.40 for second-generation antidepressants in placebo-controlled trials for which even a dose-response relationship can be demonstrated. In the relapse-prevention phase during continuation therapy...

  9. Antidepressant properties of aqueous acerate from Gladiolus ...

    African Journals Online (AJOL)

    Materials and Methods: We assessed the antidepressant properties of G. dalenii corm aqueous extract in mice, using the open field, forced swimming, and tail suspension tests. Spontaneous locomotor activity of mice given various doses of G. dalenii extract (per os) was determined in the open field, whereas immobility was ...

  10. Physiological Bases of Bulimia, and Antidepressant Treatment.

    Science.gov (United States)

    Getzfeld, Andrew R.

    This paper reviews the literature on the physiological causes of bulimia and investigates the rationale behind the usage of antidepressant medication in the treatment of bulimia nervosa. No definite conclusions can be stated regarding the physiology of bulimia, but a number of hypotheses are suggested. It appears that the hypothalamus is involved…

  11. Tricyclic antidepressant overdose necessitating ICU admission ...

    African Journals Online (AJOL)

    Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1 000 ng/ml were associated ...

  12. Mind your state: Insights into antidepressant nonadherence ...

    African Journals Online (AJOL)

    Major depressive disorder (MDD) is an insidious disease and affects up to 15% of the global population. Although MDD responds to a wide range of pharmacological treatment options, a number of factors, i.e. not adhering to treatment for at least 4–12 months, contribute to antidepressants not being highly effective.

  13. Effects of antidepressant drugs on sexual function.

    Science.gov (United States)

    Baldwin, D S; Thomas, S C; Birtwistle, J

    1997-01-01

    Adequate sexual expression is an essential part of human relationships, enhancing quality of life and providing a sense of physical, psychological and social well-being. Unfortunately, depression is associated with impairments of sexual function and satisfaction. These problems can worsen a quality of life that is already reduced by the effects of depressive illness. The existing antidepressant drugs are far from ideal, most having adverse effects on sexual function. Unfortunately, the exact incidence of sexual dysfunction during treatment with many antidepressants is not known. Disturbances of sexual interest and performance will only be detected in a reliable fashion when systematic enquiries are made during the course of the standard clinical interview. Growing awareness of the adverse effects of many antidepressants on sexual function has led to some re-evaluation of the earlier claims for the good tolerability of many of the newer drugs. There is a clear need for further well-designed controlled studies of the effects of antidepressants on sexual function, so that this aspect of the tolerability of differing drugs can be assessed more reliably. (IntJ Psych Clin Pract 1997; 1: 47-58).

  14. Anti-Depressants, Suicide, and Drug Regulation

    Science.gov (United States)

    Ludwig, Jens; Marcotte, Dave E.

    2005-01-01

    Policymakers are increasingly concerned that a relatively new class of anti-depressant drugs, selective serotonin re-uptake inhibitors (SSRI), may increase the risk of suicide for at least some patients, particularly children. Prior randomized trials are not informative on this question because of small sample sizes and other limitations. Using…

  15. Antidepressant screening and flavonoids isolation from ...

    African Journals Online (AJOL)

    Eremostachys laciniata (L) Bunge (Lamiaceae), a rich source of flavonoids, has been investigated for chemical constituents and in vivo antidepressant property using forced swim test (FST) model. Five important compounds were isolated, including luteolin (1), apigenin (2), 5,8-dihydroxy-6,7- dimethoxyflavone (3), 5 ...

  16. ANTIDEPRESSANT THERAPY IN HIGH-RISK PATIENTS

    African Journals Online (AJOL)

    Table II pertains to important considerations regarding the moice of antidepressant therapy in patients with hepatic impairment, i.e. the possible risk of hepatotoxicity and the potential need for dosage adjustment. An increased susceptibility to the sedative effects of psychotropic drugs has been described in cirrhotic patients,.

  17. Antidepressant utilization after hospitalization with depression

    DEFF Research Database (Denmark)

    Wallach-Kildemoes, Helle; Thomsen, Louise Thirstrup; Kriegbaum, Margit

    2014-01-01

    Background: Antidepressant (AD) therapy is recommended for patients 4-12months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD ther...

  18. Hyperforin: A lead for antidepressants | Hussain | International ...

    African Journals Online (AJOL)

    Hyperforin: A lead for antidepressants. S Hussain, Z Ansari, M Arif. Abstract. Depression is a complex but treatable disorder if diagnosed appropriately. However, despite the advances in the understanding of the molecular basis of this disorder and the vast range of medication, psychotherapy and electroconvulsive therapy, ...

  19. Tritiation of unsaturated tricyclic antidepressants for radioimmunoassay

    International Nuclear Information System (INIS)

    Buchman, O.; Azran, J.; Shimoni, M.

    1983-01-01

    A rapid and convenient method to obtain specific an high activity tritium labelling of tricyclic antidepressants which have a double bond, is described. The procedure is based on the halogenation of the active benzylic positions of the unlabelled material and the selective catalytic removal of the halogen atom by tritium in the presence of a base which inhibits the attack on the olefin bond

  20. Antidepressant induced sexual dysfunction Part 1: epidemiology ...

    African Journals Online (AJOL)

    Adele

    Part 2 will focus on the assessment and management of AISD. Antidepressant induced sexual dysfunction Part 1: epidemiology and clinical presentation .... Poor self esteem. SOCIAL. Cultural issues. Religious issues. Environmental issues. Interpersonal conflicts. Partner specific. Sexual activity specific. Pregnancy and ...

  1. Response to tricyclic antidepressants: independent of gender?

    NARCIS (Netherlands)

    Wohlfarth, Tamar; Storosum, Jitschak G.; Elferink, André J. A.; van Zwieten, Barbara J.; Fouwels, Annemarie; van den Brink, Wim

    2004-01-01

    OBJECTIVE: The authors examined gender differences in response to tricyclic antidepressants. METHOD: A total of 30 randomized, placebo-controlled trials that included 3,886 patients (1,555 men and 2,331 women), submitted between 1979 and 1991 in order to obtain marketing authorization, were

  2. Jieyuanshen decoction exerts antidepressant effects on depressive ...

    African Journals Online (AJOL)

    Conclusion: JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter. Keywords: Hypothalamic-pituitary-adrenal (HPA) axis; Glucocorticoid/ ...

  3. Antidepressant-like effects of an alkaloid extract of the aerial parts of Annona cherimolia in mice.

    Science.gov (United States)

    Martínez-Vázquez, M; Estrada-Reyes, R; Araujo Escalona, A G; Ledesma Velázquez, I; Martínez-Mota, L; Moreno, J; Heinze, G

    2012-01-06

    Several species of Annona (Annonaceae) are used in traditional Mexican medicine by their anti-anxiety, anticonvulsant and tranquilizing properties. It has been reported that the alkaloids isolated from some species of the Annona have affinity to serotonergic 5-HT(1A) receptors and modulate dopaminergic transmission, which is involved in depressive disorders. To investigate the antidepressant-like effect of an alkaloid extract from the aerial parts of Annona cherimola (TA) in mice. The antidepressant-like effect was evaluated in the forced swimming test. To elucidate a possible mechanism of action, experiments of synergism with antidepressant drugs, such as imipramine (IMI), clomipramine (CLIMI), and fluoxetine (FLX), were carried out. The neurotransmitter content (DA: dopamine, 5HT: serotonin and its metabolites, HVA: homovanillic acid and 5HIAA: 5-hydroxyindoleacetic) in the whole brain of mice were also determined by HPLC method. TA chemical composition was determined using high performance liquid chromatography-electrospray mass spectrometry. The results showed that repeated treatment with TA produced antidepressant-like effects in mice. This effect was not related to an increase in locomotor activity. Administration of TA facilitated the antidepressant effect of IMI and CLIMI as well as increased the turnover of DA and 5-HT. The alkaloids: 1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzoquinoline-3,8,9,10-tetraol, anonaine, liriodenine, and nornuciferine were the main constituents of TA. Results showed that TA produces an antidepressant-like action from a generalized increase in monominergic turnover, supporting the use in tradicional medicine of Annona cherimolia, and strongly suggest its therapeutic potency as an antidepressant agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness.

    Science.gov (United States)

    Macedo, Danielle; Filho, Adriano José Maia Chaves; Soares de Sousa, Caren Nádia; Quevedo, João; Barichello, Tatiana; Júnior, Hélio Vitoriano Nobre; Freitas de Lucena, David

    2017-01-15

    The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs. A discussion regarding the possible contribution of the antimicrobial effect of antidepressant drugs to its effectiveness/resistance is included. The search included relevant articles from PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge. MDD is associated with changes in gut permeability and microbiota composition. In this respect, antidepressant drugs present antimicrobial effects that could also be related to the effectiveness of these drugs for MDD treatment. Conversely, some antimicrobials present antidepressant effects. Both antidepressants and antimicrobials present neuroprotective/antidepressant and antimicrobial effects. Further studies are needed to evaluate the participation of antimicrobial mechanisms of antidepressants in MDD treatment as well as to determine the contribution of this effect to antidepressant resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve.

    Science.gov (United States)

    Hung, Yu-Chun; Suzuki, Suzuko; Huang, Chun-Jen; Chen, Chien-Chuan; Pan, Yu-Yen; Wang, Chi-Fei; Srinavasan, Venkatesh; Gerner, Peter

    2010-07-01

    Current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. Recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block. Rats were anesthetized with isoflurane, and 0.2 mL of amitriptyline, doxepin, or fluoxetine was deposited next to the surgically exposed sciatic nerves (n = 8 per group). Some animals received a second injection containing RTX (n = 8 per group). The effect of nerve block was assessed by neurobehavioral tests of the motor function (extensor postural thrust) and the nocifensive reaction (mechanical pinch). A single application of RTX produced nociceptive-selective sciatic nerve block, whereas antidepressants produced nociceptive and motor block. The combined administration of RTX and antidepressant resulted in a predominantly nociceptive nerve block. Compared with antidepressants or RTX alone, the combination prolonged the nociceptive nerve block more than the motor block. The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.

  6. Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

    Science.gov (United States)

    2011-01-01

    Background After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment. The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode. Methods SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents

  7. The efficacy of primary care chaplaincy compared with antidepressants: a retrospective study comparing chaplaincy with antidepressants.

    Science.gov (United States)

    Macdonald, Gordon

    2017-07-01

    Aim To determine the effectiveness of primary care chaplaincy (PCC) when used as the sole intervention, with outcomes being compared directly with those of antidepressants. This was to be carried out in a homogenous study population reflective of certain demographics in the United Kingdom. Increasing numbers of patients are living with long-term conditions and 'modern maladies' and are experiencing loss of well-being and depression. There is an increasing move to utilise non-pharmacological interventions such as 'talking therapies' within this context. Chaplaincy is one such 'talking therapy' but within primary care its evidence base is sparse with only one quantitative study to date. There is therefore a need to evaluate PCC excluding those co-prescribed antidepressants, as this is not evidenced in the literature as yet. PCC also needs to be directly compared with the use of antidepressants to justify its use as a valid alternative treatment for loss of well-being and depression. This was a retrospective observational study based on routinely collected data. There were 107 patients in the PCC group and 106 in the antidepressant group. Socio-demographic data were collected. Their pre- and post-intervention (either chaplaincy or antidepressant) well-being was assessed, by the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) which is a validated Likert scale. Findings The majority of both groups were female with both groups showing marked ethnic homogeneity. PCC was associated with a significant and clinically meaningful improvement in well-being at a mean follow-up of 80 days. This treatment effect was maintained after those co-prescribed antidepressants were removed. PCC was associated with an improvement in well-being similar to that of antidepressants with no significant difference between the two groups.

  8. Use of Antidepressants During Pregnancy?: What to Consider when Weighing Treatment with Antidepressants Against Untreated Depression.

    Science.gov (United States)

    Muzik, Maria; Hamilton, Susan E

    2016-11-01

    Introduction Mood disorders impact many pregnant women, particularly those who have experienced symptoms prior to conception, and there are significant barriers, including stigma and access, to seeking and receiving appropriate treatments. Antidepressants are a helpful option in treating perinatal depression, but research on risks and benefits of antidepressant use in pregnancy is difficult given lack of "gold standard" comparative trials. Methods This paper summarizes current state of knowledge on the safety of antidepressants during pregnancy by providing a summary of the literature published in the past 3 years (January 2013-October 2015). We identified 21 reviews and meta-analyses that were included in this summary report. This report is meant to provide a user-friendly, yet comprehensive guide summarizing the abundant, and in part contradicting, literature on risks and benefits of antidepressants during pregnancy, in order to assist busy primary care prescribers in educating their patients. Our goal is also to contrast the risks/benefits of untreated depression in pregnancy versus treatment with antidepressant medication in pregnancy, and in such support prescribers in their decision-making. Results The past 3 years have yielded an abundance of publications on the topic, in part, with conflicting findings adding to confusion and concern among providers, patients, and their families. Many reported studies have methodological problems limiting their impact. Data on adverse effects of medications on pregnancy and fetal outcomes have to be weighed against the impact of untreated illness and poor health habits associated with untreated illness on the same outcomes. Discussion Medical-decision making is often complex and seldom free of risks. Obviously, as providers we cannot guarantee that fetal exposure to antidepressants is totally free of risk, yet this is true for any medicine taken in pregnancy. However, to date, perinatal psychiatry has collected enough

  9. Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?

    Directory of Open Access Journals (Sweden)

    Ioannidis John PA

    2008-05-01

    Full Text Available Abstract Antidepressants, in particular newer agents, are among the most widely prescribed medications worldwide with annual sales of billions of dollars. The introduction of these agents in the market has passed through seemingly strict regulatory control. Over a thousand randomized trials have been conducted with antidepressants. Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of "positive" trials (both pre-approval and post-approval. However, two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. I discuss how the use of many small randomized trials with clinically non-relevant outcomes, improper interpretation of statistical significance, manipulated study design, biased selection of study populations, short follow-up, and selective and distorted

  10. H1-histamine receptor affinity predicts weight gain with antidepressants.

    Science.gov (United States)

    Salvi, Virginio; Mencacci, Claudio; Barone-Adesi, Francesco

    2016-10-01

    Weight gain and metabolic abnormalities are extensively found in patients taking psychotropic medications. Although mainly antipsychotics have been implicated, also antidepressants carry the potential to induce weight gain, with tricyclics and mirtazapine being associated with the greatest weight gain. It has been suggested that this could be due to the different ability of antidepressants to block adrenergic, cholinergic, and histaminergic postsynaptic receptors. To date, however, the link between antidepressant-induced weight gain and their receptor affinity profile has not been established. We reanalysed data from a previous meta-analysis to evaluate whether weight change is associated with specific receptor affinity of antidepressants. We retrieved data from the only meta-analysis that assessed weight change with antidepressants. We searched in the Psychoactive Drug Screening Program (PDSP) Ki database data on the affinities of antidepressants to receptors hypothetically linked with weight change: H1-histamine, 5HT2c, M3-muscarinic, and α1A-adrenergic receptors. The association between weight change and receptor affinities was estimated using meta-regression. We found a significant association between the affinity of antidepressants to H1-receptor and weight gain (p value: antidepressants. These results further stress a reclassification of antidepressants according to their pharmacodynamic properties, and suggest avoiding prescribing antidepressants with an anti-histaminergic profile to patients at risk for cardio-metabolic disturbances. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  11. Antidepressant Use and Cognitive Decline: The Health and Retirement Study.

    Science.gov (United States)

    Saczynski, Jane S; Rosen, Allison B; McCammon, Ryan J; Zivin, Kara; Andrade, Susan E; Langa, Kenneth M; Vijan, Sandeep; Pirraglia, Paul A; Briesacher, Becky A

    2015-07-01

    Depression is associated with cognitive impairment and dementia, but whether treatment for depression with antidepressants reduces the risk for cognitive decline is unclear. We assessed the association between antidepressant use and cognitive decline over 6 years. Participants were 3714 adults aged 50 years or more who were enrolled in the nationally representative Health and Retirement Study and had self-reported antidepressant use. Depressive symptoms were assessed using the 8-item Center for Epidemiologic Studies Depression Scale. Cognitive function was assessed at 4 time points (2004, 2006, 2008, 2010) using a validated 27-point scale. Change in cognitive function over the 6-year follow-up period was examined using linear growth models, adjusted for demographics, depressive symptoms, comorbidities, functional limitations, and antidepressant anticholinergic activity load. At baseline, cognitive function did not differ significantly between the 445 (12.1%) participants taking antidepressants and those not taking antidepressants (mean, 14.9%; 95% confidence interval, 14.3-15.4 vs mean, 15.1%; 95% confidence interval, 14.9-15.3). During the 6-year follow up period, cognition declined in both users and nonusers of antidepressants, ranging from -1.4 change in mean score in those with high depressive symptoms and taking antidepressants to -0.5 change in mean score in those with high depressive symptoms and not taking antidepressants. In adjusted models, cognition declined in people taking antidepressants at the same rate as those not taking antidepressants. Results remained consistent across different levels of baseline cognitive function, age, and duration of antidepressant use (prolonged vs short-term). Antidepressant use did not modify the course of 6-year cognitive change in this nationally representative sample. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Is the antidepressive effect of second-generation antidepressants a myth?

    Science.gov (United States)

    Bech, P

    2010-02-01

    Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of approximately 0.30 in favour of antidepressants in the acute therapy of major depression. The clinical significance of an effect size at this level was found to be so poor that these meta-analyses have subscribed to the myth of an exclusively placebo-like effect of second-generation antidepressants. A re-allocation of HAMD items focusing on those items measuring severity of clinical depression, the HAMD6, has identified effect sizes of >or=0.40 for second-generation antidepressants in placebo-controlled trials for which even a dose-response relationship can be demonstrated. In the relapse-prevention phase during continuation therapy of patients with major depression, the advantage of second-generation antidepressants over placebo was as significant as in the acute therapy phase. To explore a myth is not to deny the facts but rather to re-allocate them.

  13. Antidepressant-Induced Female Sexual Dysfunction.

    Science.gov (United States)

    Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

    2016-09-01

    Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  14. Neurogenesis and the Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

  15. Neurogenesis and The Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

  16. Antidepressant effects of Mentha pulegium in mice

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2016-09-01

    Full Text Available The aim of this study is to investigate the antidepressant effects of Mentha pulegium essential oil in BALB/c mice. Six experimental groups (7 mice each were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving M. pulegium essential oil (50, 75 and 100 mg/kg, immobility duration significantly decreased compared to the control group. M. pulegium (50 and 75 mg/kg resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. M. pulegium essential oil antidepressant effect that may be due to the inhibition of oxidative stress. The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.

  17. Antidepressants are not overprescribed for mild depression.

    Science.gov (United States)

    Simon, Gregory E; Rossom, Rebecca C; Beck, Arne; Waitzfelder, Beth E; Coleman, Karen J; Stewart, Christine; Operskalski, Belinda; Penfold, Robert B; Shortreed, Susan M

    2015-12-01

    To evaluate overprescribing of antidepressant medication for minimal or mild depression. Electronic records data from 4 large health care systems identified outpatients aged 18 years or older starting a new episode of antidepressant treatment in 2011 with an ICD-9 diagnosis of depressive disorder (296.2, 296.3, 311, or 300.4). Patient Health Questionnaire-9 (PHQ-9) depression severity scores at time of treatment initiation were used to examine the distribution of baseline severity and the association between baseline severity and patients' demographic and clinical characteristics. Of 19,751 adults beginning treatment in 2011, baseline PHQ-9 scores were available for 7,051. In those with a baseline score, 85% reported moderate or severe symptoms (PHQ-9 score of 10 or more), 12% reported mild symptoms (PHQ-9 score of 5 to 9), and 3% reported minimal symptoms (PHQ-9 score of less than 5). The proportion reporting minimal or mild symptoms when starting treatment increased with age, ranging from 11% in those under age 65 years to 26% in those aged 65 and older. The proportion with minimal or mild symptoms was also moderately higher among patients living in wealthier neighborhoods and those treated by psychiatrists. Nevertheless, across all subgroups defined by sex, race/ethnicity, prescriber specialty, and treatment history, the proportions with minimal or mild symptoms did not exceed 18%. Secondary analyses, including weighting and subgroup analyses, found no evidence that estimates of baseline severity were biased by missing PHQ-9 scores. In these health systems, prescribing of antidepressant medication for minimal or mild depression is much less common than suggested by previous reports. Given that this practice may sometimes be clinically appropriate, our findings indicate that overprescribing of antidepressants for mild depression is not a significant public health concern. © Copyright 2015 Physicians Postgraduate Press, Inc.

  18. Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression.

    Science.gov (United States)

    Peciña, Marta; Bohnert, Amy S B; Sikora, Magdalena; Avery, Erich T; Langenecker, Scott A; Mickey, Brian J; Zubieta, Jon-Kar

    2015-11-01

    High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD). In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the µ-opioid receptor-selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding. Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced µ-opioid neurotransmission in a network of regions implicated in emotion, stress

  19. Antidepressant induced excessive yawning and indifference

    Directory of Open Access Journals (Sweden)

    Bruno Palazzo Nazar

    2015-03-01

    Full Text Available Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

  20. Antidepressants and Suicide Risk: A Comprehensive Overview

    Directory of Open Access Journals (Sweden)

    Roberto Tatarelli

    2010-08-01

    Full Text Available The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year, with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.

  1. Molecular and cellular mechanisms of antidepressant action.

    Science.gov (United States)

    Sharp, Trevor

    2013-01-01

    A long-standing theory is that brain monoamine signalling is critically involved in the mechanisms of antidepressant drug treatment. Theories on the nature of these mechanisms commenced with ideas developed in the 1960s that the drugs act simply by increasing monoamine availability in the synapse. However, this thinking has advanced remarkably in the last decade to concepts which position that antidepressant drug action on monoamine signalling is just the starting point for a complex sequence of neuroadaptive molecular and cellular changes that bring about the therapeutic effect. These changes include activation of one or more programmes of gene expression that leads to the strengthening of synaptic efficacy and connectivity, and even switching neural networks into a more immature developmental state. It is thought that through this increase in plasticity, key neural circuits within the limbic system are more easily remodelled by incoming emotionally relevant stimuli. This article attempts to bring together previous and current knowledge of antidepressant drug action on monoamine signalling at molecular and cellular levels, and introduces current thinking that these changes interact with neuropsychological processes ultimately to elevate mood.

  2. Sexual dysfunction, depression, and the impact of antidepressants.

    Science.gov (United States)

    Kennedy, Sidney H; Rizvi, Sakina

    2009-04-01

    Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

  3. 13C NMR studies of the molecular flexibility of antidepressants

    International Nuclear Information System (INIS)

    Munro, S.L.; Andrews, P.R.; Craik, D.J.; Gale, D.J.

    1986-01-01

    The solution dynamics of a series of clinically potent antidepressants have been investigated by measuring 13 C NMR relaxation parameters. Correlation times and internal motional rates were calculated from spin-lattice relaxation times and nuclear Overhauser effects for the protonated carbons in mianserin, imipramine-like antidepressants, and amitriptyline-like antidepressants. These data were interpreted in terms of overall molecular tumbling, internal rotations, and inherent flexibility of these structures. Of particular interest was the conformational variability of the tricyclic nucleus of the tricyclic antidepressants, where the data indicated a fivefold difference in mobility of the dimethylene bridge of imipramine-like antidepressants relative to amitriptyline-like compounds. The implications of such a difference in internal motions is discussed in relation to previous NMR studies and to the reported differences in pharmacological activity of these antidepressants

  4. Antidepressants and Driving in Older Adults: A Systematic Review.

    Science.gov (United States)

    Cameron, Duncan H; Rapoport, Mark J

    2016-06-01

    With an increasing number of older drivers who are prescribed antidepressants, the potential consequences of antidepressant use on driving skills in an aging population are becoming a pressing issue. We conducted a systematic review using MEDLINE, targeting articles specifically pertaining to antidepressants and driving in a population or subgroup of older adults (≥ 55 years of age). The search yielded 267 references, nine of which pertained to the effects of antidepressants on driving in older adults. The single experimental study found imipramine to have detrimental effects on highway driving, whereas nefazodone did not. Seven of eight population-based studies reported a significant increased risk of involvement in a collision associated with antidepressant use. Although the studies indicated a negative effect of antidepressants on driving, the epidemiological designs cannot exclude the possibility that the underlying illness, generally major depression, is the culprit.

  5. Use of Antidepressants: Expansion Beyond Depression and Anxiety

    OpenAIRE

    Cascade, Elisa F.; Kalali, Amir H.; Thase, Michael E.

    2007-01-01

    We investigated antidepressant prescriptions and reasons for use. According to our data, the top 10 molecules represent ∼95% of total antidepressant prescriptions for both primary care physicians (PCPs) and psychiatrists. The primary difference between PCPs and psychiatrists was the increased use of buproprion and tricyclics/tetracyclics by psychiatrists. The selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants such as venlafaxine (Effexor) and buproprion (Wellbutri...

  6. Continued antidepressant treatment and suicide in patients with depressive disorder

    DEFF Research Database (Denmark)

    Søndergård, Lars; Lopez, Ana Garcia; Andersen, Per Kragh

    2007-01-01

    1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had...... of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.......Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from...

  7. The mGluR7 allosteric agonist AMN082 produces antidepressant-like effects by modulating glutamatergic signaling.

    Science.gov (United States)

    Bradley, Stefania Risso; Uslaner, Jason M; Flick, Rose B; Lee, Ariel; Groover, Kristina M; Hutson, Peter H

    2012-03-01

    Currently prescribed antidepressants affect the reuptake and/or metabolism of biogenic amines. Unfortunately for patients, these treatments require several weeks to produce significant symptom remission. However, recently it has been found that ketamine, a dissociative anesthetic agent that noncompetitively antagonizes NMDA (N-Methyl-d-aspartic acid) receptors, has rapid antidepressant effects at sub-anesthetic doses in clinically depressed patients. These findings indicate that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. For this reason, other mechanisms influencing glutamatergic functioning have gained interest. For example, the metabotropic glutamate receptor 7 (mGluR7) allosteric agonist AMN082 (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride) has been shown to be effective in the forced swim and tail-suspension test, behavioral assays sensitive to antidepressants. Here we extend the characterization of AMN082 by demonstrating its effects on differential reinforcement of low rates of responding (DRL)-30, another assay sensitive to antidepressants. Furthermore, we show the engagement of glutamatergic signaling by demonstrating the ability of the selective AMPA (2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid) receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione) to reverse the effects of AMN082 in the tail suspension test. In contrast, NBQX failed to reverse the effects of imipramine in the same behavioral test. Finally, we report that behaviorally efficacious doses of AMN082 modulate phosphorylation of AMPA and NMDA receptor subunits in the hippocampus. These results suggest that the antidepressant-like effects of AMN082 are, at least in part, due to modulation of AMPA and NMDA receptor activity. Therefore, our findings confirm the hypothesis that mGluR7 could represent a novel target for treating depression. Copyright © 2011 Elsevier Inc. All rights

  8. Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: a review.

    Science.gov (United States)

    Tuccori, Marco; Testi, Arianna; Antonioli, Luca; Fornai, Matteo; Montagnani, Sabrina; Ghisu, Narcisa; Colucci, Rocchina; Corona, Tiberio; Blandizzi, Corrado; Del Tacca, Mario

    2009-06-01

    There is ongoing debate about the safety of selective serotonin reuptake inhibitors (SSRIs) and other serotonergic/noradrenergic antidepressants when used during pregnancy. This article reviews the available literature on the main safety concerns associated with the use of SSRIs and other serotonergic/noradrenergic antidepressants (serotonin-norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants) during pregnancy. English-language reports of analytical and descriptive studies, including case reports, case series, and meta-analyses, were identified through searches of MEDLINE, EMBASE, and PsycINFO (1966-April 2009). The search terms were fluoxetine, paroxetine, sertraline, Citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, reboxetine, duloxetine, SSRI, SNRI, NaSSA, and NRI in association with depression, pregnancy, prenatal exposure, miscarriage, spontaneous abortion, malformation, in utero exposure, and neonatal complications. Paroxetine has been associated with significant risks of major malformation, particularly cardiac defects, when used during pregnancy. Significant associations between maternal exposure to SSRIs and both persistent pulmonary hypertension of the newborn and a self-limiting neonatal behavioral syndrome have been reported in a number of recent original studies and meta-analyses. Some studies have suggested a relationship between the use of SSRIs or other serotonergic/noradrenergic antidepressants and the occurrence of miscarriage, although these studies had methodologic limitations that affected the strength of the data. Evidence for a possible association between in utero exposure to SSRIs or other serotonergic/noradrenergic antidepressants and alterations in neurobehavioral development, bleeding, and QTc-interval prolongation is currently weak. The available evidence suggests that SSRIs and other serotonergic/noradrenergic antidepressants should be used with

  9. A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression.

    Science.gov (United States)

    Nelson, J Craig; Baumann, Pierre; Delucchi, Kevin; Joffe, Russell; Katona, Cornelius

    2014-10-01

    Lithium augmentation of antidepressants for treatment of unipolar major depression was one of the first adjunctive strategies based on a neuropharmacologic rationale. Randomized controlled trials supported its efficacy but most trials added lithium to tricyclic antidepressants (TCAs). Despite its efficacy, use of lithium augmentation remains infrequent. The current systematic review and meta-analysis examines the efficacy of lithium augmentation as an adjunct to second generation antidepressants as well as to TCAs and considers reasons for its infrequent use. A systematic search of Medline and the Cochrane Clinical Trials database was performed. Randomized, placebo-controlled trials of lithium augmentation were selected. A fixed-effects meta-analysis was performed. Odds ratios for response were calculated for each treatment-control contrast, for the trials grouped by type of initial antidepressant (TCA or second generation antidepressant), and as a meta-analytic summary for all treatments combined. Nine trials that included 237 patients were selected. The odds ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I(2)=0%. Adjunctive lithium was effective with TCAs (7 contrasts) and with second generation agents (3 contrasts). Discontinuation due to adverse events was infrequent and did not differ between lithium and placebo. The meta-analysis is limited by the small size and number of trials and limited data for treatment resistant patients. Adjunctive lithium appears to be as effective for second generation antidepressants as it was for the tricyclics. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Comparing augmentation with non-antidepressants over sticking to antidepressants after treatment failure in depression: a naturalistic study.

    Science.gov (United States)

    Köhler, S; Unger, T; Hoffmann, S; Steinacher, B; Fydrich, T; Bschor, T

    2013-03-01

    Non-response to an antidepressant monotherapy in unipolar depression is quite common. Therefore strategies for subsequent treatment steps are necessary. However, there is a lack of direct comparisons of these different strategies. In this naturalistic study we compared the outcome to different strategies after failure of the primary antidepressant treatment. Failure of primary antidepressant monotherapy occurred in 135 patients. 98 of these patients have been administered 4 treatment strategies of the physicians' choice: lithium augmentation (Li-Augm), switching to another antidepressant (AD-Switch), combination of 2 antidepressants (AD-Comb) or augmentation with second generation antipsychotic (SGA-Augm). Primary outcome measure was the 17-item Hamilton rating scale for depression (HRSD). Patients who received Li-Augm or augmentation with SGAs showed significantly greater improvement in HRSD and BDI compared to patients with antidepressant switch or antidepressant combination. Remission rates for Li-Augm and SGA-Augm were 89.3% and 86.2% compared to 40.7% for AD-Switch and 42.9% for AD-Comb. Changing to another pharmacological class (Li-Augm or augmentation with SGAs) showed better treatment results than sticking to the class of antidepressants (AD-Switch and AD-Comb) after primary failure in response to antidepressant monotherapy in unipolar depression. The lack of randomization and absence of a non-response definition are design flaws. Controlled studies are required to confirm the findings of this trial. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Identifying fast-onset antidepressants using rodent models.

    Science.gov (United States)

    Ramaker, M J; Dulawa, S C

    2017-05-01

    Depression is a leading cause of disability worldwide and a major contributor to the burden of suicide. A major limitation of classical antidepressants is that 2-4 weeks of continuous treatment is required to elicit therapeutic effects, prolonging the period of depression, disability and suicide risk. Therefore, the development of fast-onset antidepressants is crucial. Preclinical identification of fast-onset antidepressants requires animal models that can accurately predict the delay to therapeutic onset. Although several well-validated assay models exist that predict antidepressant potential, few thoroughly tested animal models exist that can detect therapeutic onset. In this review, we discuss and assess the validity of seven rodent models currently used to assess antidepressant onset: olfactory bulbectomy, chronic mild stress, chronic forced swim test, novelty-induced hypophagia (NIH), novelty-suppressed feeding (NSF), social defeat stress, and learned helplessness. We review the effects of classical antidepressants in these models, as well as six treatments that possess fast-onset antidepressant effects in the clinic: electroconvulsive shock therapy, sleep deprivation, ketamine, scopolamine, GLYX-13 and pindolol used in conjunction with classical antidepressants. We also discuss the effects of several compounds that have yet to be tested in humans but have fast-onset antidepressant-like effects in one or more of these antidepressant onset sensitive models. These compounds include selective serotonin (5-HT) 2C receptor antagonists, a 5-HT 4 receptor agonist, a 5-HT 7 receptor antagonist, NMDA receptor antagonists, a TREK-1 receptor antagonist, mGluR antagonists and (2R,6R)-HNK. Finally, we provide recommendations for identifying fast-onset antidepressants using rodent behavioral models and molecular approaches.

  12. Is the antidepressive effect of second-generation antidepressants a myth?

    DEFF Research Database (Denmark)

    Bech, P

    2010-01-01

    Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of approximately 0.30 in favour...

  13. Current and Future Perspectives on the Major Depressive Disorder: Focus on the New Multimodal Antidepressant Vortioxetine.

    Science.gov (United States)

    Orsolini, Laura; Tomasetti, Carmine; Valchera, Alessandro; Iasevoli, Felice; Buonaguro, Elisabetta Filomena; Fornaro, Michele; Fiengo, Annastasia L C; Martinotti, Giovanni; Vellante, Federica; Matarazzo, Ilaria; Vecchiotti, Roberta; Perna, Giampaolo; Nicola, Marco Di; Carano, Alessandro; Bartolomeis, Andrea de; Giannantonio, Massimo Di; Berardis, Domenico De

    2017-01-01

    Vortioxetine (VRX) is a multimodal antidepressant that acts as serotonin (5HT) transporter inhibitor as well as 5HT3A and 5HT7 receptors antagonist, 5HT1A and 5HT1B receptors partial agonist. It was recently approved in the US and the EU for the treatment of adult patients with Major Depressive Disorder (MDD). The present article aims at systematically reviewing findings of the published and unpublished research on the pharmacological properties, efficacy, safety and tolerability of oral VRX in the treatment of MDD. A systematic review, in accordance with the Cochrane Collaboration and the PRISMA guidelines, was conducted searching the electronic databases MEDLINE, by combining the following keyterms: ((vortioxetine OR LU AA21004 OR brintellix) AND (antidepressant OR depression OR major depressive disorder), without language/time restrictions. Further studies were retrieved from reference listing of relevant articles or manual search. Preclinical and clinical studies (RCT and open label trials) were here retrieved. Several placebo-controlled and active-treatment studies demonstrated the antidepressant efficacy and tolerability of VRX in adult patients affected with MDD. In addition, VRX seems to own procognitive activity. VRX seems generally well tolerated, without significant cardiovascular or weight gain effects. The most common adverse events reported included nausea, vomiting, hyperhidrosis, headache, dizziness, somnolence, diarrhoea and dry mouth. Overall, placebo controlled and active treatment trials support that VRX is effective and well tolerated in MDD. Its combined serotonin reuptake inhibition with agonism, partial agonism and antagonism of a number of receptors might provide a broader spectrum of antidepressant activity than currently available agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. [Fatal outcome after overdosage with antidepressants].

    Science.gov (United States)

    Gude, Martin Faurholdt; Jensen, Lisbet Tokkesdal; Bjerre-Kristensen, Lars

    2014-02-10

    Serotonin syndrome (SS) is a complication after overdosage with antidepressants. SS increases the level of circulating serotonin. Fatal outcome of SS is most often seen in cases where there has been an overdosage with selective serotonin reuptake inhibitors (SSRI)/selective noradrenaline reuptake inhibitors (SNRI) in combination with other serotonin increasing drugs. This case report describes the rapid development of symptoms in a 54-year-old man who ingested a total amount of 6.5 g of SSRI and SNRI drugs as the only drug types. It proves the importance of being aware of the symptoms of SS when the patient is first seen in the emergency department.

  15. Evidence for folate in combination with antidepressants at initiation of therapy.

    Science.gov (United States)

    Fava, Maurizio; Mischoulon, David

    2010-11-01

    Although the goal of treatment for major depressive disorder is full remission, for most patients, remission is the exception rather than the rule. Carefully choosing medications with synergistic mechanisms of action at treatment initiation may increase rates of response and remission and decrease the risk for relapse. An agent such as folate, which is a naturally occurring B vitamin and is necessary for the synthesis of the trimonoamine neurotransmitters implicated in depression, may enhance the effects of a traditional antidepressant. © Copyright 2010 Physicians Postgraduate Press, Inc.

  16. Risks for oral health with the use of antidepressants

    NARCIS (Netherlands)

    Peeters, FPML; deVries, MW; Vissink, A

    In this article, attention is focused on ornl pathology, particularly dental caries, caused by hyposalivation as a consequence of (long-term) use of antidepressants. Changes in clinical psychiatric practice and increasing numbers of presciptions of antidepressants in primary care and specialty care

  17. Antidepressants during pregnancy, risks for mother and child

    NARCIS (Netherlands)

    Ververs, F.F.T.

    2009-01-01

    The use of antidepressant drugs during pregnancy is increasing without firm evidence on safety or efficacy. When managing depression and anxiety with antidepressants, the expected benefits must outweigh the risks. For health care processionals it is difficult to balance the benefits against the

  18. Efficacy of antidepressants on orofacial pain: a systematic review

    NARCIS (Netherlands)

    Martin, W.J.J.M.; Perez, R.S.G.M.; Tuinzing, D.B.; Forouzanfar, T.

    2012-01-01

    Orofacial pain is a common complaint with multiple diagnoses. There is controversy about the effectiveness of antidepressants for the management of orofacial pain disorders. In order to be able to make a best evidence choice between available antidepressants for the treatment of orofacial pain, a

  19. Antidepressants for non-specific low back pain

    NARCIS (Netherlands)

    Urquhart, D. M.; Hoving, J. L.; Assendelft, W. W. J. J.; Roland, M.; van Tulder, M. W.

    2008-01-01

    BACKGROUND: Antidepressants are commonly used in the management of low-back pain. However, their use is controversial. OBJECTIVES: The aim of this review was to determine whether antidepressants are more effective than placebo for the treatment of non-specific low-back pain. SEARCH STRATEGY:

  20. nfluence of antidepressants on glucose homeostasis : effects and mechanisms

    NARCIS (Netherlands)

    Derijks, H.J.

    2009-01-01

    Depression has shown to be a common morbidity in patients with diabetes mellitus and comorbid depression in diabetes mellitus patients is frequently treated with antidepressants. It has been postulated that antidepressants may interfere with glucose homeostasis and that the interference of

  1. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia

    OpenAIRE

    Terevnikov, Viacheslav; Joffe, Grigori; Stenberg, Jan-Henry

    2015-01-01

    Background: Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. Methods: To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, ...

  2. Antidepressive interventions : On state and vulnerability of the brain

    NARCIS (Netherlands)

    Korf, J

    An attempt is made to relate drug and non-drug antidepressive interventions to brain processes. In the present context two concepts are proposed: vulnerability towards depressogenic factors and depression as a state of the brain. Accordingly, it is assumed that the current antidepressants make the

  3. Antidepressant induced sexual dysfunction Part 2: assessment and ...

    African Journals Online (AJOL)

    Adele

    the prevalence of antidepressant induced sexual dysfunction and its clinical presentation both generally and in the case of individual classes of antidepressants. ... rates are found with spontaneous self-reporting and higher rates result when ... long sexual functioning compared with the current presentation. A person's ...

  4. Antidepressant prevalence for youths : a multi-national comparison

    NARCIS (Netherlands)

    Zito, J.M.; Tobi, H.; de Jong-van den Berg, L.T.W.; Fegert, J.M.; Safer, D.J.; Janhsen, K.; Hansen, D.G.; Gardner, J.F.; Glaeske, G.

    2006-01-01

    Objective To compare antidepressant prevalence data in youths across three western European countries (Denmark, Germany, and the Netherlands) with US regional data in terms of age and gender and to show proportional subclass antidepressant (ATD) use. Method A population-based analysis of

  5. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression.

    Science.gov (United States)

    Thomas, Samantha J; Shin, Mirae; McInnis, Melvin G; Bostwick, Jolene R

    2015-04-01

    Treatment-resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of

  6. SSRI antidepressants: altered psychomotor development following exposure in utero?

    Science.gov (United States)

    2013-02-01

    Selective serotonin reuptake inhibitor antidepressants (SSRIs) are sometimes prescribed to pregnant women. The potential consequences for the unborn child are gradually becoming clearer. In a case-control study of 298 children with autism and 1507 controls, 6.7% of mothers of autistic children had been prescribed an antidepressant during the year before delivery, compared to 3.3% of control mothers. The antidepressant was usually an SSRI. A dozen other small epidemiological studies of neurological development in children exposed to antidepressants in utero have provided mixed results. Two of these studies suggested a risk of psychomotor retardation. In practice, SSRI antidepressants should only be considered for pregnant women when non-drug measures fail and when symptoms are sufficiently serious to warrant drug therapy.

  7. Increased use of antidepressants and decreasing suicide rates

    DEFF Research Database (Denmark)

    Erlangsen, Annette; Canudas-Romo, V; Conwell, Y

    2008-01-01

    -based record linkage. PARTICIPANTS: All individuals aged 50 years and older living in Denmark between 1 January 1996 and 31 December 2000 (N = 2,100,808). MAIN OUTCOME MEASURES: Suicide rates are calculated according to current antidepressant treatment status (no treatment, tricyclic antidepressants (TCA...... 100,000, recipients of antidepressants contributed to the decline by 0.9 suicides. Women redeeming antidepressant prescriptions accounted for 0.4 suicides of the observed reduction of 3.3 per 100,000. The average suicide rates for men receiving TCA and SSRI were 153.3 and 169.0 per 100,000 person......-years, respectively. Among older women, both TCA and SSRI users had an average suicide rate of 68.8 per 100,000 over the period examined. CONCLUSIONS: Just a small proportion of older adults dying by suicide were found to be in treatment with antidepressants at the time of death. Individuals in active treatment...

  8. The use of antidepressants in bipolar disorder patients with depression.

    Science.gov (United States)

    Bowden, Charles L; Singh, Vivek

    2016-01-01

    The proportion of time that bipolar patients experience depressive symptoms and clinical states, with associated psychosocial impairment and elevated risk of suicide, is significantly greater than the time spent in manic/hypomanic forms of bipolar disorders. Yet, manic states and symptoms have been the focus and interest of most clinical research over the past quarter century. Not a single antidepressant approved for treatment of major depressive disorder, as monotherapy, has received regulatory approval for treatment of bipolar depression as monotherapy, despite their common use in bipolar depression. We reviewed randomized studies, particularly ones initially intended for registration purposes, and systematic treatment guidelines, in development of this guide to treatment decision and implementation of interventions for depression in bipolar disorders. The Expert Opinion section emphasizes strategies, not individual agents. The efficacious performance of mood stabilizers and second-generation antipsychotics as a component of the strategy is strongly supported by published studies. However, this section relies largely on secondary publications and our combined clinical experience, as few randomized, blinded studies have had, as their focus, the comparison of combined regimens for depression. This article summarizes the design features and results of studies dealing with depressive features and intervention strategies for bipolar disorders. The emphasis of the recommendations is on pragmatic treatment decisions that clinicians can make to enhance the probability of both short and long term benefits for patients.

  9. Reevaluating the role of antidepressants in cancer-related depression: a systematic review and meta-analysis.

    Science.gov (United States)

    Riblet, Natalie; Larson, Robin; Watts, Bradley V; Holtzheimer, Paul

    2014-01-01

    Prior reviews evaluating the role of antidepressants in cancer-related depression have drawn conflicting conclusions. These reviews have also not explored differences in efficacy and tolerability between antidepressants. We conducted a meta-analysis to address these limitations. We searched Medline (1948-2013), the Cochrane Library (1800-2013), the Cumulative Index to Nursing and Allied Health Literature (1986-2013), ClinicalTrials.gov (2013) and meeting abstracts. We included randomized trials comparing antidepressants to placebo or no treatment for cancer-related depression. We used random effects to calculate standardized mean differences (SMD). Of 5178 potentially eligible citations, 9 trials (1169 subjects) met inclusion criteria. Trials of mianserin found a robust reduction in depression scores at ≥4 weeks of treatment (SMD: 0.60, 95% confidence interval (CI): 0.24-0.95). Similar, but less robust, results were observed with paroxetine (SMD: 0.22, 95% CI: 0.01-0.42) and fluoxetine (SMD 0.34, 95% CI: 0.02-0.66). Conversely, there was no advantage with amitriptyline or desipramine. Compared to placebo, the odds of dropping out due to side effect were higher with fluoxetine and paroxetine and lower with mianserin. Methodological quality was moderate. Paroxetine, fluoxetine and mianserin improve cancer-related depression but may vary in efficacy and tolerability. High-quality, randomized trials of newer antidepressant agents are needed to identify optimal treatments for managing cancer-related depression. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Quantum chemical analysis of potential anti-Parkinson agents

    Indian Academy of Sciences (India)

    Monoamine oxidases (MAOs) are amine oxidoreductase falvoenzymes that belong to the integral proteins of the outer mitochondrial membrane. MAO exists in two distinct isoforms; MAO-A and MAO-B. Inhibition of MAO-A and MAO-B is important for developing antidepressant and antiparkinson agents, respectively.

  11. Epigenetic Mechanisms of Depression and Antidepressants Action

    Science.gov (United States)

    Vialou, Vincent; Feng, Jian; Robison, Alfred J.; Nestler, Eric J.

    2013-01-01

    Epigenetic mechanisms, which control chromatin structure and function, mediate changes in gene expression that occur in response to diverse stimuli. Recent research has established that environmental events and behavioral experience induce epigenetic changes at particular gene loci that help shape neuronal plasticity and function, and hence behavior, and that some of these changes can be very stable and even persist for a lifetime. Increasing evidence supports the hypothesis that aberrations in chromatin remodeling and subsequent effects on gene expression within limbic brain regions contribute to the pathogenesis of depression and other stress-related disorders such as post-traumatic stress disorder and other anxiety syndromes. Likewise, the gradually developing but persistent therapeutic effects of antidepressant medications may be achieved in part via epigenetic mechanisms. This review discusses recent advances in understanding epigenetic regulation of stress-related disorders and focuses on three distinct aspects of stress-induced epigenetic pathology: the effects of stress and antidepressant treatment during adulthood, the life-long effects of early life stress on subsequent stress vulnerability, and the possible trans-generational transmission of stress-induced abnormalities. PMID:23020296

  12. Antidepressant therapy with milnacipran and venlafaxine

    Directory of Open Access Journals (Sweden)

    Lucilla Mansuy

    2010-08-01

    Full Text Available Lucilla MansuyPierre Fabre Médicament, Toulouse, FranceAbstract: Specific serotonin norepinephrine reuptake inhibitors (SNRIs have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs. Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.Keywords: milnacipran, venlafaxine, antidepressant efficacy, tolerability, dose-titration

  13. Role of corticosteroids in the antidepressant response

    Directory of Open Access Journals (Sweden)

    Pierscionek T

    2014-11-01

    Full Text Available Tomasz Pierscionek, Oluyemi Adekunte, Stuart Watson, I Nicol Ferrier, Akintunde Alabi Wolfson Research Institute, Institute of Neuroscience, Newcastle University, Campus for Ageing and Health, Newcastle upon Tyne, UK Abstract: Anything that engenders a homeostatic response in the tightly regulated hypothalamic–pituitary–adrenal (HPA axis may be thought of as a stressor and may exert an allostatic load, engendering a sustained change in the regulation of this system. Genetic, epigenetic, endocrine, post mortem, and animal studies suggest that dysregulation of the HPA axis plays a part in the pathophysiology of mood disorders and negatively impacts the antidepressant response and prognosis. Neuropsychological impairment, which is a common and disabling concomitant of depression, has been linked to disturbance of the HPA axis. A number of HPA axis-mediated treatment strategies have shown benefit in open or small-scale preliminary trials, and there are ongoing studies seeking both to replicate these initial findings and to develop new targets. HPA axis-based treatments are a fertile area of research, and much current thought pertains to the optimum targets, optimum population (including the potential for stratified medicine, and optimum outcome measures. We have, for instance, argued here that neuropsychological performance may be more sensitive and robust than scores on traditional depression rating scales. Keywords: hypothalamic–pituitary–adrenal axis, cortisol, corticotrophin-releasing hormone, arginine vasopressin, depression, bipolar disorder, antidepressant response

  14. Antidepressant Prescribing by Pediatricians: A Mixed-Methods Analysis.

    Science.gov (United States)

    Tulisiak, Anne K; Klein, Jillian A; Harris, Emily; Luft, Marissa J; Schroeder, Heidi K; Mossman, Sarah A; Varney, Sara T; Keeshin, Brooks R; Cotton, Sian; Strawn, Jeffrey R

    2017-01-01

    Among pediatricians, perceived knowledge of efficacy, tolerability, dosing, and side effects of antidepressants represent significant sources of variability in the use of these medications in youth with depressive and anxiety disorders. Importantly, the qualitative factors that relate to varying levels of comfort with antidepressants and willingness to prescribe are poorly understood. Using a mixed-methods approach, in-depth interviews were conducted with community-based and academic medical center-based pediatricians (N = 14). Interviews were audio recorded and iteratively coded; themes were then generated using inductive thematic analysis. The relationship between demographic factors, knowledge of antidepressants, dosing, and side effects, as well as prescribing likelihood scores for depressive disorders, anxiety disorders or co-morbid anxiety and depressive disorders, were evaluated using mixed models. Pediatricians reported antidepressants to be effective and well-tolerated. However, the likelihood of individual physicians initiating an antidepressant was significantly lower for anxiety disorders relative to depressive disorders with similar functional impairment. Pediatricians considered symptom severity/functional impairment, age and the availability of psychotherapy as they considered prescribing antidepressants to individual patients. Antidepressant choice was related to the physician׳s perceived knowledge and comfort with a particular antidepressant, financial factors, and the disorder-specific evidence base for that particular medication and consultation with mental health practitioners. Pediatricians noted similar efficacy and tolerability profiles for antidepressants in youth with depressive disorders and anxiety disorders, but tended to utilize "therapy first" approaches for anxiety disorders relative to depressive disorders. Parental and family factors that influenced prescribing of antidepressants by pediatricians included parental ambivalence

  15. Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

    Directory of Open Access Journals (Sweden)

    Gomez R.

    2001-01-01

    Full Text Available Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg, moclobemide (30 mg/kg, clonazepam (0.25 mg/kg, fluoxetine (20 mg/kg sertraline (30 mg/kg or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

  16. Optimal antidepressant dosing. Practical framework for selection, titration, and duration of therapy.

    Science.gov (United States)

    Nielsen, J W; Witek, M W; Hurwitz, S

    2000-10-01

    Appropriate antidepressant dosing and trial duration are crucial for successful treatment of depression. Before prescribing an antidepressant, primary care physicians should take into account each patient's history, responses to previous antidepressants, depressive symptoms, coexisting illnesses, and current prescriptions. Physicians must be able to help patients manage side effects and know when to discontinue treatment, switch antidepressants, or refer patients to a psychiatrist.

  17. NMDAR inhibition-independent antidepressant actions of ketamine metabolites

    Science.gov (United States)

    Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

    2016-01-01

    Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

  18. Antidepressants in Inflammatory Bowel Disease: A Systematic Review.

    Science.gov (United States)

    Macer, Benjamin J D; Prady, Stephanie L; Mikocka-Walus, Antonina

    2017-04-01

    Antidepressants are commonly used to treat symptoms of anxiety and depression in inflammatory bowel disease (IBD). Recent studies suggest a link between IBD activity and an individual's emotional state which raises the possibility that antidepressants may potentially modify the disease course of IBD. This systematic review thus primarily aims to evaluate the efficacy of antidepressants on IBD activity, and secondarily, on anxiety and depression. MEDLINE, EMBASE, Cochrane (IBD Group), CINAHL, AMED, PsycINFO, and OpenGrey were searched from 1990 onward with no restrictions on study design. A quality appraisal was conducted using several scales as appropriate for each study design. A narrative synthesis was also conducted. Fifteen eligible studies included in the review (1 randomized controlled trial, 2 cohorts, 1 case-control, 1 cross-sectional survey, 1 qualitative, 2 audits, 1 case series, and 6 case reports) examined a range of antidepressants. Twelve studies suggested that antidepressants have a positive impact on IBD course. Nine studies reported anxiety and depression as an outcome, of these 8 reported beneficial effects of antidepressants. Most of the studies were deemed to be at low risk of bias, apart from the case reports, which were at high risk of bias. This research indicates that antidepressants may have a beneficial effect on IBD course. However, it is currently not possible to determine their efficacy for certain because of the lack of randomized trials. Further trials using objective measures of IBD activity, longer follow-up periods, and larger sample sizes are needed.

  19. Effectiveness of a smartphone app for guiding antidepressant drug selection.

    Science.gov (United States)

    Man, Colin; Nguyen, Cathina; Lin, Steven

    2014-09-01

    Major depression is a prevalent chronic disease in the United States. However, many physicians lack access to decision support tools at point of care to help choose antidepressants in a rational, evidence-based manner. A patient-centered treatment model that uses a symptom-based approach to selecting antidepressants was developed into a smartphone application to provide instant, evidence-based recommendations and drug monographs. The purpose of this study was to assess the impact of this mobile application on the confidence level of family physicians in treating depression. The smartphone application was provided to 14 family medicine residents and attending physicians from the O'Connor Family Medicine Residency Program in San Jose, CA. Participants were asked to use the software as drug reference and clinical decision support during patient care activities. Three surveys were administered over a 12-week period to assess provider characteristics, outcome measures (ie, confidence in managing depression and choosing an initial antidepressant based on patient symptoms, medical comorbidities, potential side effects, and drug interactions), and fund of antidepressant knowledge. The average confidence levels in managing depression, starting an antidepressant on a patient with depression, and choosing an initial antidepressant based on patient symptoms increased significantly within the period of smartphone application usage. The average scores on the antidepressant knowledge tests also improved. The smartphone application was an effective tool for both increasing confidence in depression treatment and educating physicians. Future studies to evaluate the effectiveness and impact of smartphone applications on medical education and postgraduate training are warranted.

  20. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia.

    Science.gov (United States)

    Terevnikov, Viacheslav; Joffe, Grigori; Stenberg, Jan-Henry

    2015-05-19

    Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors' efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups--plausibly due to differences in the mechanisms of action. Antidepressants may not worsen the course of psychosis. Better designed

  1. Differences in Associations of Antidepressants and Hospitalization Due to Hyponatremia.

    Science.gov (United States)

    Farmand, Shermineh; Lindh, Jonatan D; Calissendorff, Jan; Skov, Jakob; Falhammar, Henrik; Nathanson, David; Mannheimer, Buster

    2018-01-01

    Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are important as a cause of hyponatremia. However, most studies have focused on the effect on sodium levels regardless of clinical symptoms, or have been too small to be able to discriminate between the effects of specific antidepressant drugs. The objective of the present study was to investigate the association between different groups of antidepressants and the risk of hospitalization due to hyponatremia. In this register-based case-control study of patients in the general Swedish population, we identified 14,359 individuals with a main diagnosis of hyponatremia. For every case, 4 matched controls were included (n = 57,382). To investigate the temporal aspects of drug-induced hyponatremia, antidepressant exposure was divided into patients with newly initiated and ongoing treatment. Univariable and multivariable logistic regression was used to analyze the association of antidepressant use and hospitalization. For newly initiated antidepressants, adjusted odds ratios (95% confidence interval) for a main diagnosis of hyponatremia compared with controls were: citalopram 5.50 (4.71-6.44); sertraline 4.96 (3.81-6.48); venlafaxine 5.28 (3.20-8.83); tricyclic antidepressants 1.59 (1.13-2.24); and mirtazapine 2.54 (2.04-3.16). Adjusted odds ratio (confidence interval) for individuals with ongoing treatment ranged from 0.57 (0.52-0.63) for citalopram to 1.08 (0.85-1.36) for other SSRIs. There was a strong association between newly initiated treatment with SSRIs or venlafaxine and hospitalization due to hyponatremia. The association for tricyclic antidepressants and mirtazapine was small to moderate. In contrast, there was no evidence that ongoing treatment with antidepressants increases the risk for hospitalization due to hyponatremia. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  2. Gender display in Scandinavian and American advertising for antidepressants.

    Science.gov (United States)

    Lövdahl, U; Riska, A; Riska, E

    1999-12-01

    This study examines whether depiction of users of antidepressants in advertisements for antidepressants in the 1995 issues of the major medical journal in each of Denmark, Finland, Norway, and Sweden differs from that in the American Journal of Psychiatry. The results show that the people shown in the Danish, Finnish, and Norwegian journals are predominantly women, whereas depiction of users in the American and Swedish advertising is predominantly of couples. The portrayals in the 1995 advertising are of antidepressants as female gendered; a feature that was not seen in advertising for psychotropic drugs in the Nordic countries in the 1980s.

  3. Extracorporeal treatment for tricyclic antidepressant poisoning

    DEFF Research Database (Denmark)

    Yates, Christopher; Galvao, Tais; Sowinski, Kevin M

    2014-01-01

    methodology, the subgroup responsible for this poison reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND......The Extracorporeal Treatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, the workgroup presents its results for tricyclic antidepressants (TCAs). After an extensive literature search, using a predefined...... yielding a very low quality of evidence for all recommendations. Data on 108 patients, including 12 fatalities, were abstracted. The workgroup concluded that TCAs are not dialyzable and made the following recommendation: ECTR is not recommended in severe TCA poisoning (1D). The workgroup considers...

  4. Antidepressants and advertising: psychopharmaceuticals in crisis.

    Science.gov (United States)

    Greenslit, Nathan P; Kaptchuk, Ted J

    2012-03-01

    As the efficacy and science of psychopharmaceuticals has become increasingly uncertain, marketing of these drugs to both physicians and consumers continues to a central part of a multi-billion dollar per year industry in the United States. We explore how such drug marketing portrays idealized scientific relationships between psychopharmaceuticals and depression; how multiple stakeholders, including scientists, regulatory agencies, and patient advocacy groups, negotiate neurobiological explanations of mental illness; and how the placebo effect has become a critical issue in these debates, including the possible role of drug advertising to influence the placebo effect directly. We argue that if and how antidepressants "work" is not a straightforward objective question, but rather a larger social contest involving scientific debate, the political history of the pharmaceutical industry, cultural discourses surrounding the role of drugs in society, and the interpretive flexibility of personal experience.

  5. Antidepressants & suicide: putting the risk in perspective.

    Science.gov (United States)

    Howland, Robert H

    2007-07-01

    Suicidal thoughts are a symptom of depression, and completed suicide is a tragic complication of depressive illness. Although pharmacotherapy is effective for the treatment of depression, the U.S. Food and Drug Administration has ordered that all antidepressant medications carry a warning indicating that they are associated with an increased risk of suicidal thinking, feeling, and behavior in children, adolescents, and young adults. These warnings have received much attention in the general media and have caused much controversy and debate about the relative safety of these commonly used drugs and the appropriateness of their use, especially in younger patients. In this article, I will discuss this issue with the goal of putting the risk in perspective.

  6. Emerging antidepressants to treat major depressive disorder.

    Science.gov (United States)

    Block, Samantha G; Nemeroff, Charles B

    2014-12-01

    Depression is a common disorder with an annual risk of a depressive episode in the United States of 6.6%. Only 30-40% of patients remit with antidepressant monotherapy, leaving 60-70% of patients who do not optimally respond to therapy. Unremitted depressive patients are at increased risk for suicide. Considering the prevalence of treatment resistant depression and its consequences, treatment optimization is imperative. This review summarizes the latest treatment modalities for major depressive disorder including pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation and psychotherapy. Through advancements in research to better understand the pathophysiology of depression, advances in treatment will be realized. Copyright © 2014. Published by Elsevier B.V.

  7. Adherence to anti-depressant medication

    DEFF Research Database (Denmark)

    Buus, Niels

    2014-01-01

    The study of medicine taking is controversial as it often reveals a discrepancy between healthcare professionals' advice and patients' actual behaviour. Qualitative researchers have examined depressed people's adherence to prescriptions of antidepressants by exploring the meaning they impute...... semi-structured interviews with 16 people four times during the year following an admission to hospital for depression. Data were collected in 2008-2009 in the Region of Southern Denmark. The study was based on an interactionist conception of social career and data were analysed thematically. Findings...... indicated that participants were confronted with recurrent challenges related to being depressed and taking medicine, and they learned how to manage these challenges in a post-admission career with two distinct stages: the basic restitution stage and the frustrated search stage. Medicine-taking depended...

  8. Antidepressants and Advertising: Psychopharmaceuticals in Crisis

    Science.gov (United States)

    Greenslit, Nathan P.; Kaptchuk, Ted J.

    2012-01-01

    As the efficacy and science of psychopharmaceuticals has become increasingly uncertain, marketing of these drugs to both physicians and consumers continues to a central part of a multi-billion dollar per year industry in the United States. We explore how such drug marketing portrays idealized scientific relationships between psychopharmaceuticals and depression; how multiple stakeholders, including scientists, regulatory agencies, and patient advocacy groups, negotiate neurobiological explanations of mental illness; and how the placebo effect has become a critical issue in these debates, including the possible role of drug advertising to influence the placebo effect directly. We argue that if and how antidepressants “work” is not a straightforward objective question, but rather a larger social contest involving scientific debate, the political history of the pharmaceutical industry, cultural discourses surrounding the role of drugs in society, and the interpretive flexibility of personal experience. PMID:22461754

  9. New Hippocampal Neurons Mature Rapidly in Response to Ketamine But Are Not Required for Its Acute Antidepressant Effects on Neophagia in Rats123

    Science.gov (United States)

    Soumier, Amelie; Carter, Rayna M.; Schoenfeld, Timothy J.

    2016-01-01

    Abstract Virtually all antidepressant agents increase the birth of granule neurons in the adult dentate gyrus in rodents, providing a key basis for the neurogenesis hypothesis of antidepressant action. The novel antidepressant ketamine, however, shows antidepressant activity in humans within hours, far too rapid for a mechanism involving neuronal birth. Ketamine could potentially act more rapidly by enhancing maturation of new neurons born weeks earlier. To test this possibility, we assessed the effects of S-ketamine (S-(+)-ketamine hydrochloride) injection on maturation, as well as birth and survival, of new dentate gyrus granule neurons in rats, using the immediate-early gene zif268, proliferating cell nuclear antigen, and BrdU, respectively. We show that S-ketamine has rapid effects on new neurons, increasing the proportion of functionally mature young granule neurons within 2 h. A single injection of S-ketamine also increased cell proliferation and functional maturation, and decreased depressive-like behavior, for at least 4 weeks in rats treated with long-term corticosterone administration (a depression model) and controls. However, the behavioral effects of S-ketamine on neophagia were unaffected by elimination of adult neurogenesis. Together, these results indicate that ketamine has surprisingly rapid and long-lasting effects on the recruitment of young neurons into hippocampal networks, but that ketamine has antidepressant-like effects that are independent of adult neurogenesis. PMID:27066531

  10. Factors influencing the choice of antidepressants: A study of antidepressant prescribing practice at University psychiatric clinic in Belgrade

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2012-01-01

    Full Text Available Background/Aim. Antidepressants are a widely used class of drugs. The aim of this study was to investigate different aspects of antidepressant prescribing practice at University Psychiatric Clinic in Belgrade. Methods. This cross-sectional study was carried out by retrospective analysis of the patient's medical charts. The study included all patients with antidepressant prescribed at discharge during 2009 (n = 296. The evaluation was focused on patient- related factors (socio-demographic and illness related, psychiatrist-related factors (sex and duration of working experience and drug related factors (type of antidepressant, dose, polypharmacy and reimbursement by national health insurance. Results. Antidepressants were prescribed for unipolar depression (F32-34, ICD X either without comorbidity (46.2% or with comorbidity (24.7%, mostly as a monotherapy (91% had one antidepressant, to the patients who were 65% female, aged 50.1 ± 8.9, most of them with 12 years of education (52.6%, married (69.3% and employed (55.9%. The majority of patients had a history of two hospitalizations (Med 2; 25th-75th perc. 1-4 during nine years (Med 9; 25th-75th perc. 2-15 after the first episode of depression. Among them, 19% were found to be suicidal in a lifetime. The single most prescribed antidepressant was sertraline (20.4%, followed by fluoxetine (13.3% and maprotiline (11.7%. Utilization of antidepressants was positively correlated with the rate of reimbursement (p < 0.01. The most prescribed antidepressant group was selective serotonin reuptake inhibitors (SSRI (47.8%, followed by tricyclic antidepresants (TCA (25.3% and new antidepressants - venlafaxine, tianeptine, mirtazapine, bupropion, trazodone (15.1%. Most of the drugs were prescribed in doses which are at the lower end of the recommended dose-range. Regarding severity of the actual depressive episode, TCA were prescribed for severe depression with psychotic features, while SSRI were choice for

  11. Effect of anti-depressants on neuro-behavioural consequences following impact accelerated traumatic brain injury in rats.

    Science.gov (United States)

    Mahesh, Radhakrishnan; Pandey, Dilip Kumar; Katiyar, Shruti; Kukade, Gaurav; Viyogi, Shruti; Rudra, Anjuman

    2010-05-01

    Disruption of normal neuronal networks and neurotransmitters like serotonin and norepinephrine levels in post traumatic brain injury (TBI) are observed to be the primary causative agent for depression/anxiety. This communication reports the efficacy of various classes' anti-depressants in the treatment of depression/anxiety following TBI in rats. Chronic treatment with anti-depressants (escitalopram and venlafaxine) leads to improvement in the depressive/anxiogenic-like behaviour in the TBI rat and corroborates the notion of the involvement of serotonin and norepinephrine in the behavioural consequences of post-TBI. Chronic treatments with escitalopram and venlafaxine significantly reversed the effect of TBI as compared to vehicle-treated TBI group. The results showed a quantitative battery of neuro-behavioural functional assessments that correlates with neuronal damage following traumatic brain injury.

  12. Antidepressant sales and regional variations of suicide mortality in Germany

    NARCIS (Netherlands)

    Blüml, V; Helbich, M.; Mayr, M; Turnwald, R; Vyssoki, B; Lewitzka, U; Hartung, S; Plener, P; Fegert, J; Kapusta, N

    2017-01-01

    Suicides account for over one million deaths per year worldwide with depression among the most important risk factors. Epidemiological research into the relationship between antidepressant utilization and suicide mortality has shown heterogeneous and contradictory results. Different methodological

  13. Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

    Science.gov (United States)

    Yun, Sanghee; Reynolds, Ryan P; Petrof, Iraklis; White, Alicia; Rivera, Phillip D; Segev, Amir; Gibson, Adam D; Suarez, Maiko; DeSalle, Matthew J; Ito, Naoki; Mukherjee, Shibani; Richardson, Devon R; Kang, Catherine E; Ahrens-Nicklas, Rebecca C; Soler, Ivan; Chetkovich, Dane M; Kourrich, Saïd; Coulter, Douglas A; Eisch, Amelia J

    2018-04-16

    Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

  14. Antidepressant-like potentials of Buchholzia Coriacea seed extract ...

    African Journals Online (AJOL)

    active metabolites, and the folklore documented its use in neuro-behavioral despairs. Previous study in our laboratory shows that methanol extracts of Buchholzia coriacea (MEBC) seeds possess antidepressant-like potentials in laboratory rodents.

  15. Effects of antidepressant drugs on different receptors in the brain

    International Nuclear Information System (INIS)

    Hall, H.; Oegren, S.-O.

    1981-01-01

    Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands ([ 3 H]WB4101, [ 3 H]QNB, [ 3 H]d-LSD, [ 3 H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [ 3 H]mepyramine, [ 3 H]d-LSD and [ 3 H]WB4101 while it was very weak on [ 3 H]QNB-binding. Nomifensine and the specific 5-HT uptake inhibitors zimelidine and alaproclate had very low affinity for these receptors. All the antidepressants tested were practically devoid of activity on [ 3 H]DHA binding, [ 3 H]spiroperidol binding, [ 3 H]flunitrazepam binding, [ 3 H]muscimol binding and [ 3 H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed. (Auth.)

  16. Increased use of antidepressants at the end of life

    DEFF Research Database (Denmark)

    Hansen, Dorte Gilså; Rosholm, Jens-Ulrik; Gichangi, Anthony

    2007-01-01

    BACKGROUND: The new antidepressants are generally effective and safe for older people, but may have serious side-effects. The use has been rapidly increasing, but focus on upper age groups has been limited. The pattern of antidepressant use as death approaches has never been analysed. OBJECTIVE......: To analyse the use of antidepressants among individuals aged 65 years and above with respect to time trends, age and proximity to death. DESIGN: Population-based prescription study. SETTING: The County of Funen, Denmark, 1992-2004 (approximately 470,000 inhabitants). RESULTS: The 1-year prevalence...... of antidepressants increases steadily over time in all age groups. Among the 65+ year-olds it also increases with age and differs substantially between the youngest and the oldest. Very high prevalences are observed: 26.8% among females 85-89 years old and 17.5% among males 85 years and above in 2004. In all age...

  17. Increase in depression diagnoses and prescribed antidepressants among young girls

    DEFF Research Database (Denmark)

    Skovlund, Charlotte Wessel; Kessing, Lars Vedel; Mørch, Lina Steinrud

    2017-01-01

    AIMS: To analyse trends in depression diagnoses and antidepressant use according to age and gender. METHODS: Nationwide cohort study including all women and men of 10-49 years living in Denmark during 2000-2013. The Psychiatric Registry and Prescription Registry provided data on depression...... diagnoses and antidepressant medication, respectively. Incidence rates as well as 1-year prevalence rates were calculated. RESULTS: The incidence and 1-year prevalence rates of depression diagnoses increased during 2000-2013. The women/men rates were 2.0 for both 1-year prevalence of depressions diagnoses...... and antidepressant use. For adolescent girls, the absolute increase was 3 per 1000 for depression diagnoses and 8 per 1000 for first use of antidepressants, compared to boys who had an increase of 1.1 and 3 per 1000, respectively. Before puberty, boys and girls had almost the same incidence rates of both depression...

  18. Acute antidepressant drug administration and autobiographical memory recall

    DEFF Research Database (Denmark)

    Papadatou-Pastou, Marietta; Miskowiak, Kamilla W; Williams, J Mark G

    2012-01-01

    Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration of the antidepress...... of reboxetine on emotional memory extends to recall of personally experienced events. Such effects may be relevant to the cognitive improvements found with recovery from depression and with the mechanism of action of contemporary antidepressant drugs.......Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration...... in the processing of positive versus negative memories was reduced following reboxetine compared with placebo in the left frontal lobe (extending into the insula) and the right superior temporal gyrus. This was paired with increased memory speed in volunteers given reboxetine versus placebo. The effect...

  19. Antidepressants for cocaine dependence and problematic cocaine use.

    Science.gov (United States)

    Pani, Pier Paolo; Trogu, Emanuela; Vecchi, Simona; Amato, Laura

    2011-12-07

    Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication development. To investigate the efficacy and acceptability of antidepressants alone or in combination with any psychosocial intervention for the treatment of cocaine dependence and problematic cocaine use. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE and CINAHL in July 2011 and researchers for unpublished trials. Randomised clinical trials comparing antidepressants alone or associated with psychosocial intervention with placebo, no treatment, other pharmacological or psychosocial interventions. Two authors independently assessed trial quality and extracted data. 37 studies were included in the review (3551 participants).Antidepressants versus placebo: results for dropouts did not show evidence of difference, 31 studies, 2819 participants, RR 1.03 (Cl 95% 0.93 to 1.14). Looking at Abstinence from cocaine use, even though not statistically significant, the difference shown by the analysis in the three-weeks abstinence rate was in favour of antidepressants (eight studies, 942 participants, RR 1.22 (Cl 95% 0.99 to 1.51)). Considering only studies involving tricyclics, five studies, 367 participants, or only desipramine, four studies, 254 participants, the evidence was in favour of antidepressants. However, selecting only studies with operationally defined diagnostic criteria, statistical significance favouring antidepressants, as well as the trend for significance shown by the full sample, disappeared. Looking at safety issues, the results did not show evidence of differences (number of patients withdrawn for medical reasons, thirteen studies, 1396 participants, RR 1.39 (Cl 95% 0.91 to 2.12)). Subgroup analysis considering length of the trial, associated opioid dependence or associated psychosocial interventions as confounding factors, failed in showing consistent and

  20. Explanatory models of depression and treatment adherence to antidepressant medication

    DEFF Research Database (Denmark)

    Buus, Niels; Johannessen, Helle; Stage, Kurt Bjerregaard

    2012-01-01

    and medicine were not central. However, taking antidepressant medication was a meaningful part of being admitted to hospital, and the adoption of the rhetoric and practices of biomedicine strengthened patients' sense of control and hope for recovery. If medicine was ineffective, the explanatory models...... legitimised alternative strategies towards recovery, including non-adherence. CONCLUSIONS: The patients' reasons for adhering to antidepressants included a range of diverse psychosocial issues, and could be regarded as a central part of their common sense illness management....

  1. Use of antidepressants and risk of epithelial ovarian cancer.

    Science.gov (United States)

    Mørch, Lina S; Dehlendorff, Christian; Baandrup, Louise; Friis, Søren; Kjaer, Susanne K

    2017-12-01

    Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we identified all women (cases) aged 30-84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n = 4,103) and matched each case to 20 population controls (n = 58,706) by risk-set matching. Data on drug use (including tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other antidepressants were close to unity [tricyclic and related antidepressants: OR, 0.99 (95% CI, 0.78-1.26); other antidepressants: OR, 1.05 (95% CI, 0.76-1.46)]. For individual types of SSRI, reduced ORs were observed for citalopram OR, 0.78 (95% CI, 0.66-0.93), paroxetine 0.79 (95% CI, 0.56-1.12) and sertraline 0.80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive properties of these drugs. © 2017 UICC.

  2. Efficacy of New Generation Antidepressants: Differences Seem Illusory

    OpenAIRE

    Del Re A. C.; Spielmans Glen I.; Flueckiger Christoph; Wampold Bruce E.

    2013-01-01

    BACKGROUND: Recently, Cipriani and colleagues examined the relative efficacy of 12 new-generation antidepressants on major depression using network meta-analytic methods. They found that some of these medications outperformed others in patient response to treatment. However, several methodological criticisms have been raised about network meta-analysis and Cipriani's analysis in particular which creates the concern that the stated superiority of some antidepressants relative to others may be ...

  3. Antidepressant Treatment for Acute Bipolar Depression: An Update

    Directory of Open Access Journals (Sweden)

    Ben H. Amit

    2012-01-01

    Full Text Available While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD, recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability. Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review. Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy. Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted.

  4. Antidepressants versus placebo in major depression: an overview.

    Science.gov (United States)

    Khan, Arif; Brown, Walter A

    2015-10-01

    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. © 2015 World Psychiatric Association.

  5. Antidepressant medication use, depression, and the risk of preeclampsia.

    Science.gov (United States)

    Avalos, Lyndsay Ammon; Chen, Hong; Li, De-Kun

    2015-02-01

    To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. We conducted a retrospective, population-based cohort study that linked automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser Permanente Northern California members between 2010 and 2012. The overall risk of preeclampsia was 4.5%. The timing of antidepressant medication exposure was an important factor. A significant increase in the risk of preeclampsia emerged for women with a depression diagnosis who took antidepressant medications during the second trimester compared to women with untreated depression (adjusted relative risk [aRR]: 1.6, 95% CI: 1.06, 2.39) and to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations existed for women who took antidepressant medications, but without depression. In contrast, depressed women with psychotherapy showed no increased risk of preeclampsia compared to women with untreated depression or no depression. There was also a statistically significant relationship between the duration of antidepressant medication use and preeclampsia. The observed association appeared stronger for selective serotonin reuptake inhibitor (SSRI) use, although a nonsignificant trend was also noted for use of norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Study findings suggest that antidepressant use during pregnancy may increase the risk of preeclampsia, especially use during the second trimester.

  6. Anti-inflammatory agents in the treatment of bipolar depression

    DEFF Research Database (Denmark)

    Rosenblat, Joshua D; Kakar, Ron; Berk, Michael

    2016-01-01

    the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, Psych......INFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified...... for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size...

  7. Anti-convulsants and anti-depressants.

    Science.gov (United States)

    Dickenson, A H; Ghandehari, J

    2007-01-01

    systems that use the monoamines. These pathways become more active after nerve injury and are the site of action of anti-depressants. This chapter reviews the evidence and mechanisms of drugs, both anti-depressants and anti-convulsants, that are believed to be effective in pain control, with a major emphasis on the neuropathic state.

  8. Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain.

    Science.gov (United States)

    Tikhonova, Maria; Kulikov, Alexander V

    2012-08-31

    Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: [1] BDNF is effective in the treatment of some genetically defined behavioral disturbances; [2] BDNF influences sexually-motivated behavior; [3] Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; [4] ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on

  9. Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis.

    Science.gov (United States)

    Strawn, Jeffrey R; Welge, Jeffrey A; Wehry, Anna M; Keeshin, Brooks; Rynn, Moira A

    2015-03-01

    Randomized controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety, or tolerability of these medications in pediatric anxiety disorders. A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-obsessive compulsive disorder (OCD) anxiety disorders was undertaken using a search of PubMed/Medline (1966-2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality, and adverse events. Additionally, pharmacologic variables were explored with regard to effect size, although no correction for multiple comparisons was made with regard to these relationships. Nine trials involving 1,673 patients and six medications were included. All SSRI/SSNRIs evaluated demonstrated efficacy, and the meta-analytic estimate of effect was of moderate magnitude (Cohen's d = 0.62, confidence interval [CI]: 0.34-0.89, P = .009) and there was evidence of modest heterogeneity (I(2) = 0.29, P = .103). Activation trended toward being more likely with antidepressant treatment (OR: 1.86, CI: 0.98-3.53, P = .054), but no increased risk was observed for nausea/abdominal symptoms (P = .262), discontinuation as a result of an adverse event (P = .132), or suicidality (OR: 1.3, CI: 0.53-3.2, P = .514). Finally, the effect size correlated with the serotonergic specificity of the agent (R = .79, P = .021). Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size. © 2014 Wiley Periodicals, Inc.

  10. Monoaminergic Antidepressants in the Relief of Pain: Potential Therapeutic Utility of Triple Reuptake Inhibitors (TRIs

    Directory of Open Access Journals (Sweden)

    Bruno P. Guiard

    2011-01-01

    Full Text Available Over 75% of depressed patients suffer from painful symptoms predicting a greater severity and a less favorable outcome of depression. Imaging, anatomical and functional studies have demonstrated the existence of common brain structures, neuronal pathways and neurotransmitters in depression and pain. In particular, the ascending serotonergic and noradrenergic pathways originating from the raphe nuclei and the locus coeruleus; respectively, send projections to the limbic system. Such pathways control many of the psychological functions that are disturbed in depression and in the perception of pain. On the other hand, the descending pathways, from monoaminergic nuclei to the spinal cord, are specifically implicated in the inhibition of nociception providing rationale for the use of serotonin (5-HT and/or norepinephrine (NE reuptake inhibitors (SSRIs, NRIs, SNRIs, in the relief of pain. Compelling evidence suggests that dopamine (DA is also involved in the pathophysiology and treatment of depression. Indeed, recent insights have demonstrated a central role for DA in analgesia through an action at both the spinal and suprasinal levels including brain regions such as the periaqueductal grey (PAG, the thalamus, the basal ganglia and the limbic system. In this context, dopaminergic antidepressants (i.e., containing dopaminergic activity, such as bupropion, nomifensine and more recently triple reuptake inhibitors (TRIs, might represent new promising therapeutic tools in the treatment of painful symptoms with depression. Nevertheless, whether the addition of the dopaminergic component produces more robust effects than single- or dual-acting agents, has yet to be demonstrated. This article reviews the main pathways regulating pain transmission in relation with the monoaminergic systems. It then focuses on the current knowledge regarding the in vivo pharmacological properties and mechanism of action of monoaminergic antidepressants including SSRIs, NRIs

  11. Impact of lithium alone and in combination with antidepressants on cytokine production in vitro.

    Science.gov (United States)

    Petersein, Charlotte; Sack, Ulrich; Mergl, Roland; Schönherr, Jeremias; Schmidt, Frank M; Lichtblau, Nicole; Kirkby, Kenneth C; Bauer, Katrin; Himmerich, Hubertus

    2015-01-01

    Lithium is an important psychopharmacological agent for the treatment of unipolar as well as bipolar affective disorders. Lithium has a number of side effects such as hypothyroidism and aggravation of psoriasis. On the other hand, lithium has pro-inflammatory effects, which appear beneficial in some disorders associated with immunological deficits, such as human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE). Therefore, immunological characteristics of lithium may be an important consideration in individualized therapeutic decisions. We measured the levels of the cytokines interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-22, IL-17 and tumour necrosis factor (TNF)-α in the stimulated blood of thirty healthy subjects supplemented with lithium alone, the antidepressants citalopram, escitalopram or mirtazapine alone, the combination of each antidepressant with lithium, and a no drug control. These drugs were tested under three blood stimulant conditions: murine anti-human CD3 monoclonal antibody OKT3 and the 5C3 monoclonal antibody (OKT3/5C3), phytohemagglutinin (PHA), and unstimulated blood. Lithium, alone and in combination with any of the tested antidepressants, led to a consistent increase of IL-1ß, IL-6 and TNF-α levels in the unstimulated as well as the stimulated blood. In the OKT3/5C3- and PHA-stimulated blood, IL-17 production was significantly enhanced by lithium. Lithium additionally increased IL-2 concentrations significantly in PHA-stimulated blood. The data support the view that lithium has pro-inflammatory properties. These immunological characteristics may contribute to side effects of lithium, but may also explain its beneficial effects in patients suffering from HIV infection or SLE.

  12. Suicidality and aggression during antidepressant treatment

    DEFF Research Database (Denmark)

    Sharma, Tarang; Guski, Louise Schow; Freund, Nanna

    2016-01-01

    OBJECTIVE: To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. MAIN OUTCOME MEASURES: Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. DATA SOURCES: Clinical...... for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.......93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary...

  13. Suicidality and aggression during antidepressant treatment

    DEFF Research Database (Denmark)

    Sharma, Tarang; Guski, Louise Schow; Freund, Nanna

    2016-01-01

    Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis.Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.Data sources Clinical study...... of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.......95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli...

  14. A new strategy for antidepressant prescription

    Directory of Open Access Journals (Sweden)

    Francis Lavergne

    2010-11-01

    Full Text Available From our research and literature search we propose an understanding of the mechanism of action of antidepressants (ADs that should lead to increase efficacy and tolerance.We understand that ADs promote synaptic plasticity and neurogenesis. This promotion is linked with dopamine (DA stimulation. Literature shows that all ADs (chemical, electroconvulsive therapy, repetitive transcranial magnetic stimulation, sleep deprivation increase at least one neuromodulator (serotonin, noradrenaline or DA; this article focuses on DA release or turn-over in the frontal cortex. DA increase promotes synaptic plasticity with an inverted U shape dose-response curve. Specific interaction between DA and glutamate relies on DA (D1 receptors and Glutamate (NMDA receptors and/or on neurotrophic factors activation. With the understanding that all ADs have a common, final, DArgic stimulation that promotes synaptic plasticity we can predict that:1AD efficiency is related to the compound strength for inducing DArgic stimulation.2AD efficiency presents a therapeutic window that coincides with the inverted U shape DA response curve.3AD delay of action is related to a synaptogenesis and neurogenesis delay of action.4The minimum efficient dose can be found by starting at a low dosage and increasing up to the patient response. 5An increased tolerance requires a concomitant prescription of a few ADs, with different or opposite adverse effects, at a very low dose.6ADs could improve all diseases with cognitive impairments and synaptic depression by increasing synaptic plasticity and neurogenesis.

  15. Efficacy of new generation antidepressants: differences seem illusory.

    Directory of Open Access Journals (Sweden)

    A C Del Re

    Full Text Available BACKGROUND: Recently, Cipriani and colleagues examined the relative efficacy of 12 new-generation antidepressants on major depression using network meta-analytic methods. They found that some of these medications outperformed others in patient response to treatment. However, several methodological criticisms have been raised about network meta-analysis and Cipriani's analysis in particular which creates the concern that the stated superiority of some antidepressants relative to others may be unwarranted. MATERIALS AND METHODS: A Monte Carlo simulation was conducted which involved replicating Cipriani's network meta-analysis under the null hypothesis (i.e., no true differences between antidepressants. The following simulation strategy was implemented: (1 1000 simulations were generated under the null hypothesis (i.e., under the assumption that there were no differences among the 12 antidepressants, (2 each of the 1000 simulations were network meta-analyzed, and (3 the total number of false positive results from the network meta-analyses were calculated. FINDINGS: Greater than 7 times out of 10, the network meta-analysis resulted in one or more comparisons that indicated the superiority of at least one antidepressant when no such true differences among them existed. INTERPRETATION: Based on our simulation study, the results indicated that under identical conditions to those of the 117 RCTs with 236 treatment arms contained in Cipriani et al.'s meta-analysis, one or more false claims about the relative efficacy of antidepressants will be made over 70% of the time. As others have shown as well, there is little evidence in these trials that any antidepressant is more effective than another. The tendency of network meta-analyses to generate false positive results should be considered when conducting multiple comparison analyses.

  16. Efficacy of new generation antidepressants: differences seem illusory.

    Science.gov (United States)

    Del Re, A C; Spielmans, Glen I; Flückiger, Christoph; Wampold, Bruce E

    2014-01-01

    Recently, Cipriani and colleagues examined the relative efficacy of 12 new-generation antidepressants on major depression using network meta-analytic methods. They found that some of these medications outperformed others in patient response to treatment. However, several methodological criticisms have been raised about network meta-analysis and Cipriani's analysis in particular which creates the concern that the stated superiority of some antidepressants relative to others may be unwarranted. A Monte Carlo simulation was conducted which involved replicating Cipriani's network meta-analysis under the null hypothesis (i.e., no true differences between antidepressants). The following simulation strategy was implemented: (1) 1000 simulations were generated under the null hypothesis (i.e., under the assumption that there were no differences among the 12 antidepressants), (2) each of the 1000 simulations were network meta-analyzed, and (3) the total number of false positive results from the network meta-analyses were calculated. Greater than 7 times out of 10, the network meta-analysis resulted in one or more comparisons that indicated the superiority of at least one antidepressant when no such true differences among them existed. Based on our simulation study, the results indicated that under identical conditions to those of the 117 RCTs with 236 treatment arms contained in Cipriani et al.'s meta-analysis, one or more false claims about the relative efficacy of antidepressants will be made over 70% of the time. As others have shown as well, there is little evidence in these trials that any antidepressant is more effective than another. The tendency of network meta-analyses to generate false positive results should be considered when conducting multiple comparison analyses.

  17. The role of NMDA receptor and nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effect of dextromethorphan in mice forced swimming test and tail suspension test.

    Science.gov (United States)

    Sakhaee, Ehsan; Ostadhadi, Sattar; Khan, Muhammad Imran; Yousefi, Farbod; Norouzi-Javidan, Abbas; Akbarian, Reyhaneh; Chamanara, Mohsen; Zolfaghari, Samira; Dehpour, Ahmad-Reza

    2017-01-01

    Depression is a devastating disorder which has a high impact on the wellbeing of overall society. As such, need for innovative therapeutic agents are always there. Most of the researchers focused on N-methyl-d-aspartate receptor to explore the antidepressant like activity of new therapeutic agents. Dextromethorphan is a cough suppressant agent with potential antidepressant activity reported in mouse force swimming test. Considering N-methyl-d-aspartate as a forefront in exploring antidepressant agents, here we focused to unpin the antidepressant mechanism of dextromethorphan targeting N-methyl-d-aspartate receptor induced nitric oxide-cyclic guanosine monophosphate signaling. Dextromethorphan administered at a dose of 10 and 30mg/kg i.p significantly reduced the immobility time. Interestingly, this effect of drug (30mg/kg) was inhibited when the animals were pretreated either with N-methyl-d-aspartate (75mg/kg), or l-arginine (750mg/kg) as a nitric oxide precursor and/or sildenafil (5mg/kg) as a phosphodiesterase 5 inhibitor. However, the antidepressant effect of Dextromethorphan subeffective dose (3mg/kg) was augmented when the animals were administered with either L-NG-Nitroarginine methyl ester (10mg/kg) non-specific nitric oxide synthase inhibitor, 7-Nitroindazole (30mg/kg) specific neural nitric oxide synthase inhibitor, MK-801 (0.05mg/kg) an N-methyl-d-aspartate receptor antagonist but not aminoguanidine (50mg/kg) which is specific inducible nitric oxide synthase inhibitor as compared to the drugs when administered alone. No remarkable effect on locomotor activity was observed during open field test when the drugs were administered at the above mentioned doses. Therefore, it is evident that the antidepressant like effect of Dextromethorphan is owed due to its inhibitory effect on N-methyl-d-aspartate receptor and NO- Cyclic guanosine monophosphate pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Techniques for studying inverse agonist activity of antidepressants at recombinant nonedited 5-HT(₂C-INI) receptor and native neuronal 5-HT(₂C) receptors.

    Science.gov (United States)

    Seimandi, Mathieu; Bockaert, Joël; Marin, Philippe

    2010-01-01

    Serotonin (5-HT)(₂C) receptors play a major role in the regulation of mood, and alteration of their functional status has been implicated in the etiology of affect disorders. Correspondingly, they represent an important target for various antidepressant categories, including tricyclics, tetracyclics, mCPP derivatives, specific serotonin reuptake inhibitors, and agomelatine, which exhibit medium to high affinities for 5-HT(₂C) receptors and behave as antagonists. Antidepressant effects of 5-HT(₂C) antagonists have been attributed to a disinhibition of mesocorticolimbic dopaminergic pathways, which exert a beneficial influence upon mood and cognitive functions altered in depression. However, recent experimental evidence revealed a prominent role of constitutive activity in the tonic inhibitory control of dopaminergic transmission exerted by 5-HT(₂C) receptors in specific brain areas such as the nucleus accumbens. Accordingly, alteration in the constitutive activity of 5-HT(₂C) receptors might participate in the induction of depressed states and drugs with inverse agonist properties should themselves be effective antidepressant agents and, possibly, more active than neutral antagonists. This highlights the relevance of systematically evaluating inverse agonist versus neutral antagonist activities of antidepressants acting at 5-HT(₂C) receptors. Here, we provide a detailed description of a palette of cellular assays exploiting constitutive activity of 5-HT(₂C) receptor expressed in heterologous cells (such as HEK-293 cells) toward Gq-operated signaling or their constitutive association with β-arrestins to evaluate inverse agonist activity of antidepressants. We also describe an approach allowing discrimination between inverse agonist and neutral antagonist activities of antidepressants at native constitutively active receptors expressed in cultured cortical neurons, based on previous findings indicating that prolonged treatments with inverse agonists

  19. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis.

    Science.gov (United States)

    Gobbi, G; Bambico, F R; Mangieri, R; Bortolato, M; Campolongo, P; Solinas, M; Cassano, T; Morgese, M G; Debonnel, G; Duranti, A; Tontini, A; Tarzia, G; Mor, M; Trezza, V; Goldberg, S R; Cuomo, V; Piomelli, D

    2005-12-20

    Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.

  20. Chronic antidepressant and clonidine treatment effects on conflict behavior in the rat.

    Science.gov (United States)

    Commissaris, R L; Ellis, D M; Hill, T J; Schefke, D M; Becker, C A; Fontana, D J

    1990-09-01

    The present studies examined the effects of chronic treatment with several antidepressants and clonidine on conflict behavior. In daily ten-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.25 or 0.5 mA). Electrification was signalled by a tone. Chronic desipramine (5 mg/kg, IP, b.i.d.) or clonidine (40 micrograms/kg, b.i.d.) treatment resulted in time-dependent anticonflict effects, with a latency to onset of approximately 3-4 weeks. In contrast, chronic buproprion (up to 10 mg/kg, IP, b.i.d.), mianserin (up to 10 mg/kg, IP, b.i.d.) or trazodone (up to 40 mg/kg, IP, b.i.d.) treatment resulted in at best only a weak anticonflict effect. The efficacy of these antidepressants and clonidine to increase punished responding when administered chronically correlates well with their efficacy as antipanic agents in man.

  1. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  2. Investigation of antidepressant mechanisms in an animal model of depression

    Energy Technology Data Exchange (ETDEWEB)

    Jesberger, J.A.

    1984-01-01

    The rat olfactory bulbectomy model has recently been found to exhibit good predictive properties when used to screen drugs for antidepressant activity, thereby suggesting that it may have a pathological defect particularly sensitive to the antidepressant activity of drugs. This model, with its well defined behavioral syndrome, was thus used to investigate some neurochemical effects of 4 species of antidepressant drugs and to see if drug actions varied between the normal and pathological states. A major finding in the study was the regional variation in /sup 3/H-imipramine binding and beta receptor density following the lesion. In addition treatment of normal rats with one of the 4 different antidepressant drugs caused changes in the density of /sup 3/H-imipramine recognition sites and beta receptors that varied between the 4 regions examined and with the drug administered such that none of the 4 drugs had identical response profiles. This suggests that the different drugs may be acting on different neurochemical substrates and that the distribution and sensitivity of the substrate varies for the different brain regions. Furthermore, results obtained in this investigation suggests that the effects of some antidepressant drugs on noradrenergic and serotonergic systems are markedly state-dependent and that this varies between different brain regions.

  3. Decisional conflict among women considering antidepressant medication use in pregnancy.

    Science.gov (United States)

    Walton, Georgia D; Ross, Lori E; Stewart, Donna E; Grigoriadis, Sophie; Dennis, Cindy-Lee; Vigod, Simone

    2014-12-01

    The purpose of this study was to examine decision-making among women considering antidepressant medication use in pregnancy. Decisional conflict was assessed using the Decisional Conflict Scale (DCS) among pregnant women considering antidepressant medication treatment (N = 40). Overall DCS and subscale scores were compared between women who were antidepressant users and non-users. Semi-structured interviews (N = 10) explored barriers and facilitators of decision-making. Twenty-one women (52 %) had moderate or high decisional conflict (DCS ≥ 25). Overall DCS scores did not differ between groups, but antidepressant use was associated with feeling more adequately informed (subscale mean 17.5, SD 17.9 vs. 42.1, SD 23.8, p = 0.001) and clear about values (subscale mean 16.7, SD 15.1 vs. 29.8, SD 24.0, p = 0.043). Barriers to decision-making were (1) difficulty weighing maternal versus infant health, (2) lack of high quality information, (3) negative external influences, and (4) emotional reactions to decision-making. Facilitators were (1) interpersonal supports, (2) accessible subspecialty care, and (3) severe depressive symptoms. Many pregnant women facing decisions regarding antidepressant medication use experience decisional conflict. Interventions that provide accurate information, assistance with weighing risks and benefits of treatment, management of problematic external influences, and emotional support may reduce decisional conflict and facilitate the decision-making process.

  4. Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants.

    Science.gov (United States)

    Italiano, Domenico; Spina, Edoardo; de Leon, Jose

    2014-11-01

    Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant. This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided if appropriate DI studies have been completed. More PK studies are needed for: i) antiepileptics with potent inductive effects for all recently approved antidepressants; ii) high doses of mild CYP3A4 inducers, such as clobazam, eslicarbazepine, oxcarbazepine, rufinamide and topiramate for reboxetine and vilazodone; iii) valproate as a possible inhibitor, mild inducer or both a mild inducer and competitive inhibitor of some antidepressants; and iv) inhibitory effects of long-term fluoxetine use on clobazam, lacosamide, phenobarbital, primidone, carbamazepine, felbamate, tiagabine and zonisamide. Possible synergistic or additive beneficial PD DIs in generalized anxiety disorder, chronic pain, migraine prophylaxis, weight control and menopausal symptoms need study.

  5. Association between antidepressants and falls in Parkinson's disease.

    Science.gov (United States)

    Martinez-Ramirez, Daniel; Giugni, Juan C; Almeida, Leonardo; Walz, Roger; Ahmed, Bilal; Chai, Fiona A; Rundle-Gonzalez, Valerie; Bona, Alberto R; Monari, Erin; Wagle Shukla, Aparna; Hess, Christopher W; Hass, Chris J; Okun, Michael S

    2016-01-01

    Parkinson's disease (PD) patients have an increased risk of falls resulting in important social and economical consequences. Risk factors for falls include the use of psychotropic drugs, which are used for the treatment of PD neuropsychiatric symptoms. We aimed to determine the association between psychotropic drug use and falls in a PD cohort. A cross-sectional study from the NPF QII study UF site was conducted. Subjects reported presence and frequency of falls in the prior year. Frequency was scored from 0 (no falls) to 4 (falling daily). Antidepressants, antipsychotics, cognitive enhancers/stimulants, and benzodiazepines were considered psychotropics. Forty percent of the 647 subjects included had a fall in the previous year. Fallers were found to have clinical signs of a more advanced disease. After adjusting for confounding variables, the regression analysis showed that use of antidepressants alone (adjusted OR 2.2, CI 95 % 1.3-3.8, p = 0.04), benzodiazepines alone (adjusted OR 2.0, CI 95 % 1.1-3.5, p = 0.02), and the combination of antidepressants with benzodiazepines (adjusted OR 4.1, CI 95 % 2.0-8.3, p antidepressants alone had a significantly higher mean frequency of falls score (1.07 vs. 0.44, p antidepressants was independently associated with falls in our PD cohort after considering for confounding variables such as age and measures of disease progression. Other factors related to disease progression should be considered before claiming the use of psychotropic drugs as causative.

  6. Peripheral administration of lactate produces antidepressant-like effects

    KAUST Repository

    Carrard, A

    2016-10-18

    In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

  7. Non-Antidepressant Long-term Treatment in Post-Traumatic Stress Disorder (PTSD).

    Science.gov (United States)

    Kerbage, Hala; Richa, Sami

    2015-01-01

    Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack empirical support. However, the most promising

  8. Antidepressant use and circulating prolactin levels.

    Science.gov (United States)

    Reeves, Katherine W; Okereke, Olivia I; Qian, Jing; Tworoger, Shelley S; Rice, Megan S; Hankinson, Susan E

    2016-07-01

    To determine whether antidepressants (AD), specifically selective serotonin reuptake inhibitors (SSRIs), are linked to elevated prolactin levels among the general population. Circulating prolactin levels were available for 4593 healthy participants in the Nurses' Health Study (NHS) and NHS2, including 267 AD users. We fit generalized linear models to calculate and compare adjusted mean prolactin levels between AD users and non-users and further among SSRI users. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for "elevated" prolactin levels (>11 ng/mL) comparing AD users to non-users. We evaluated AD use and change in prolactin levels among 610 NHS participants with two measurements an average of 11 years apart. Adjusted geometric mean prolactin levels were similar among SSRI users (13.2 ng/mL, 95 % CI 12.2-14.4), users of other classes of ADs (12.7 ng/mL, 95 % CI 11.0-14.6), and non-users (13.1 ng/mL, 95 % CI 12.8-13.4). Neither AD use (OR 1.17, 95 % CI 0.89-1.53) nor SSRI use (OR 0.95, 95 % CI 0.66-1.38) was associated with elevated prolactin levels. Change in prolactin levels was similar across women who started, stopped, consistently used, or never used ADs. This study does not support the hypothesis that AD use would influence breast cancer risk via altered prolactin levels. These results provide some evidence that use of ADs to treat depression or other conditions may not substantially increase prolactin levels in the majority of women.

  9. Antidepressant effect of taurine in diabetic rats.

    Science.gov (United States)

    Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

    2012-10-01

    Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  10. Association between antidepressant drug use during pregnancy and child healthcare utilisation

    NARCIS (Netherlands)

    Ververs, T. F.; van Wensen, K.; Freund, M. W.; van der Heide, M.; Visser, G. H. A.; Schobben, A. F. A. M.; de Jong-van den Berg, L. T. W.; Egberts, A. C. G.

    2009-01-01

    Objective To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group. Design Cohort study. Setting Health insurance records in the Netherlands.

  11. Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey

    NARCIS (Netherlands)

    Hamer, M.; Batty, G.D.; Seldenrijk, A.; Kivimaki, M.

    2011-01-01

    Aims: The association between antidepressant use and risk of cardiovascular disease (CVD) remains controversial, particularly in initially healthy samples. Given that antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are now prescribed not only for depression, but also for a

  12. Identifying genetic loci affecting antidepressant drug response in depression using drug-gene interaction models

    NARCIS (Netherlands)

    R. Noordam; C.L. Avery; L.E. Visser; B.H.Ch. Stricker (Bruno)

    2016-01-01

    textabstractAntidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify

  13. Indications for antidepressant drug prescribing in general practice in the Netherlands.

    NARCIS (Netherlands)

    Gardarsdottir, H.; Heerdink, E.R.; Dijk, L. van; Egberts, A.C.G.

    2007-01-01

    BACKGROUND: The intensity of the use of antidepressants in large populations can nowadays relatively easily be estimated using databases encompassing prescription data. There are shortcomings when using prescription databases as they contain no clinical data on patient illness. Antidepressants are

  14. Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex

    NARCIS (Netherlands)

    Lucassen, P.J.; Fuchs, E.; Czeh, B.

    2004-01-01

    BACKGROUND: Recent clinical and preclinical studies suggest that major depression may be related to impairments of structural plasticity. Consequently, antidepressants may act by restoring altered rates of cell birth or death. Here, we investigated whether the antidepressant tianeptine would affect

  15. Learning and memory in the forced swimming test: effects of antidepressants having varying degrees of anticholinergic activity.

    Science.gov (United States)

    Enginar, Nurhan; Yamantürk-Çelik, Pınar; Nurten, Asiye; Güney, Dilvin Berrak

    2016-07-01

    The antidepressant-induced reduction in immobility time in the forced swimming test may depend on memory impairment due to the drug's anticholinergic efficacy. Therefore, the present study evaluated learning and memory of the immobility response in rats after the pretest and test administrations of antidepressants having potent, comparatively lower, and no anticholinergic activities. Immobility was measured in the test session performed 24 h after the pretest session. Scopolamine and MK-801, which are agents that have memory impairing effects, were used as reference drugs for a better evaluation of the memory processes in the test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased immobility time suggesting impaired "learning to be immobile" in the animals. The test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg), moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg) decreased immobility time, which suggested that the drugs exerted antidepressant activity or the animals did not recall that attempting to escape was futile. The test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg) produced no effect on immobility time. Even though the false-negative and positive responses made it somewhat difficult to interpret the findings, this study demonstrated that when given before the pretest antidepressants with or without anticholinergic activity seemed to be devoid of impairing the learning process in the test.

  16. Effects of anti-depressants on olfactory sensitivity in mice.

    Science.gov (United States)

    Lombion, Sandrine; Morand-Villeneuve, Nadège; Millot, Jean-Louis

    2008-04-01

    Some studies have underlined a decrease in olfactory sensitivity in patients suffering from depression. The present study aims to evaluate the effects of current anti-depressant drugs on the olfactory sensitivity in mice. METHODS MICE: (N degrees =22) were tested in a Y-maze with a choice between an odorant (butanol) or distilled water before and during 3 weeks of daily intra-peritoneal injection of either citalopram or clomipramine. Their performance was compared with those of a control group (N degrees =11) injected with a saline solution. The results showed a significant decrease in olfactory sensitivity with both anti-depressants during the three weeks of treatment. The antidepressant induced alteration in serotonin and/or noradrenaline transmission in the olfactory bulb may account for the altered olfactory sensitivity observed in this study.

  17. Use of antidepressants and risk of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina S; Dehlendorff, Christian; Baandrup, Louise

    2017-01-01

    Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we...... identified all women (cases) aged 30-84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n = 4,103) and matched each case to 20 population controls (n = 58,706) by risk-set matching. Data on drug use (including tricyclic and related......-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other...

  18. Increased risk of antidepressant use in childhood cancer survivors

    DEFF Research Database (Denmark)

    Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

    2015-01-01

    AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage...... on the association between childhood cancer and antidepressant use indicated no modifying effect. CONCLUSION: Childhood cancer survivors should be followed-up for depression. Our results indicate an increasing need for follow-up especially in survivors treated by more recent, intensive anticancer treatment....... to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer...

  19. [On the proposed mechanism of action of antidepressants (author's transl)].

    Science.gov (United States)

    Le Fur, G

    1980-01-01

    Classical antidepressants (MAOI, uptake inhibitors) increase monoamine levels in the synaptic cleft. However other presynaptic mechanisms of action have been proposed: increase in release (amineptin), blockade of presynaptic alpha-adrenoceptors (mianserin). A postsynaptic approach is also possible: stimulation of beta-receptor (salbutamol), blockade of muscarinic receptor (quinupramine). Moreover the side effects have been correlated to a blockade of postsynaptic receptors: alpha 1 for aorthostatic hypotension, H1 for sedation and muscarinic for anticholinergic effects. However these effects do not explain the delay for the clinical efficiency of antidepressants. A desensitization of presynaptic receptors or a decrease in beta-postsynaptic receptors have been advanced. In fact a possible pharmacokinetic explanation for the delay of clinical efficiency, i.e. the necessary delay to reach brain steady state level, is possible. Finally the presence of imipramine binding sites might be a new approach of the mechanism of action of antidepressants.

  20. Cardiovascular Considerations in Antidepressant Therapy: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Habibeh Yekehtaz

    2015-10-01

    Full Text Available There is a definite correlation between cardiovascular diseases and depressive disorders. Nevertheless, many aspects of this association have yet to be fully elucidated. Up to half of coronary artery disease patients are liable to suffer from some depressive symptoms, with approximately 20% receiving a diagnosis of major depressive disorders. Pharmacotherapy is a key factor in the management of major depression, not least in patients with chronic diseases who are likely to fail to show proper compliance and response to non-pharmacological interventions. Antidepressants are not deemed completely safe. Indeed, numerous side effects have been reported with the administration of antidepressants, among which cardiovascular adverse events are of paramount importance owing to their disabling and life-threatening nature. We aimed to re-examine some of the salient issues in antidepressant therapy vis-à-vis cardiovascular considerations, which should be taken into account when prescribing such medications.

  1. Antidepressant exposure during early pregnancy and congenital malformations

    DEFF Research Database (Denmark)

    Pedersen, Lars Henning

    Pharmacological treatment of pregnant women with depression is hampered by concerns for the developing fetus. The presentation will summarize existing knowledge on the potential association between antidepressants and congenital malformations, elaborate on the scientific background, and discuss...... the clinical significance. Most information on malformations in humans is derived from epidemiological studies. The strengths and limitations of the different designs need careful consideration, including issues of confounding by indication, recall bias, and power. For most antidepressants existing data...... are reassuring, however, an association with heart malformations has been suggested for e.g. paroxetine. A potential biological explanation will be reviewed. The potential teratogenic potential of antidepressants needs to be balanced against the obvious problems associated with under-treated maternal depression...

  2. Use of anti-depressants and the risk of fracture of the hip or femur

    OpenAIRE

    van den Brand, M. W. M.; Samson, M. M.; Pouwels, S.; van Staa, T. P.; Thio, B.; Cooper, C.; Leufkens, H. G. M.; Egberts, A. C. G.; Verhaar, H. J. J.; de Vries, F.

    2009-01-01

    Summary Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Introduction Anti-depressants are known to have serious side effects. We examined the association between t...

  3. Age-related response to redeemed antidepressants measured by completed suicide in older adults

    DEFF Research Database (Denmark)

    Erlangsen, Annette; Conwell, Yeates

    2014-01-01

    antidepressant prescriptions during the last months of life than younger persons. CONCLUSION: An age-dependent decline in suicide rate for antidepressant recipients was identified. One reason could be that older adults respond better to antidepressants than younger age groups. Still, the increasing gap with age...... between estimated prevalence of depression and antidepressant prescription rate in persons dying by suicide underscores the need for assessment of depression in the oldest old....

  4. Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L

    OpenAIRE

    El-Alfy, Abir T.; Ivey, Kelly; Robinson, Keisha; Ahmed, Safwat; Radwan, Mohamed; Slade, Desmond; Khan, Ikhlas; ElSohly, Mahmoud; Ross, Samir

    2010-01-01

    The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Δ9-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lac...

  5. Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials.

    Science.gov (United States)

    Tedeschini, Enrico; Levkovitz, Yeciel; Iovieno, Nadia; Ameral, Victoria E; Nelson, J Craig; Papakostas, George I

    2011-12-01

    (age 55 and older; P design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MDD patients. The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear. © Copyright 2011 Physicians Postgraduate Press, Inc.

  6. Risk of drug interaction: combination of antidepressants and other drugs

    Directory of Open Access Journals (Sweden)

    Miyasaka Lincoln Sakiara

    2003-01-01

    Full Text Available OBJECTIVE: To assess the frequency of combination of antidepressants with other drugs and risk of drug interactions in the setting public hospital units in Brazil. METHODS: Prescriptions of all patients admitted to a public hospital from November 1996 to February 1997 were surveyed from the hospital's data processing center in São Paulo, Brazil. A manual search of case notes of all patients admitted to the psychiatric unit from January 1993 to December 1995 and all patients registered in the affective disorders outpatient clinic in December 1996 was carried out. Patients taking any antidepressant were identified and concomitant use of drugs was checked. By means of a software program (Micromedex® drug interactions were identified. RESULTS: Out of 6,844 patients admitted to the hospital, 63 (0.9% used antidepressants and 16 (25.3% were at risk of drug interaction. Out of 311 patients in the psychiatric unit, 63 (20.2% used antidepressants and 13 of them (20.6% were at risk. Out of 87 patients in the affective disorders outpatient clinic, 43 (49.4% took antidepressants and 7 (16.2% were at risk. In general, the use of antidepressants was recorded in 169 patients and 36 (21.3% were at risk of drug interactions. Twenty different forms of combinations at risk of drug interactions were identified: four were classified as mild, 15 moderate and one severe interaction. CONCLUSION: In the hospital general units the number of drug interactions per patient was higher than in the psychiatric unit; and prescription for depression was lower than expected.

  7. How does media coverage effect the consumption of antidepressants? A study of the media coverage of antidepressants in Danish online newspapers 2010-2011.

    Science.gov (United States)

    Green Lauridsen, Michael; Kälvemark Sporrong, Sofia

    2017-08-02

    The news media has become a major source of health information for the public, and hence vital in the individuals' opinions and decisions about health topics. The first decrease in the usage of antidepressants in Denmark in over a decade happened alongside an intensive period of media coverage about antidepressants. The aim of this study was to examine the Danish media's coverage of antidepressants during 2010-2011 in order to explore what influence it could have had on the change in the use of antidepressants. Three media theoretical concepts, agenda-setting, priming and framing, were used to explain the media influence with regard to which subject the public should think about, which criteria the public should judge the subject by, and how the public should think about the subject. All articles about antidepressants in the main Danish Internet newspapers from 2010-2011 were analyzed via quantitative and qualitative content analyses. The quantitative analysis was used to determine agenda-setting (number of articles) and, by coding articles, how priming was used in the descriptions of antidepressants. In the qualitative analysis, all articles were analyzed and condensed to determine which frames were used. Quantitative results: 271 articles were included. Agenda-setting was shown by a marked increase in the number of articles about antidepressants. Eight main codes were identified, with the negatively-associated side effects being the major one, thereby priming the public to use side effects as a criterion when judging antidepressants. Qualitative results: Two main frames were identified: 1) economic profits vs. medicine safety, and 2) the necessity of antidepressants. Both frames presented a critical view on antidepressants. It is believed that the media's agenda-setting, priming and framing of antidepressants led the public to have a more skeptical view on antidepressants, which may have probably contributed to a decrease in the usage of antidepressants

  8. Depression during pregnancy: views on antidepressant use and information sources of general practitioners and pharmacists.

    NARCIS (Netherlands)

    Ververs, T.; Dijk, L. van; Yousofi, S.; Schobben, F.; Visser, G.H.A.

    2009-01-01

    Background: The use of antidepressants during pregnancy has increased in recent years. In the Netherlands, almost 2% of all pregnant women are exposed to antidepressants. Although guidelines have been developed on considerations that should be taken into account, prescribing antidepressants during

  9. Prenatal exposure to antidepressants and risk of epilepsy in childhood.

    Science.gov (United States)

    Mao, Yanyan; Pedersen, Lars Henning; Christensen, Jakob; Vestergaard, Mogens; Zhou, Weijin; Olsen, Jørn; Sun, Yuelian

    2016-11-01

    This study aimed to estimate the association between prenatal exposure to antidepressants and risk of epilepsy in childhood, taking maternal depression into account. We conducted a population-based cohort study including all Danish singletons born alive between 1997 and 2008 (n = 734 237). Information on antidepressant medication and diagnosis of depression and epilepsy was obtained from Danish National Registers. The exposed group comprised children of mothers who used antidepressants from 30 days before pregnancy until the date of birth. The reference group comprised children of mothers who used no antidepressants from 6 months before pregnancy to birth. We estimated the hazard ratios (HR) of epilepsy and 95% confidence intervals (CI) using Cox proportional hazard models. We identified 12 438 (1.7%) children exposed to antidepressants during pregnancy (including 30 days before pregnancy) and 5829 (0.8%) children diagnosed with epilepsy in the follow-up time (mean: 6.7 years). Children exposed to antidepressants during pregnancy had a 27% higher risk of epilepsy (aHR: 1.27; 95%CI: 1.05-1.54) than children in the reference group. The estimate of this association was 1.71 (95%CI: 1.10-2.66) if their mothers also had a registry-based hospital diagnosis of depression in the 6 months before pregnancy or during pregnancy and 1.14 (95%CI: 0.91-1.43) if their mothers had no registry-based hospital diagnosis of depression. Children of mothers who used antidepressants from 2 to 6 months before pregnancy (but not during pregnancy) had an increased risk of epilepsy (aHR: 1.36; 95%CI: 1.07-1.73). Antidepressant use during pregnancy was associated with a higher risk of epilepsy among children whose mothers had also a registry-based hospital diagnosis of depression during pregnancy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  11. Association between mortality from suicide in England and antidepressant prescribing: an ecological study

    Directory of Open Access Journals (Sweden)

    Majeed Azeem

    2004-12-01

    Full Text Available Abstract Background Antidepressant prescribing has been increasing in England. Studies in other countries suggest that while this may be associated with reduced suicide rates, it may also be associated with increased fatal poisoning from antidepressant drugs. We therefore conducted an ecological study to assess the association between prescription rates for antidepressants and suicide or fatal antidepressant-related poisoning in England. Methods The Office for National Statistics provided information on the number of suicides, antidepressant-related poisoning deaths and populations for England between 1993 and 2002. The Department of Health supplied data on prescriptions for all antidepressants dispensed in England. Associations between prescriptions and deaths were assessed using Spearman's rank correlation coefficient. Results There were 46,747 suicides, 3,987 deaths involving tricyclic antidepressants and 430 involving selective serotonin re-uptake inhibitors and other antidepressants. Increased antidepressant prescribing was statistically associated with a fall in suicide rates (Spearman's rs = -0.73, p = 0.02 and fatal poisoning involving tricyclic antidepressants (rs = -0.64, p = 0.05. In contrast, increased prescribing of selective serotonin re-uptake inhibitors and other antidepressants was statistically associated with an increase in fatal poisoning involving these drugs (rs = 0.99, p Conclusion Increased prescribing of antidepressants may indicate improved diagnosis and treatment of depression in primary care. Our analysis suggests that this was accompanied by lower suicide rates. A decrease in poisoning deaths involving tricyclic antidepressants may suggest a change in preference for using serotonin reuptake inhibitors and other antidepressant drugs for high-risk patients. This may also partially explain the increase in deaths involving these drugs. Due to the ecological nature of the design, we cannot say conclusively whether reduced

  12. Antidepressant-like effect of peony glycosides in mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Ip, Siu-Po; Tsai, Sam-Hip; Che, Chun-Tao

    2008-09-26

    The root part of Paeonia lactiflora Pall. (Ranunculaceae), known as peony, is often used in Chinese herbal formulae for the treatment of depression-like disorders. Previous studies in our laboratory have shown that an ethanol extract of peony produced antidepressive effects in mouse models of depression. It is well known that peony contains glycosides such as paeoniflorin and albiflorin, yet it remains unclear whether the total glycosides of peony (TGP) are effective. The present study aims to evaluate the antidepressant-like effects of TGP. The antidepressant-like effects of TGP was determined by using animal models of depression including forced swim and tail suspension tests. The acting mechanism was explored by determining the effect of TGP on the activities of monoamine oxidases. Intragastric administration of TGP at 80 and 160 mg/kg for seven days caused a significant reduction of immobility time in both forced swim and tail suspension tests, yet TGP did not stimulate locomotor activity in the open-field test. In addition, TGP treatment antagonized reserpine-induced ptosis and inhibited the activities of monoamine oxidases in mouse cerebrum. These results suggest that the antidepressive effects of TGP are mediated, at least in part, by the inhibition of monoamine oxidases.

  13. Antidepressant and antioxidant activities of Artemisia absinthium L ...

    African Journals Online (AJOL)

    Artemisia absinthium (Asteraceae) is widely used in Iranian traditional medicine. Its effects may be correlated with the presence of antioxidant compounds. Methanolic extract of A. absinthium aerial part at flowering stage was screened for antioxidant activities by five complementary test systems. Also, its antidepressant ...

  14. Antidepressant and antioxidant activities of Artemisia absinthium L ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-15

    Dec 15, 2009 ... Mora S, Millıan R, Lungenstrass H, Dııaz-Vıeliz G, Morıan JA, Herrera-. Ruiz M, Tortoriello J (2006). The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats. J. Ethnopharmacol. 106: 76-81. Morteza-Semnani K, Mahmoudi M, Riahi G (2007). Effects of essential.

  15. Suicides in Adolescents: Benefit/Harm Balance of Antidepressants

    Science.gov (United States)

    Saz, Ulas Eylem; Arslan, Mehmet Tayyip; Egemen, Ayten

    2007-01-01

    Introduction: Depression is an important cause of suicide in adolescents. It has been speculated that antidepressants themselves can increase the risk of suicide. Method: Cases of adolescents admitted to the Ege University Pediatric Emergency Department in Turkey due to suicide attempt were assessed. Results: Nine of 13 suicide attempts during…

  16. Anti-depressants in primary care: analysis of treatment discontinuations.

    Science.gov (United States)

    McGettigan, P; Kelly, A; Carvahlo, M; Feely, J

    2000-11-01

    It is well known that adherence to anti-depressant therapy is often poor, but the literature describes little in the way of systematic analyses to determine co-relation between treatment discontinuation and possible contributing factors. We used a community dispensing database to review anti-depressant prescribing patterns and continuity of therapy over a period of 10 months among a population of community-based general practice patients. Some 109,228 anti-depressant prescriptions were dispensed to 24,073 patients, of whom 37.5% collected a single prescription only. Tricyclic anti-depressant prescribing declined significantly during the observation period (from 70% of prescriptions in month 1 to 66% in month 10) while that of selective serotonin reuptake inhibitors (SSRIs) increased (23% in month 1, 28% in month 10) ( p 1 prescription, adherence was poor and declined over time. The factors that influenced the extent to which patients failed to adhere to therapy included dosage level (% DDD) and age ( p <0.0001 for both), but not drug class or sex. The findings suggest that low dosage is a contributory factor in treatment discontinuation, and that contrary to common perception, SSRIs are not necessarily associated with better adherence to therapy than tricyclics. Copyright (c) 2000 John Wiley & Sons, Ltd.

  17. Antidepressants and suicide in children and adolescents: a storm in ...

    African Journals Online (AJOL)

    Paediatric psychopharmacology has entered a new and exciting era, with a substantial increase in the number of randomised controlled trials in paediatric mood and anxiety disorders. Although not a child and adolescent psychiatrist, I have followed the recent controversies and negative press surrounding antidepressants ...

  18. Managing antidepressants in primary care: physicians' treatment modifications.

    Science.gov (United States)

    Tamburrino, Marijo B; Nagel, Rollin W; Lynch, Denis J

    2011-06-01

    To examine antidepressant management practices in primary care, patients (N = 148) given an antidepressant for at least one month completed the Beck Depression Inventory (BDI-II), the Patient Health Questionnaire-9 (PHQ-9), and a demographic survey. Participants' mean age was 50.7 yr. and 80% were women. Patients' charts indicated whether physicians had made changes to prescribed antidepressants or dose either 6 wk. before or 6 wk. after study entry. For the 87% of participants whose depression status could be determined, 10% met dysthymic disorder criteria and only 33% had had a medication change in the previous month. Major depressive disorder occurred in 37% but only 18% had had a medication change. Co-existing dysthymic disorder and major depressive disorder were diagnosed in 34%, with 24% receiving a medication change. Participants not receiving a medication change had mean BDI-II scores indicating moderate depression. Lack of antidepressant adjustment suggests physicians may need to monitor depressive symptoms closely using protocols and prompts.

  19. Antidepressant use during pregnancy and asthma in the offspring

    DEFF Research Database (Denmark)

    Liu, Xiaoqin; Olsen, Jørn; Pedersen, Lars Henning

    2015-01-01

    BACKGROUND AND OBJECTIVES: It has been suggested that maternal depression during pregnancy is abstract associated with asthma in the offspring, but the role of medical treatment of depression is not known. Our goal was to examine whether prenatal antidepressant use increases the risk of asthma in...

  20. Effect of nifedipine, imipramine and sertraline on the antidepressant ...

    African Journals Online (AJOL)

    The objective of the study was to determine the effect of nifedipine, imipramine and sertraline on the acute and long-term antidepressant-like responses of furosemide in the forced swim (FST) and tail suspension (TST) tests in mice. Groups of mice of six in each group were treated for 30 days with Tween 80, furosemide (10 ...

  1. Antidepressant-like Potentials of Buchholzia Coriacea Seed Extract ...

    African Journals Online (AJOL)

    olayemitoyin

    amygdala, and thalamus (Drevets et al., 2002). Together, these ... critical role in learning and memory, the hippocampus is one of the ..... stress. Eur J Pharmacol; 371:113-122. Malberg, J. E, Eisch, A. J, Nestler, E. J, Duman, R. S. (2000). Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.

  2. Economic impact of antidepressant treatment duration in naturalistic conditions.

    Science.gov (United States)

    Tournier, M; Crott, R; Gaudron, Y; Verdoux, H

    2013-05-01

    To assess the economic impact of the duration of antidepressant drug treatment in a real-life setting. A historical fixed cohort study included 27 917 patients aged 18 and over with a new antidepressant treatment registered in the national insurance database. The economic impact concerned healthcare expenditure in the first 3 months after treatment discontinuation. Generalized linear models were used to compare two groups of treatment duration: adjustment for care costs before and during treatment episode, gender, age, chronic diseases, welfare and prescriber specialty, total healthcare costs (in log) [-0.06 (-0.14;0.01) P = 0.11] and psychiatric care costs (in square root) [-0.08 (-0.41;0.25) P = 0.6] were similar in both groups. Non-psychiatric care costs were significantly lower in the 'long treatment duration' group compared with the 'short treatment duration' group [-11.4 (-15.8; -7.0) P costs over the antidepressant treatment episode were larger in the 'long treatment duration' group compared with the 'short treatment duration' group. With regard to healthcare costs and global health, antidepressant drug treatments of short duration appear less effective than treatment of recommended duration. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  3. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

  4. Qualitative study of the influence of antidepressants on the ...

    African Journals Online (AJOL)

    Qualitative study of the influence of antidepressants on the psychological health of patients on antiretroviral therapy in Uganda. ... Although depressive experience among the patients was largely described in terms of criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), some of the symptoms ...

  5. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose

    NARCIS (Netherlands)

    Monteban-Kooistra, W; van den Berg, M; Tulleken, J; Ligtenberg, J; Zijlstra, J; Meertens, J.

    Objective:The Brugada syndrome is a clinical and electrocardiographic familial entity, which may lead to sudden cardiac death. A Brugada pattern ECG may occasionally be caused by conditions such as an overdose of tricyclic antidepressants (TCA). Toxicity of TCA frequently results in the need for

  6. Antidepressant-induced acute colonic (pseudo) obstruction (Ogilvie syndrome)

    Science.gov (United States)

    Ghorpade, V.A.P.

    2005-01-01

    Patients on antidepressant drugs commonly complain of dryness of the mouth, tremors, blurring of vision and constipation, which are attributed to the anticholinergic action of the drugs. We report two cases of gastrointestinal complications (pseudo-intestinal obstruction), which are considered rare according to a review of the literature. This condition is also known as Ogilvie syndrome.

  7. Evaluation of the antidepressant activity of methanol extract and ...

    African Journals Online (AJOL)

    Antidepressant activity of the methanol extract, aqueous and chloroform fractions was evaluated using the forced swim and tail suspension tests at doses of 50, 100 and 200 mg/kg with imipramine (15 mg/kg) as the standard drug. Changes in body weights and organ weight ratio were also evaluated following treatment with ...

  8. The analgesic effect of different antidepressants combined with ...

    African Journals Online (AJOL)

    Background: Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice. Methods: Different groups of six ...

  9. Pharmacological Experimental Study Of The Anti-Depressant Effect ...

    African Journals Online (AJOL)

    Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...

  10. The Antidepressant-Like Actions of Furosemide, Bumetanide and ...

    African Journals Online (AJOL)

    The effects on down-stream signalling and neuroplasticity are the ways the actions of the presently-used antidepressants, the tricarboxylic acids (TCAs) and the selective serotonin reuptake inhibitors (SSRIs) are enhanced and effected. The present study aims to determine whether the actions of the calcium channel blocker, ...

  11. Antidepressant Use among Persons Aged 12 and Over: United States, 2011-2014. NCHS Data Brief. Number 283

    Science.gov (United States)

    Pratt, Laura A.; Brody, Debra J.; Gu, Qiuping

    2017-01-01

    Antidepressants are one of the three most commonly used therapeutic drug classes in the United States. While the majority of antidepressants are taken to treat depression, antidepressants can also be taken to treat other conditions, like anxiety disorders. This Data Brief provides the most recent estimates of antidepressant use in the U.S.…

  12. Antidepressant exposure in pregnancy and risk of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Sørensen MJ

    2013-11-01

    Full Text Available Merete Juul Sørensen,1 Therese Koops Grønborg,2 Jakob Christensen,3,4 Erik Thorlund Parner,2 Mogens Vestergaard,5,6 Diana Schendel,7 Lars Henning Pedersen8,9 1Regional Centre of Child and Adolescent Psychiatry, Aarhus University Hospital, Risskov, Denmark; 2Department of Public Health, Section of Biostatistics, Aarhus University, Aarhus, Denmark; 3Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Pharmacology, 5Department of Public Health, Section of General Practice, 6Research unit for General Practice, Aarhus University, Aarhus, Denmark; 7Centers for Disease Control and Prevention, Atlanta, GA, USA; 8Danish Epidemiological Science Centre, Institute of Public Health, 9Department of Obstetrics and Gynecology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark Background: Both the use of antidepressant medication during pregnancy and the prevalence of autism spectrum disorder have increased during recent years. A causal link has recently been suggested, but the association may be confounded by the underlying indication for antidepressant use. We investigated the association between maternal use of antidepressant medication in pregnancy and autism, controlling for potential confounding factors. Methods: We identified all children born alive in Denmark 1996–2006 (n=668,468 and their parents in the Danish Civil Registration System. We obtained information on the mother's prescriptions filled during pregnancy from the Danish National Prescription Registry, and on diagnoses of autism spectrum disorders in the children and diagnoses of psychiatric disorders in the parents from the Danish Psychiatric Central Register. In a cohort analysis, we estimated hazard ratios of autism spectrum disorders in children exposed to antidepressant medication during pregnancy compared with children who were not exposed, using Cox proportional hazards regression analysis. Furthermore, we estimated the risk

  13. Newer generation antidepressants for depressive disorders in children and adolescents.

    Science.gov (United States)

    Hetrick, Sarah E; McKenzie, Joanne E; Cox, Georgina R; Simmons, Magenta B; Merry, Sally N

    2012-11-14

    Depressive disorders are common in young people and are associated with significant negative impacts. Newer generation antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are often used, however evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour. To determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of newer generation antidepressants compared with placebo in the treatment of depressive disorders in children and adolescents. For this update of the review, we searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We searched clinical trial registries and pharmaceutical company websites. We checked reference lists of included trials and other reviews, and sent letters to key researchers and the pharmaceutical companies of included trials from January to August 2011. Published and unpublished randomised controlled trials (RCTs), cross-over trials and cluster trials comparing a newer generation antidepressant with a placebo in children and adolescents aged 6 to 18 years old and diagnosed with a depressive disorder were eligible for inclusion. In this update, we amended the selection criteria to include newer generation antidepressants rather than SSRIs only. Two or three review authors selected the trials, assessed their quality, and extracted trial and outcome data. We used a random-effects meta-analysis. We used risk ratio (RR) to summarise dichotomous outcomes and mean difference (MD) to summarise continuous measures

  14. The monitoring of longer term prescriptions of antidepressants: observational study in a primary care setting.

    Science.gov (United States)

    Sinclair, Jennifer E; Aucott, Lorna S; Lawton, Kenneth; Reid, Ian C; Cameron, Isobel M

    2014-08-01

    There is little evidence to guide the frequency of review for patients taking antidepressants in the longer term. To measure the frequency with which patients on longer term courses of antidepressants have their treatment monitored in primary care and to identify patient characteristics associated with the frequency of monitoring. A cohort of patients who were receiving antidepressants continuously for at least two years was identified from four general practices. Data were collected from patients' general medical records. The dates of all GP consultations and whether they included a documented review of antidepressant therapy were recorded, along with patient characteristics hypothesized to influence the frequency of monitoring. The frequency of antidepressant review consultations and proportion of participants being reviewed during a specific year of antidepressant therapy decreased with increasing year of antidepressant therapy. Individuals who receive antidepressants for an overt mental health reason; undergo more dose and drug changes; and who are referred to the community mental health team have their antidepressant therapy reviewed more often during the first five years of antidepressant therapy. As many patients on longer term courses of antidepressants are not being appropriately reviewed, a 'chronic disease management approach' to depression in primary care is advocated. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Antidepressant sales and regional variations of suicide mortality in Germany.

    Science.gov (United States)

    Blüml, Victor; Helbich, Marco; Mayr, Michael; Turnwald, Roland; Vyssoki, Benjamin; Lewitzka, Ute; Hartung, Sebastian; Plener, Paul L; Fegert, Jörg M; Kapusta, Nestor D

    2017-04-01

    Suicides account for over one million deaths per year worldwide with depression among the most important risk factors. Epidemiological research into the relationship between antidepressant utilization and suicide mortality has shown heterogeneous and contradictory results. Different methodological approaches and limitations could at least partially explain varying results. This is the first study assessing the association of suicide mortality and antidepressant sales across Germany using complex statistical approaches in order to control for possible confounding factors including spatial dependency of data. German suicide counts were analyzed on a district level (n = 402) utilizing ecological Poisson regressions within a hierarchical Bayesian framework. Due to significant spatial effects between adjacent districts spatial models were calculated in addition to a baseline non-spatial model. Models were adjusted for several confounders including socioeconomic variables, quality of psychosocial care, and depression prevalence. Separate analyses were performed for Eastern and Western Germany and for different classes of antidepressants (SSRIs and TCAs). Overall antidepressant sales were significantly negatively associated with suicide mortality in the non-spatial baseline model, while after adjusting for spatially structured and unstructured effects the association turned out to be insignificant. In sub-analyses, analogue results were found for SSRIs and TCAs separately. Suicide risk shows a distinct heterogeneous pattern with a pronounced relative risk in Southeast Germany. In conclusion, the results reflect the heterogeneous findings of previous studies on the association between suicide mortality and antidepressant sales and point to the complexity of this hypothesized link. Furthermore, the findings support tailored suicide preventive efforts within high risk areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Serotonin Transporter-Independent Actions of the Antidepressant Vortioxetine As Revealed Using the SERT Met172 Mouse.

    Science.gov (United States)

    Nackenoff, Alex G; Simmler, Linda D; Baganz, Nicole L; Pehrson, Alan L; Sánchez, Connie; Blakely, Randy D

    2017-05-17

    Selective serotonin (5-HT, SERT) reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression. However, they have delayed efficacy and can induce side-effects that can encourage discontinuation. Recently, agents have been developed, including vortioxetine (Trintellix), that augment SERT blockade with interactions at other targets. At therapeutic doses, vortioxetine interacts with SERT as well as 5-HT 1A , 5-HT 1B , 5-HT 3 , and 5-HT 7 receptors. We assessed the SERT-dependency of vortioxetine action using the SERT Met172 mouse model, which disrupts high-affinity interactions of many antidepressants with the transporter. We demonstrate that the SERT Met172 substitution induces an ∼19-fold loss in vortioxetine potency for SERT inhibition in midbrain synaptosomes. Moreover, in these mice, we observed reduced SERT occupancy, a diminished ability to prolong 5-HT clearance, and a reduced capacity to elevate extracellular 5-HT. Despite reduced interactions with SERT, vortioxetine maintained its ability to enhance mobility in tail suspension and forced swim tests, reduce consumption latency in the novelty induced hypophagia test, and promoted proliferation and survival of subgranular zone hippocampal stem cells. Our findings suggest that the antidepressant actions of vortioxetine may be SERT-independent, and encourage consideration of agents that mimic one or more actions of the drug in the development of improved depression treatments.

  17. The Effect of Serotonin-Targeting Antidepressants on Neurogenesis and Neuronal Maturation of the Hippocampus Mediated via 5-HT1A and 5-HT4 Receptors

    Directory of Open Access Journals (Sweden)

    Eri Segi-Nishida

    2017-05-01

    Full Text Available Antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs specifically increase serotonin (5-HT levels in the synaptic cleft and are widely used to treat mood and anxiety disorders. There are 14 established subtypes of 5-HT receptors in rodents, each of which has regionally different expression patterns. Many preclinical studies have suggested that the hippocampus, which contains abundant 5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG, is critically involved in the mechanisms of action of antidepressants. This review article will analyze studies demonstrating regulation of hippocampal functions and hippocampus-dependent behaviors by SSRIs and similar serotonergic agents. Multiple studies indicate that 5-HT1A and 5-HT4 receptor signaling in the DG contributes to SSRI-mediated promotion of neurogenesis and increased neurotrophic factors expression. Chronic SSRI treatment causes functions and phenotypes of mature granule cells (GCs to revert to immature-like phenotypes defined as a “dematured” state in the DG, and to increase monoamine reactivity at the dentate-to-CA3 synapses, via 5-HT4 receptor signaling. Behavioral studies demonstrate that the 5-HT1A receptors on mature GCs are critical for expression of antidepressant effects in the forced swim test and in novelty suppressed feeding; such studies also note that 5-HT4 receptors mediate neurogenesis-dependent antidepressant activity in, for example, novelty-suppressed feeding. Despite their limitations, the collective results of these studies describe a potential new mechanism of action, in which 5-HT1A and 5-HT4 receptor signaling, either independently or cooperatively, modulates the function of the hippocampal DG at multiple levels, any of which could play a critical role in the antidepressant actions of 5-HT-enhancing drugs.

  18. Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study.

    Science.gov (United States)

    Baldomero, E Baca; Ubago, J Giner; Cercós, C Leal; Ruiloba, J Vallejo; Calvo, C García; López, R Prieto

    2005-01-01

    Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant. This randomized, open-label, multicenter study compared the effectiveness of the SNRI venlafaxine extended release (VXR) with that of conventional antidepressants (CA) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting. Patients with a Hamilton Depression Rating Scale (HAM-D17) score > or =17 were randomly assigned to treatment with an alternative CA or VXR. Remission was defined as a score < or =7 on the HAM-D17. Efficacy analyses were carried out on 3,097 patients from the intent-to-treat (ITT) population (1,632 VXR; 1,465 CA). The antidepressants prescribed most frequently in the CA group were paroxetine (21.3%), citalopram (20.1%), sertraline (19.1%), fluoxetine (17.0%), and mirtazapine (7.9%). After 24 weeks of treatment, the VXR group demonstrated a significantly higher remission rate than did the CA group (59.3% VXR; 51.5% CA; P<.0001; odds ratio: 1.37; 95% CI: 1.19-1.58; P<.01). Despite the limitations of the open design, the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant.

  19. The Antidepressant 5-HT2A Receptor Antagonists Pizotifen and Cyproheptadine Inhibit Serotonin-Enhanced Platelet Function

    Science.gov (United States)

    Lin, Olivia A.; Karim, Zubair A.; Vemana, Hari Priya; Espinosa, Enma V. P.; Khasawneh, Fadi T.

    2014-01-01

    There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR) expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS) exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and EMD 281014, their

  20. The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function.

    Science.gov (United States)

    Lin, Olivia A; Karim, Zubair A; Vemana, Hari Priya; Espinosa, Enma V P; Khasawneh, Fadi T

    2014-01-01

    There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR) expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS) exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and EMD 281014, their

  1. The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function.

    Directory of Open Access Journals (Sweden)

    Olivia A Lin

    Full Text Available There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and

  2. Does negative affectivity predict differential response to an SSRI versus a non-SSRI antidepressant?

    Science.gov (United States)

    Gerra, Maria Lidia; Marchesi, Carlo; Amat, Jose A; Blier, Pierre; Hellerstein, David J; Stewart, Jonathan W

    2014-09-01

    This work tested the hypothesis that patients with high negative affectivity (NA) would have a better response to a serotonergic agent (escitalopram) than to one not thought to act directly on serotonin (bupropion). Data from a study conducted between August 2007 and July 2011 were reanalyzed retrospectively. Patients (N = 245) meeting criteria for major depressive disorder (MDD), diagnosed with DSM-IV-TR, were randomly assigned to double-blind treatment with bupropion extended-release, escitalopram, or the combination. Negative affectivity score was estimated using the guilt, hostility/irritability, and fear/anxiety items of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Quick Inventory of Depressive Symptoms, and the Social Adjustment Scale. We felt that these items captured published descriptions of the NA construct. A Clinical Global Impressions-Severity of Illness (CGI-S) score ≤ 2 defined response. Because combined treatment addressed both serotonin and non-serotonin systems, patients treated with both medications did not test the hypothesis and so were excluded from the analyses. Analysis of covariance with treatment as a grouping variable, NA as covariate, and CGI-S as dependent variable showed a significant 2-way interaction between treatment and NA (F₁,₁₅₆ = 4.82, P affectivity respond preferentially to antidepressants that selectively enhance serotonin neurotransmission. Although patients with low NA appear to benefit from serotonin enhancement as well, they also improved with bupropion, an antidepressant not thought to directly affect serotonin neurotransmission. These findings come from retrospective analyses using unproven approximation of NA, so no clinical inferences should be made before independent replication utilizing accepted NA measurement. ClinicalTrials.gov identifier: NCT00519428. © Copyright 2014 Physicians Postgraduate Press, Inc.

  3. Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study.

    Science.gov (United States)

    Gallagher, Patience J; Castro, Victor; Fava, Maurizio; Weilburg, Jeffrey B; Murphy, Shawn N; Gainer, Vivian S; Churchill, Susanne E; Kohane, Isaac S; Iosifescu, Dan V; Smoller, Jordan W; Perlis, Roy H

    2012-10-01

    OBJECTIVE It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system. METHOD Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed. RESULTS NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21-2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables. CONCLUSIONS These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding.

  4. Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands : choice of antidepressant and dose

    NARCIS (Netherlands)

    de Vries, Ymkje Anna; de Jonge, Peter; Kalverdijk, Luuk; Bos, Jens H. J.; Schuiling-Veninga, Catharina C. M.; Hak, Eelko

    2016-01-01

    The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended.

  5. Antidepressants for depression in adults with HIV infection.

    Science.gov (United States)

    Eshun-Wilson, Ingrid; Siegfried, Nandi; Akena, Dickens H; Stein, Dan J; Obuku, Ekwaro A; Joska, John A

    2018-01-22

    Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population. To assess the efficacy of antidepressant therapy for treatment of depression in PLWH. We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017. We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria. Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach. We included 10 studies

  6. Transcranial magnetic stimulation as an antidepressant alternative in a patient with Brugada syndrome and recurrent syncope.

    Science.gov (United States)

    Alampay, Miguel M; Haigney, Mark C; Flanagan, Michael C; Perito, Robert M; Love, Kathleen M; Grammer, Geoffrey G

    2014-11-01

    Brugada syndrome (BrS) is a common occult cause of sudden cardiac arrest in otherwise healthy-appearing adults. The pathognomonic electrocardiographic pattern may be unmasked only by certain medications, many of which are unknown. We report a case of a depressed but otherwise healthy man with an asymptomatic right bundle branch block on electrocardiography who experienced antidepressant-induced BrS and ultimately recovered with transcranial magnetic stimulation (TMS). After an initial trial of nortriptyline, the patient's depressive symptoms improved; however, he experienced a syncopal event and was subsequently diagnosed as having BrS. Cross titration to bupropion, which had not previously been known to exacerbate BrS, was followed by another cardiac event. As a result, the patient was referred for TMS as a substitute for pharmacotherapy. After 31 TMS sessions over 8 weeks, the patient demonstrated significant improvement by subjective report and objective reduction in his Patient Health Questionnaire-9 scores from 10 (moderate) to 1 (minimal). Transcranial magnetic stimulation is a Food and Drug Administration-approved nonpharmacologic treatment for depression. Given the potential lethality of BrS with known and unknown psychopharmacologic agents, providers should consider TMS as first-line therapy in this patient population. Bupropion should be added to the list of agents known to exacerbate this disease. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  7. Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice.

    Science.gov (United States)

    Szopa, Aleksandra; Poleszak, Ewa; Wyska, Elżbieta; Serefko, Anna; Wośko, Sylwia; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr

    2016-02-01

    Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals' behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in

  8. A review on antidepressant effect of medicinal plants

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2017-03-01

    Full Text Available Depression is a life-threatening, debilitating, and common disease affecting different segments of community. Chemical and synthetic drugs available to treat this disease cause many adverse effects and may lead to complete recovery in only 50% of patients. At the same time, medicinal plants have been reported to exert optimal pharmacological effects in treating depression in different models. In this review, the relevant articles indexed in the reliable databases PubMed, PubMed central, Scopus and Web of Science were review-ed. The review indicated that most medicinal plants exerted antidepressant effects through synaptic regulation of serotonin, noradrenaline, and dopamine, regulating activity of hypothalamic-pituitary-adrenal axis, reinfor-cing anti-oxidant defense system, and decreasing inflammatory mediators. The medicinal plants and their active compounds can relieve depression through different pathways and hence are considered a new source to produce antidepressants.

  9. Neurofibromin Modulates Adult Hippocampal Neurogenesis and Behavioral Effects of Antidepressants

    Science.gov (United States)

    Li, Yun; Li, Yanjiao; McKay, Renée M.; Riethmacher, Dieter; Parada, Luis F.

    2012-01-01

    Neurogenesis persists in the rodent dentate gyrus (DG) throughout adulthood but declines with age and stress. Neural progenitor cells (NPCs) residing in the subgranular zone of the DG are regulated by an array of growth factors and respond to the microenvironment, adjusting their proliferation level to determine the rate of neurogenesis. Here we report that genetic deletion of neurofibromin (Nf1), a tumor suppressor with RAS-GAP activity,in adult NPCs enhanced DG proliferation and increased generation of new neurons in mice. Nf1 loss-associated neurogenesis had the functional effect of enhancing behavioral responses to subchronic antidepressants and, over time, led to spontaneous antidepressive-like behaviors. Thus, our findings establish an important role for the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate that activation of adult NPCs is sufficient to modulate depression- and anxiety-like behaviors. PMID:22399775

  10. Radioimmunoassay for nortriptyline (and other tricyclic antidepressants) in plasma

    International Nuclear Information System (INIS)

    Maguire, K.P.; Burrows, G.D.; Norman, T.R.; Scoggins, B.A.

    1978-01-01

    The radioimmunoassay for nortriptyline described here can detect as little 1 μg/liter of plasma. Within-day precision and day-to-day precision (CV) were +-6 and +-11%, respectively, over the concentration range 100 to 200 μg/liter. The major metabolite hydroxy-nortriptyline does not cross react with the antiserum. Results so obtained correlate closely with results by a double-isotope derivative dilution technique. The major advantages of this technique over currently available methods are its sensitivity, convenience (many samples can be processed in one day), simplicity, and cost. Further, prior extraction of plasma samples is not required. Cross-reactivity studies have been carried out with all other available tricyclic antidepressants. The antiserum has the ability to bind these drugs, thus radioimmunoassay for all the tricyclic antidepressant drugs can be set up because concurrent use of more than one of these drugs is rare

  11. Parasomnias and Antidepressant Therapy: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Lara eKierlin

    2011-12-01

    Full Text Available There exists a varying level of evidence linking the use of antidepressant medication to the parasomnias, ranging from larger, more comprehensive studies in the area of RBD to primarily case reports in the NREM parasomnias. As such, practice guidelines are lacking regarding specific direction to the clinician who may be faced with a patient who has developed a parasomnia that appears to be temporally related to use of an antidepressant. In general, knowledge of the mechanisms of action of the medications, particularly with regard to the impact on sleep architecture, can provide some guidance. There is a potential for SSRIs, TCAs, and SNRIs to suppress REM, as well as the anticholinergic properties of the individual drugs to further disturb normal sleep architecture.

  12. MAPK signaling correlates with the antidepressant effects of ketamine.

    Science.gov (United States)

    Réus, Gislaine Z; Vieira, Flavio Geraldo; Abelaira, Helena M; Michels, Monique; Tomaz, Débora B; dos Santos, Maria Augusta B; Carlessi, Anelise S; Neotti, Morgana V; Matias, Beatriz I; Luz, Jaíne R; Dal-Pizzol, Felipe; Quevedo, João

    2014-08-01

    Studies have pointed to a relationship between MAPK kinase (MEK) signaling and the behavioral effects of antidepressant drugs. So, in the present study we examined the behavioral and molecular effects of ketamine, an antagonist of the N-methyl-d-aspartate receptor (NMDA), which has been shown to have an antidepressant effect after the inhibition of MEK signaling in Wistar rats. Our results showed that acute administration of the MEK inhibitor PD184161, produced depressive-like behavior and stopped antidepressant-like effects of ketamine in the forced swimming test. The phosphorylation of extracellular signal-regulated kinase 1/2 (pERK 1/2) was decreased by PD184161 in the amygdala and nucleus accumbens, and the effects of ketamine on pERK 1/2 in the prefrontal cortex and hippocampus were inhibited by PD184161. The ERK 2 levels were decreased by PD184161 in the nucleus accumbens; and the effects of ketamine were blocked in this brain area. The p38 protein kinase (p38MAPK) and proBDNF were inhibited by PD184161, and the MEK inhibitor prevented the effects of ketamine in the nucleus accumbens. In addition, ketamine increased pro-BDNF levels in the hippocampus. In conclusion, our findings demonstrated that an acute blockade of MAPK signaling lead to depressive-like behavior and stopped the antidepressant response of ketamine, suggesting that the effects of ketamine could be mediated, at least in part, by the regulation of MAPK signaling in these specific brain areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Contemporary approach to pharmacological and clinical aspects of novel antidepressants

    OpenAIRE

    Danilevičiūtė, Vita; Sveikata, Audrius

    2002-01-01

    Depression is the most common illness that affects a large number of individuals in all countries. Recent evidence suggest that depressive episodes if left untreated may heighten severity of subsequent episodes and may increase need for more health care resources. The first antidepressants, tricyclics and monoamine oxidase inhibitors, became available in the late 1950s. A progressive tightening of requirements by drug licensing authorities has ensured that efficacy evidence is good for most a...

  14. Psychosocial work environment and antidepressant medication: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Westergaard-Nielsen Niels

    2009-07-01

    Full Text Available Abstract Background Adverse psychosocial work environments may lead to impaired mental health, but it is still a matter of conjecture if demonstrated associations are causal or biased. We aimed at verifying whether poor psychosocial working climate is related to increase of redeemed subscription of antidepressant medication. Methods Information on all antidepressant drugs (AD purchased at pharmacies from 1995 through 2006 was obtained for a cohort of 21,129 Danish public service workers that participated in work climate surveys carried out during the period 2002–2005. Individual self-reports of psychosocial factors at work including satisfaction with the work climate and dimensions of the job strain model were obtained by self-administered questionnaires (response rate 77,2%. Each employee was assigned the average score value for all employees at his/her managerial work unit [1094 units with an average of 18 employees (range 3–120]. The risk of first-time AD prescription during follow-up was examined according to level of satisfaction and psychosocial strain by Cox regression with adjustment for gender, age, marital status, occupational status and calendar year of the survey. Results The proportion of employees that received at least one prescription of ADs from 1995 through 2006 was 11.9% and prescriptions rose steadily from 1.50% in 1996 to the highest level 6.47% in 2006. ADs were prescribed more frequent among women, middle aged, employees with low occupational status and those living alone. None of the measured psychosocial work environment factors were consistently related to prescription of antidepressant drugs during the follow-up period. Conclusion The study does not indicate that a poor psychosocial work environment among public service employees is related to prescription of antidepressant pharmaceuticals. These findings need cautious interpretation because of lacking individual exposure assessments.

  15. Identification of a novel, fast-acting GABAergic antidepressant.

    Science.gov (United States)

    McMurray, K M J; Ramaker, M J; Barkley-Levenson, A M; Sidhu, P S; Elkin, P K; Reddy, M K; Guthrie, M L; Cook, J M; Rawal, V H; Arnold, L A; Dulawa, S C; Palmer, A A

    2018-02-01

    Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST). We also examined the effects of GLO1 inhibition in three models of antidepressant onset: the chronic FST (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy (OBX). Genetic knockdown of Glo1 or pharmacological inhibition using two structurally distinct GLO1 inhibitors (S-bromobenzylglutathione cyclopentyl diester (pBBG) or methyl-gerfelin (MeGFN)) reduced immobility in the TST and acute FST. Both GLO1 inhibitors also reduced immobility in the cFST after 5 days of treatment. In contrast, the serotonin reuptake inhibitor fluoxetine (FLX) reduced immobility after 14, but not 5 days of treatment. Furthermore, 5 days of treatment with either GLO1 inhibitor blocked the depression-like effects induced by CMS on the FST and coat state, and attenuated OBX-induced locomotor hyperactivity. Finally, 5 days of treatment with a GLO1 inhibitor (pBBG), but not FLX, induced molecular markers of the antidepressant response including brain-derived neurotrophic factor (BDNF) induction and increased phosphorylated cyclic-AMP response-binding protein (pCREB) to CREB ratio in the hippocampus and medial prefrontal cortex (mPFC). Our findings indicate that GLO1 inhibitors may provide a novel and fast-acting pharmacotherapy for depression.

  16. Identification of a novel, fast acting GABAergic anti-depressant

    Science.gov (United States)

    McMurray, Katherine M. J.; Ramaker, Marcia J.; Barkley-Levenson, Amanda M.; Sidhu, Preetpal S.; Elkin, Pavel; Reddy, M. Kashi; Guthrie, Margaret L.; Cook, James M.; Rawal, Viresh H.; Arnold, Leggy A.; Dulawa, Stephanie C.; Palmer, Abraham A.

    2017-01-01

    Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST). We also examined the effects of GLO1 inhibition in three models of antidepressant onset: the chronic FST (cFST), chronic mild stress (CMS) paradigm, and olfactory bulbectomy (OBX). Genetic knockdown of Glo1 or pharmacological inhibition using two structurally distinct GLO1 inhibitors (S-bromobenzylglutathione cyclopentyl diester (pBBG) or methyl gerfelin (MeGFN)) reduced immobility in the TST and acute FST. Both GLO1 inhibitors also reduced immobility in the cFST after 5 days of treatment. In contrast, the serotonin reuptake inhibitor fluoxetine (FLX) reduced immobility after 14, but not 5 days of treatment. Furthermore, 5 days of treatment with either GLO1 inhibitor blocked the depression-like effects induced by CMS on the FST and coat state, and attenuated OBX-induced locomotor hyperactivity. Finally, 5 days of treatment with a GLO1 inhibitor (pBBG), but not FLX, induced molecular markers of the antidepressant response including brain-derived neurotrophic factor (BDNF) induction and increased phosphorylated cyclic-AMP response binding protein (pCREB) to CREB ratio in the hippocampus and medial prefrontal cortex (mPFC). Our findings indicate that GLO1 inhibitors may provide a novel and fast-acting pharmacotherapy for depression. PMID:28322281

  17. Blonanserin - A Novel Antianxiety and Antidepressant Drug? An Experimental Study.

    Science.gov (United States)

    Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

    2016-09-01

    Many psychiatric disorders show signs and symptoms of anxiety and depression. A drug with both, effects and lesser adverse effects is always desired. Blonanserin is a novel drug with postulated effect on anxiety and depression. The study was aimed to evaluate the effect of Blonanserin on anxiety and depression in animal models. By using elevated plus maze test and forced swimming test, the antianxiety and antidepressant effects were evaluated. Animal ethics protocols were followed strictly. Total 50 rats (10 rats per group) were used for each test. As a control drug diazepam and imipramine were used in elevated plus maze and forced swimming test respectively. Blonanserin was tested for 3 doses 0.075, 0.2 and 0.8mg. These doses were selected from previous references as well as by extrapolating human doses. This study showed an antianxiety effect of Blonanserin comparable to diazepam, which was statistically significant. Optimal effect was observed with 0.075mg, followed by 0.2 and 0.8mg. It also showed an antidepressant effect which was statistically significant. Optimal effect was observed at 0.2mg dose. The results showed that at a dose range of 0.075 and 0.2mg Blonanserin has potential to exert an adjuvant antianxiety and antidepressant activity in animal models. In order to extrapolate this in patient, longer clinical studies with comparable doses should be planned. The present study underlines potential of Blonanserin as a novel drug for such studies.

  18. Pediatric antidepressant medication errors in a national error reporting database.

    Science.gov (United States)

    Rinke, Michael L; Bundy, David G; Shore, Andrew D; Colantuoni, Elizabeth; Morlock, Laura L; Miller, Marlene R

    2010-01-01

    To describe inpatient and outpatient pediatric antidepressant medication errors. We analyzed all error reports from the United States Pharmacopeia MEDMARX database, from 2003 to 2006, involving antidepressant medications and patients younger than 18 years. Of the 451 error reports identified, 95% reached the patient, 6.4% reached the patient and necessitated increased monitoring and/or treatment, and 77% involved medications being used off label. Thirty-three percent of errors cited administering as the macrolevel cause of the error, 30% cited dispensing, 28% cited transcribing, and 7.9% cited prescribing. The most commonly cited medications were sertraline (20%), bupropion (19%), fluoxetine (15%), and trazodone (11%). We found no statistically significant association between medication and reported patient harm; harmful errors involved significantly more administering errors (59% vs 32%, p = .023), errors occurring in inpatient care (93% vs 68%, p = .012) and extra doses of medication (31% vs 10%, p = .025) compared with nonharmful errors. Outpatient errors involved significantly more dispensing errors (p errors due to inaccurate or omitted transcription (p errors. Family notification of medication errors was reported in only 12% of errors. Pediatric antidepressant errors often reach patients, frequently involve off-label use of medications, and occur with varying severity and type depending on location and type of medication prescribed. Education and research should be directed toward prompt medication error disclosure and targeted error reduction strategies for specific medication types and settings.

  19. Serotonergic antidepressants as predictors of depressive disorders treatment

    Directory of Open Access Journals (Sweden)

    Timotijević Ivana P.

    2014-01-01

    Full Text Available From Kraepelin time to these days, biochemical, neurophysiological and neuropsychological complexity of depression has been reviewed in many different ways, but SSRI antidepressants have unquestionably brought about a significant drift in comprehension of disease, recognition of symptoms, and management. The fact is that high tech and accurate molecular studies may differentiate biological basis (receptor activity, transmitter concentrations not only in synapses, but also in particular CNS structures, cascade processes to changes of genomes in postsynaptic neurons of some depression symptoms. It is a significant progress in overview of psychiatric disorders because any symptom has its equivalent in CNS processes as antidepressants have their recognizable mechanisms of action. In this dynamic drug/disease relation, standard psychiatric classifications maintain their significance yet their approach remains descriptive what is no longer enough for selection of psychopharmacotherapy. Abandonment of categorical and adoption of dimensional approach means that any individual patient has his individual symptom portfolio created and that every symptom is hypothetically mapped in appropriate CNS structures and corresponding impaired information processes, dependent upon neurotransmitter pathways within these structures and connecting neuronal networks. Such approach opens up a possibility for combination of psychopharmacological drugs in different psychiatric categories what will be a huge benefit for patients, because targeted psychopharmacotherapy adjusts therapeutical effect and reduces the number of side effects and intolerable interactions. SSRI antidepressants, due to their broad spectrum of pharmacological characteristics and multiple psychiatric indications may be predictors of diagnostic categorization, causal psychopharmacotherapy and path to further research of etiopathogenesis of affective disorders.

  20. Antidepressant Use Amongst College Students: Findings of a Phenomenological Study

    Directory of Open Access Journals (Sweden)

    Reshmi L. Singh, Ph.D

    2012-01-01

    Full Text Available Background: Depression among college students is an escalating problem and could have serious consequences such as suicide. There has been an increase in use of antidepressants on college campuses in United States. However, an in depth understanding of this phenomenon from the college student’s perspective is lacking in the literature. Objective: This study examined college students’ experiences and treatment decision making during their depression treatment. Methods: A longitudinal, phenomenological research methodology was completed. The participants were nine students who were taking antidepressants for diagnosis of depression. Recruitment was done via brochures placed at University bulletin boards, and a mental health clinic. Three audio taped, unstructured interviews were conducted with each participant over four months. The central question asked was: What has the experience of treating depression been for you? Analysis of text was done using Van Manen’s lifeworld existentials of lived body, lived time, lived relation and lived space as the organizing framework. Results: Thirteen themes were identified within the four lifeworlds. The results showed that lived relation with providers was important for college students’ decision to both initiate and continue antidepressant use. Students’ role was defined in conjunction with provider’s role by them as wanting to be a ‘player’ in their treatment decisions and needing to be ‘acknowledged’ as such by their providers. Conclusions: Overall, the underlying essential theme of ‘autonomy’ was portrayed by the students’ experiential accounts of their depression treatment and treatment decision making.

  1. Antidepressant Use Amongst College Students: Findings of a Phenomenological Study

    Directory of Open Access Journals (Sweden)

    Reshmi L. Singh

    2012-01-01

    Full Text Available Background: Depression among college students is an escalating problem and could have serious consequences such as suicide. There has been an increase in use of antidepressants on college campuses in United States. However, an in depth understanding of this phenomenon from the college student's perspective is lacking in the literature. Objective: This study examined college students' experiences and treatment decision making during their depression treatment. Methods: A longitudinal, phenomenological research methodology was completed. The participants were nine students who were taking antidepressants for diagnosis of depression. Recruitment was done via brochures placed at University bulletin boards, and a mental health clinic. Three audio taped, unstructured interviews were conducted with each participant over four months. The central question asked was: What has the experience of treating depression been for you? Analysis of text was done using Van Manen's lifeworld existentials of lived body, lived time, lived relation and lived space as the organizing framework. Results: Thirteen themes were identified within the four lifeworlds. The results showed that lived relation with providers was important for college students' decision to both initiate and continue antidepressant use. Students' role was defined in conjunction with provider's role by them as wanting to be a 'player' in their treatment decisions and needing to be 'acknowledged' as such by their providers. Conclusions: Overall, the underlying essential theme of ‘autonomy’ was portrayed by the students’ experiential accounts of their depression treatment and treatment decision making.   Type: Original Research

  2. Accelerated antidepressant response to lithium augmentation of imipramine

    Directory of Open Access Journals (Sweden)

    Rajiv Saini

    2016-01-01

    Full Text Available Background: Treatment of depressive episode often poses a challenge. Although there are numerous medicines available for its treatment but they all have a lag period of 2–3 weeks before they start showing their result. Aim: The aim of the present study was to test the hypothesis that an initial lithium-tricyclic antidepressant (TCA combination has a quicker and better antidepressant effect than standard TCA treatment in unipolar depression. Materials and Methods: Twenty unipolar depressed inpatients under lithium-TCA treatment were compared with twenty patients with similar diagnosis treated with TCA-placebo combination. The duration of the study was 4 weeks under double-blind conditions. Results: Initial lithium-TCA treatment reduced depressive symptoms significantly more than TCA alone. The difference was evident from 1st week onward and persisted at 4 weeks. Conclusion: Lithium augmentation of TCA at the outset offers a strategy to reduce the lag period of antidepressant action. The choice can be made for those patients who are likely to benefit from long-term prophylaxis.

  3. Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression

    Science.gov (United States)

    Lener, Marc S.; Kadriu, Bashkim; Zarate, Carlos A.

    2017-01-01

    Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder (MDD) and bipolar depression. In clinical studies of individuals with MDD and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants. This review will highlight the evidence supporting the antidepressant effects of subanesthetic-dose ketamine as well as other glutamatergic modulators, such as D-cycloserine (DCS), riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide (N2O), GLYX-13, and esketamine. PMID:28194724

  4. Agmatine enhances the antidepressant-like effect of lithium in mouse forced swimming test through NMDA pathway.

    Science.gov (United States)

    Mohseni, Gholmreza; Ostadhadi, Sattar; Imran-Khan, Muhammad; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Haddadi, Nazgol-Sadat; Dehpour, Ahmad-Reza

    2017-04-01

    Depression is one the world leading global burdens leading to various comorbidities. Lithium as a mainstay in the treatment of depression is still considered gold standard treatment. Similar to lithium another agent agmatine has also central protective role against depression. Since, both agmatine and lithium modulate various effects through interaction with NMDA receptor, therefore, in current study we aimed to investigate the synergistic antidepressant-like effect of agmatine with lithium in mouse force swimming test. Also to know whether if such effect is due to interaction with NMDA receptor. In our present study we found that when potent dose of lithium (30mg/kg) was administered, it significantly decreased the immobility time. Also, when subeffective dose of agmatine (0.01mg/kg) was coadministered with subeffective dose of lithium (3mg/kg), it potentiated the antidepressant-like effect of subeffective dose of lithium. For the involvement of NMDA receptor in such effect, we administered NMDA receptor antagonist MK-801 (0.05mg/kg) with a combination of subeffective dose of lithium (3mg/kg) and agmatine (0.001mg/kg). A significant antidepressant-like effect was observed. Furthermore, when subeffective dose (50 and 75mg/kg) of NMDA was given it inhibited the synergistic effect of agmatine (0.01mg/kg) with lithium (3mg/kg). Hence, our finding demonstrate that agmatine have synergistic effect with lithium which is mediated by NMDA receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Antidepressant Use and Risk of Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Weeke, P; Jensen, Aksel Karl Georg; Folke, F

    2012-01-01

    being the most frequently used type of antidepressant (50.8%). Tricyclic antidepressants (TCAs; odds ratio (OR) = 1.69, confidence interval (CI): 1.14-2.50) and selective serotonin reuptake inhibitors (SSRIs; OR = 1.21, CI: 1.00-1.47) were both associated with comparable increases in risk of OHCA.......17-12.2). An association between cardiac arrest and antidepressant use could be documented in both the SSRI and TCA classes of drugs....

  6. Economic Effects of Anti-Depressant Usage on Elective Lumbar Fusion Surgery

    Directory of Open Access Journals (Sweden)

    Amirali Sayadipour

    2016-07-01

    Full Text Available Background: It has been suggested, although not proven, that presence of concomitant psychiatric disorders may increase the inpatient costs for patients undergoing elective surgery. This study was designed to test the hypothesis that elective lumbar fusion surgery is more costly in patients with under treatment for depression. Methods: This is a retrospective case-control study of 142 patients who underwent elective lumbar fusion. Of those 142 patients, 41 patients were chronically using an antidepressant medication that considered as a "study group", and 101 patients were not taking an antidepressant medication that considered as a "control group". Data was collected for this cohort regarding antidepressant usage patient demographics, length of stay (LOS, age-adjusted Charlson comorbidity index scores and cost. Costs were compared between those with a concomitant antidepressant usage and those without antidepressant usage using multivariate analysis. Results: Patients using antidepressants and those with no history of antidepressant usage were similar in terms of gender, age and number of operative levels. The LOS demonstrated a non-significant trend towards longer stays in those using anti-depressants. Total charges, payments, variable costs and fixed costs were all higher in the antidepressant group but none of the differences reached statistical significance. Using Total Charges as the dependent variable, gender and having psychiatric comorbidities were retained independent variables. Use of an antidepressant was independently predictive of a 36% increase in Total Charges . Antidepressant usage as an independent variable also conferred a 22% increase in cost and predictive of a 19% increase in Fixed Cost . Male gender was predictive of a 30% increase in Total Charges . Conclusion: This study suggests use of antidepressant in patients who undergo elective spine fusion compared with control group is associated with increasing total cost and

  7. The Strategy of Combining Antidepressants in the Treatment of Major Depression: Clinical Experience in Spanish Outpatients

    OpenAIRE

    Luis M. Martín-López; Jose E. Rojo; Karina Gibert; Juan Carlos Martín; Lyli Sperry; Lurdes Duñó; Antonio Bulbena; Julio Vallejo

    2011-01-01

    Introduction. The combination of antidepressants is a useful tool in the treatment of major depression, especially in cases where there is a partial response to antidepressant monotherapy. However, the use of this strategy is a matter of controversy, and its frequency of use in clinical practice is not clear. The aim of our study is to assess the use of antidepressants combination in Spain by reviewing three databases used between 1997 and 2001. Methods. Databases pertain to patien...

  8. Differential Risk of Peptic Ulcer Among Users of Antidepressants Combined With Nonsteroidal Anti-inflammatory Drugs.

    Science.gov (United States)

    Shin, Ju-Young; Song, Inmyung; Lee, Jin-Ho; Yoon, Jong Lull; Kwon, Jun Soo; Park, Byung-Joo

    2017-04-01

    Selective serotonin reuptake inhibitors (SSRIs) have been reported to have an increased risk of gastrointestinal adverse events, and the risk may be further increased by combined use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, little has been known about the risk of peptic ulcer associated with other classes of antidepressants or individual antidepressants combined with NSAIDs. We conducted a retrospective cohort study to define the risk of peptic ulcer associated with combined use of antidepressants and NSAIDs, as compared with use of antidepressants alone. Using the Korean Health Insurance Review and Assessment Service database, we identified a total of 1,127,622 patients who began receiving antidepressants between 2009 and 2012. Propensity-based matching and Cox proportional hazards models were used to compare the risk of peptic ulcer between antidepressant users with NSAIDs and those without NSAIDs matched in a 1:1 ratio, for a total of 768,850 patients. The risk of peptic ulcer did not increase with combined use of overall antidepressants and NSAIDs, as compared with antidepressant use alone (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.99-1.06). A slightly increased risk was observed for combined use of NSAIDs with tricyclic antidepressants (HR, 1.15; 95% CI, 1.09-1.21) and with SSRIs (HR, 1.08; 95% CI, 1.01-1.16). We found that although concomitant use of NSAIDs and antidepressants was not associated with an increased risk of peptic ulcer for antidepressants in general, it was so for some specific classes including tricyclic antidepressants and SSRIs. However, we cannot rule out the possibility that the increased risk was solely due to NSAID use.

  9. Depression, antidepressant medications, and risk of Clostridium difficile infection

    Science.gov (United States)

    2013-01-01

    Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI. PMID:23647647

  10. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  11. [Evolution in consumption of anti-depressants during the years 2002 to 2004].

    Science.gov (United States)

    Serna Arnáiz, Catalina; Galván Santiago, Leonardo; Gascó Eguíluz, Eduardo; Santafé Soler, Plácido; Martín Gracia, Elisabeth; Vila Parrot, Teresa

    2006-11-15

    To analyse the use of antidepressants from 2002 to 2004 and the length of treatment. Cross-sectional, descriptive study of antidepressant drugs prescribed through the National Health System during 2002-2004. Lleida Health Region, Spain. A total of 54,890 patients received an antidepressant drug between 2002 and 2004. Age, sex, medicine, prescription period, centre. The prevalence of antidepressant treatment was: 8.4% in 2002 (368,976 inhabitants); 8.6% in 2003 (376,638 inhabitants); and 8.7% in 2004 (388,148 inhabitants). The increase in antidepressant treatment in 2004 over 2002 was 9.4%. Prevalence among men was 5.4% and women, 12.7%. The distribution according to antidepressant classes was: selective serotonin reuptake inhibitors, 73.7%; tricyclic antidepressants, 26.2%; heterocyclic antidepressants, 10%, and monoamine oxidase inhibitors, 0.1%. The duration of treatment was 1 to 3 months (43%), 4 to 12 months (22.7%), 13 to 24 months (14.4%), and over 24 months (19.9%). A steady increase in the use of antidepressants is being observed, predominantly new drugs. Regarding the length of treatment, a high proportion of patients are treated for under 4 months, which does not follow recent recommendations in the scientific literature for treatment of depression. This is a major element of inefficiency in the health system.

  12. Differential role of AMPA receptors in mouse tests of antidepressant and anxiolytic action

    DEFF Research Database (Denmark)

    Andreasen, Jesper T; Fitzpatrick, Ciaran M; Larsen, Maria

    2015-01-01

    Depression and anxiety often co-occur, and conventional monoamine-facilitating antidepressants show efficacy against symptoms in both disorders. Rodent studies indicate that antidepressant effects of monoamine-based antidepressants involve increased α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic...... a depressogenic-like effect in the TST but no effect in the FST. Conversely, GYKI-53655 produced marked anxiolytic-like effects in the EZM (≥ 2.5 mg/kg), MBT (≥ 2.5 mg/kg), and NIH tests (≥ 5 mg/kg), while LY451646 (≥ 3 mg/kg) increased anxiety-like behaviour in the EZM. Citalopram showed an antidepressant...

  13. Effects of antidepressant drugs on histamine-H1 receptors in the brain

    International Nuclear Information System (INIS)

    Hall, H.; Oegren, S.O.

    1984-01-01

    The histamine-H 1 receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a 3 H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H 1 receptor. Some newer antidepressant drugs, such as zimeldine and nomifensine were devoid of activity while others, such as iprindole and mianserin were very potent. It is concluded that antagonistic effects on the histamine-H 1 receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs

  14. Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

    Science.gov (United States)

    McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Arndt, Katlyn; Erickson, Maia; Tabatabai, Grace; Boeve, Bradley F; Silber, Michael H

    2015-06-01

    REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Tertiary-care sleep center. Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. N/A. RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD. © 2015 Associated Professional Sleep Societies, LLC.

  15. Murine depression model and its potential applications for discovering foods and farm products with antidepressant-like effects

    Directory of Open Access Journals (Sweden)

    Tatsuhiko eGoto

    2016-03-01

    Full Text Available Advanced societies face increased health problems related to various stresses. Chronic psychological stress is a major risk factor for psychiatric disorders such as depression. Although therapeutic agents reduce several symptoms of depression, most have side effects in a broad range of the population. Furthermore, some victims of depression do not show significant improvement with any drugs, so alternative approaches are needed. Good dietary habits may potentially reduce depressive symptoms, but there is little scientific evidence thus far. Murine depression models are useful to test nutritional approaches in vivo. Our model mice subjected to a subchronic mild social defeat stress (sCSDS paradigm show several alterations in physiological parameters and social behavior. These stress-induced symptoms in sCSDS mice can be used as cues to identify antidepressant-like natural resources including foods and farm products. We previously discovered that sCSDS mice show more vulnerability to social stress by changing dietary condition. In addition, we developed a more objective system for analyzing mouse behavior using a 3D depth-sensing camera to understand relationships between diet and behavior. The combination of sCSDS mice with 3D behavioral analysis is a powerful method for screening ingredients in foods and farm products for antidepressant-like effects.

  16. Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants.

    Science.gov (United States)

    Gore, Mugdha; Tai, Kei-Sing; Chandran, Arthi; Zlateva, Gergana; Leslie, Douglas

    2012-01-01

    To examine treatment patterns and costs among patients with fibromyalgia prescribed pregabalin or tricyclic antidepressants (TCAs). Using the LifeLink™ Health Plan Claims Database, patients with fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed (index date) TCAs (n = 898) were identified and propensity score-matched (PSM) with patients newly prescribed pregabalin (n = 898). Pain-related pharmacotherapy, comorbidities, and healthcare resource use/costs were examined during the 12 months, pre-index, and follow-up periods. Both patient groups reported multiple comorbidities and received pain medications in the pre-index and follow-up periods. Among patients prescribed pregabalin, use of non-selective non-steroidal anti-inflammatory drugs (43.3% vs 39.8%), other anticonvulsants (28.6% vs 23.3%), and tetracyclic/miscellaneous antidepressants (28.5% vs 25.8%) significantly decreased, and cyclooxygenase 2 (COX-2) inhibitors (7.7% vs 10.4%), TCAs (4.8% vs 7.9%), and topical agents (10.8% vs 15.1%) increased in the follow-up period (p fibromyalgia to pregabalin. Patients with fibromyalgia prescribed pregabalin or TCAs had multiple comorbidities and a sizeable pain medication burden, which increased in the follow-up period for both cohorts. Only 5% of pregabalin initiators had been treated with concomitant TCAs at baseline, suggesting that TCAs were inappropriate for these patients owing to their contraindications.

  17. Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment.

    Science.gov (United States)

    Farahani, Arusha; Correll, Christoph U

    2012-04-01

    To perform a meta-analysis of antidepressant-antipsychotic cotreatment versus antidepressant or antipsychotic monotherapy for psychotic depression. We performed an electronic search (from inception of databases until February 28, 2011) in PubMed/MEDLINE, Cochrane Library, and PsycINFO, without language or time restrictions. Search terms were (psychosis OR psychotic OR hallucinations OR hallucinating OR delusions OR delusional) AND (depression OR depressed OR major depressive disorder) AND (random OR randomized OR randomly). Eight randomized, placebo-controlled acute-phase studies in adults (N = 762) with standardized criteria-defined psychotic depression (including Research Diagnostic Criteria, DSM-III, DSM-IV, or ICD-10) were meta-analyzed, yielding 10 comparisons. Antidepressant-antipsychotic cotreatment was compared in 5 trials with 6 treatment arms (n = 337) with antidepressant monotherapy and in 4 trials with 4 treatment arms (n = 447) with antipsychotic monotherapy. Primary outcome was study-defined inefficacy; secondary outcomes included all-cause discontinuation, specific psychopathology ratings, and side effects. Using random effects models, we calculated relative risk (RR) with 95% confidence intervals (CIs), number-needed-to-treat/harm (NNT/NNH), and effect size (ES). Antidepressant-antipsychotic cotreatment outperformed antidepressant monotherapy regarding less study-defined inefficacy (no. of comparisons = 6; n = 378; RR = 0.76; 95% CI, 0.59-0.98; P = .03; heterogeneity [I2] = 34%) (NNT = 7; 95% CI, 4-20; P = .009) and Clinical Global Impressions-Severity of Illness scores (no. of comparisons = 4; n = 289; ES = -0.25; 95% CI, -0.49 to -0.02; P = .03; I2 = 0%), with trend-level superiority for depression ratings (no. of comparisons = 5; n = 324; ES = -0.20; 95% CI, -0.44 to 0.03; P = .09; I2 = 10%), but not regarding psychosis ratings (no. of comparisons = 3; n = 161; ES = -0.24; 95% CI, -0.85 to 0.38; P = .45; I2 = 70%). Antidepressant

  18. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  19. Reproductive hormones as psychotropic agents?

    African Journals Online (AJOL)

    QuickSilver

    receptors thus impairing antidepressant action which is re- stored by oestrogen. Serotonin receptors are desensitised in postmenopausal women; this is normalised with oestrogen supplementation. This may explain the synergy of oestrogen and antidepressants in some depressed women. Both oestro- reproductive.pm6.

  20. The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

    Science.gov (United States)

    Pacchiarotti, Isabella; Bond, David J.; Baldessarini, Ross J.; Nolen, Willem A.; Grunze, Heinz; Licht, Rasmus W.; Post, Robert M.; Berk, Michael; Goodwin, Guy M.; Sachs, Gary S.; Tondo, Leonardo; Findling, Robert L.; Youngstrom, Eric A.; Tohen, Mauricio; Undurraga, Juan; González-Pinto, Ana; Goldberg, Joseph F.; Yildiz, Ayşegül; Altshuler, Lori L.; Calabrese, Joseph R.; Mitchell, Philip B.; Thase, Michael E.; Koukopoulos, Athanasios; Colom, Francesc; Frye, Mark A.; Malhi, Gin S.; Fountoulakis, Konstantinos N.; Vázquez, Gustavo; Perlis, Roy H.; Ketter, Terence A.; Cassidy, Frederick; Akiskal, Hagop; Azorin, Jean-Michel; Valentí, Marc; Mazzei, Diego Hidalgo; Lafer, Beny; Kato, Tadafumi; Mazzarini, Lorenzo; Martínez-Aran, Anabel; Parker, Gordon; Souery, Daniel; Özerdem, Ayşegül; McElroy, Susan L.; Girardi, Paolo; Bauer, Michael; Yatham, Lakshmi N.; Zarate, Carlos A.; Nierenberg, Andrew A.; Birmaher, Boris; Kanba, Shigenobu; El-Mallakh, Rif S.; Serretti, Alessandro; Rihmer, Zoltan; Young, Allan H.; Kotzalidis, Georgios D.; MacQueen, Glenda M.; Bowden, Charles L.; Ghaemi, S. Nassir; Lopez-Jaramillo, Carlos; Rybakowski, Janusz; Ha, Kyooseob; Perugi, Giulio; Kasper, Siegfried; Amsterdam, Jay D.; Hirschfeld, Robert M.; Kapczinski, Flávio; Vieta, Eduard

    2014-01-01

    Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications

  1. Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2007-01-01

    Full Text Available Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine; two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

  2. [Consumption of antidepressants in Chile from 1992 to 2004].

    Science.gov (United States)

    Jirón, Marcela; Machado, Márcio; Ruiz, Inés

    2008-09-01

    Data from the Ministry of Health show that in Chile in 2004, 17% of the population had some form of depression, and mood disorders are the tenth cause of disability-adjusted life years (DALY) loss. To determine consumption of antidepressants (ADs) in Chile from 1992 to 2004. National sales data were obtained from the company IMS Health Chile and converted into defined daily doses (DDDs) per 1,000 inhabitants per day. Available ADs were classified in four pharmacological groups (i.e., serotonin-norepinephrine reuptake inhibitors, SNRLs; selective-serotonin reuptake inhibitors, SSRLs; tricyclic antidepressants, TCAs; and others). Total economic burden of ADs utilization and cost per DDDs were also calculated. Trends over time were analyzed using Pearson-R2. Total ADs consumption in Chile measured by DDDs per 1,000 inhabitants per day (DHD) increased linearly (y =0.901x + 1.9129; R2 =0.9296; p economic burden of ADs in Chile (total cost of DDDs consumed) increased from US$65.4 million in 2001 to US$74.6 million in 2004 (14% increase). Average cost per DDD of all AD increased linearly, however not significantly from US$ 0.94 in 2001 to US$ 1.04 in 2004 (y =0.0362x + 0.8784; R2 =0.7382; p =0,262). DDDs per 1,000 inhabitants per day increased linearly over 470% from 1992-2004. SSRLs were the most commonly consumed drugs in Chile. Future research should evaluate the cost-effectiveness of antidepressants in Chile, comparing the results with drug utilization, and determining if unnecessary expenditures have been paid out.

  3. Antidepressant phenelzine alters differentiation of cultured human and mouse preadipocytes.

    Science.gov (United States)

    Chiche, Françoise; Le Guillou, Morwenna; Chétrite, Gérard; Lasnier, Françoise; Dugail, Isabelle; Carpéné, Christian; Moldes, Marthe; Fève, Bruno

    2009-05-01

    Change in body weight is a frequent side effect of antidepressants and is considered to be mediated by central effects on food intake and energy expenditure. The antidepressant phenelzine (Nardil) potently inhibits both monoamine oxidase and semicarbazide-sensitive amine oxidase activities, two enzymes that are highly expressed in adipose tissue, raising the possibility that it could directly alter adipocyte biology. Treatment with this compound is rather associated with weight gain. The aim of this work was to examine the effects of phenelzine on differentiation and metabolism of cultured human and mouse preadipocytes and to characterize the mechanisms involved in these effects. In all preadipocyte models, phenelzine induced a time- and dose-dependent reduction in differentiation and triglyceride accumulation. Modulation of lipolysis or glucose transport was not involved in phenelzine action. This effect was supported by the reduced expression in the key adipogenic transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein-alpha, which was observed only at the highest drug concentrations (30-100 microM). The PPAR-gamma agonists thiazolidinediones did not reverse phenelzine effects. By contrast, the reduction in both cell triglycerides and sterol regulatory element-binding protein-1c (SREBP-1c) was detectable at lower phenelzine concentrations (1-10 microM). Phenelzine effect on triglyceride content was prevented by providing free fatty acids to the cells and was partially reversed by overexpression of a dominant-positive form of SREBP-1c, showing the privileged targeting of the lipogenic pathway. When considered together, these findings demonstrate that an antidepressant directly and potently inhibits adipocyte lipid storage and differentiation, which could contribute to psychotropic drug side effects on energy homeostasis.

  4. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test.

    Science.gov (United States)

    Ostadhadi, Sattar; Ahangari, Mohammad; Nikoui, Vahid; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Jazaeri, Farahnaz; Chamanara, Mohsen; Akbarian, Reyhaneh; Dehpour, Ahmad-Reza

    2016-08-01

    Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (PNMDA (75mg/kg), l-arginine (750mg/kg, a substrate for nitric oxide synthase [NOS]) or sildenafil (5mg/kg, a phosphodiesterase [PDE] 5 inhibitor) reversed the antidepressant-like effect of lamotrigine (10mg/kg) in the FST. Injection of l-nitroarginine methyl ester (l-NAME, 10mg/kg, a non-specific NOS inhibitor), 7-nitroindazole (30mg/kg, a neuronal NOS inhibitor), methylene blue (20mg/kg, an inhibitor of both NOS and soluble guanylate cyclase [sGC]), or MK-801 (0.05mg/kg), ketamine (1mg/kg), and magnesium sulfate (10mg/kg) as NMDA receptor antagonists in combination with a sub-effective dose of lamotrigine (5mg/kg) diminished the immobility time of animals in the FST compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the OFT. Based on our findings, it is suggested that the antidepressant-like effect of lamotrigine might mediated through inhibition of either NMDA receptors or NO-cGMP synthesis. Copyright © 2016. Published by Elsevier Masson SAS.

  5. Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer's disease.

    Science.gov (United States)

    Hritcu, Lucian; Noumedem, Jaurès A; Cioanca, Oana; Hancianu, Monica; Postu, Paula; Mihasan, Marius

    2015-03-29

    Piper nigrum L. (Piperaceae) is employed in traditional medicine of many countries as analgesic, antiinflammatory, anticonvulsant, antioxidant, antidepressant and cognitive-enhancing agent. This study was undertaken in order to evaluate the possible anxiolytic, antidepressant and antioxidant properties of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer's disease. The anxiolytic- and antidepressant-like effects of the methanolic extract were studied by means of in vivo (elevated plus-maze and forced swimming tests) approaches. Also, the antioxidant activity in the amygdala was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). Significant differences were determined by Tukey's post hoc test. F values for which p < 0.05 were regarded as statistically significant. Pearson's correlation coefficient and regression analysis were used in order to evaluate the connection between behavioral measures, the antioxidant defence and lipid peroxidation. The beta-amyloid (1-42)-treated rats exhibited the following: decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Administration of the methanolic extract significantly exhibited anxiolytic- and antidepressant-like effects and also antioxidant potential. Taken together, our results suggest that the methanolic extract ameliorates beta-amyloid (1-42)-induced anxiety and depression by attenuation of the oxidative stress in the rat amygdala.

  6. Are gender differences important for the clinical effects of antidepressants?

    DEFF Research Database (Denmark)

    Hildebrandt, Malene Grubbe; Steyerberg, Ewout Willem; Stage, Kurt Bjerregaard

    2003-01-01

    and multiple linear and logistic regression models were used for statistical evaluations. RESULTS: Both genders had similar remission rates (Hamilton depression scale score ...OBJECTIVE: Gender differences in antidepressant treatment response, side effects, dropout rates, and plasma concentrations were examined in patients with major and predominantly melancholic depression. METHOD: The study included a subgroup of 292 inpatients (96 men, 196 women) from three Danish....... The plasma concentrations of clomipramine were significantly higher for female than for male patients. No gender differences were found in posttreatment Hamilton depression scale scores, nor did the therapeutic effects of treatment depend on gender. Rates of dropout and side effects were similar for men...

  7. Genetic predictors of response to antidepressants in the GENDEP project

    DEFF Research Database (Denmark)

    Uher, Rudolf; Huezo-Diaz, Patricia; Perroud, Nader

    2009-01-01

    ) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1...... testing. A false discovery rate of 0.106 for the three strongest associations indicated that the multiple findings are unlikely to be false positives. The pattern of associations indicated a degree of specificity with variants in genes encoding proteins in serotonin signaling influencing response...... proportion of variance in response to antidepressants, indicating a need for a multivariate approach to prediction....

  8. Interaction of antidepressants with the serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Sørensen, Lena; Andersen, Jacob; Thomsen, Mette

    2012-01-01

    as treatment of depression and anxiety disorders or as psychostimulant drugs of abuse. Despite their clinical importance, the molecular mechanisms by which various types of antidepressant drugs bind and inhibit SERT and NET are still elusive for the majority of the inhibitors, including the molecular basis...... SERT/NET inhibitors belonging to different drug classes. Analysis of the resulting drug sensitivity profiles provides novel information on drug binding modes in hSERT and hNET and identifies specific S1 residues as important molecular determinants for inhibitor potency and hSERT/hNET selectivity....

  9. Maternal depression, antidepressant use in pregnancy and Apgar scores in infants

    DEFF Research Database (Denmark)

    Jensen, Hans Mørch; Grøn, Randi; Lidegaard, Øjvind

    2013-01-01

    Use of antidepressants during pregnancy has been associated with a low Apgar score in infants but a contribution from the underlying depressive disorder might influence this association.......Use of antidepressants during pregnancy has been associated with a low Apgar score in infants but a contribution from the underlying depressive disorder might influence this association....

  10. Possible role of more positive social behaviour in the clinical effect of antidepressant drugs

    NARCIS (Netherlands)

    Young, Simon N.; Moskowitz, Debbie S.; aan Het Rot, Marije

    Increasing serotonin decreases quarrelsome behaviours and enhances agreeable behaviours in humans. Antidepressants, even those whose primary action is not on serotonin, seem to increase serotonin function. We suggest that antidepressants act in part by effects on social behaviour, which leads to a

  11. Antidepressant prescribing patterns in the nursing home: second-generation issues revisited.

    Science.gov (United States)

    Shah, Shruti; Schoenbachler, Ben; Streim, Joel; Meeks, Suzanne

    2012-05-01

    The object of this study was to provide an updated evaluation of the quality of antidepressant management and prescribing patterns in nursing homes in the context of organizational and resident factors. Pearson correlation and chi-square analyses were conducted using information gathered from random nursing home charts. Nursing home facilities in and around the Louisville, KY, metropolitan area (n = 10). Chart reviews were randomly chosen for 20% of long term care resident records in participating homes (n = 209). Demographic information, documentation of depression diagnoses, and antidepressant prescribing patterns were evaluated using the Quality of Depression Management and Antidepressant Prescribing rating scale and information found in the Minimum Data Set 2.0. Of the sample, 59.8% was prescribed antidepressants at the time of the chart review; 205 chart reviews indicated the absence or presence of a depression diagnosis. For those with documented depression diagnoses (n = 126), nearly one-quarter were not prescribed antidepressants. Of 79 chart reviews indicating no depression diagnosis, nearly a third were receiving an antidepressant. Documentation related to changes in dosing, the presence or absence of side effects, or reasons for continuation were suboptimal. Discrepancy between antidepressant prescribing and the presence/absence of depression diagnoses continue to exist for nursing home residents. The quality of antidepressant documentation in nursing home charts continues to be inadequate. Future research should aim to explore possible solutions to these discrepancies and deficiencies in documentation. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  12. Antidepressants use in children and adolescents and the risk of suicide

    NARCIS (Netherlands)

    Wohlfarth, Tamar D.; van Zwieten, Barbara J.; Lekkerkerker, Frits J.; Gispen-de Wied, Christine C.; Ruis, Jerry R.; Elferink, Andre J. A.; Storosum, Jitschak G.

    2006-01-01

    Antidepressants use in paediatric patients has been linked with risk of suicidal behaviours. The aim of this paper, therefore, is to examine whether all antidepressants are associated with such risk. All 22 paediatric short-term placebo-controlled trials of SSRIs and NSRIs that were submitted to

  13. Computational Model of Antidepressant Response Heterogeneity as Multi-pathway Neuroadaptation

    Directory of Open Access Journals (Sweden)

    Mariam B. Camacho

    2017-12-01

    Full Text Available Current hypotheses cannot fully explain the clinically observed heterogeneity in antidepressant response. The therapeutic latency of antidepressants suggests that therapeutic outcomes are achieved not by the acute effects of the drugs, but rather by the homeostatic changes that occur as the brain adapts to their chronic administration. We present a computational model that represents the known interactions between the monoaminergic neurotransmitter-producing brain regions and associated non-monoaminergic neurotransmitter systems, and use the model to explore the possible ways in which the brain can homeostatically adjust to chronic antidepressant administration. The model also represents the neuron-specific neurotransmitter receptors that are known to adjust their strengths (expressions or sensitivities in response to chronic antidepressant administration, and neuroadaptation in the model occurs through sequential adjustments in these receptor strengths. The main result is that the model can reach similar levels of adaptation to chronic administration of the same antidepressant drug or combination along many different pathways, arriving correspondingly at many different receptor strength configurations, but not all of those adapted configurations are also associated with therapeutic elevations in monoamine levels. When expressed as the percentage of adapted configurations that are also associated with elevations in one or more of the monoamines, our modeling results largely agree with the percentage efficacy rates of antidepressants and antidepressant combinations observed in clinical trials. Our neuroadaptation model provides an explanation for the clinical reports of heterogeneous outcomes among patients chronically administered the same antidepressant drug regimen.

  14. Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

    Science.gov (United States)

    El-Alfy, Abir T; Ivey, Kelly; Robinson, Keisha; Ahmed, Safwat; Radwan, Mohamed; Slade, Desmond; Khan, Ikhlas; ElSohly, Mahmoud; Ross, Samir

    2010-06-01

    The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (pcannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis. Published by Elsevier Inc.

  15. Antidepressants and Youth Suicide in New York City, 1999-2002

    Science.gov (United States)

    Leon, Andrew C.; Marzuk, Peter M.; Tardiff, Kenneth; Bucciarelli, Angela; Piper, Tinka Markham; Galea, Sandro

    2006-01-01

    Objective: To determine the proportion of youth suicides in New York City from 1999 to 2002 in which antidepressants were detected at autopsy. Method: This is a medical examiner surveillance study of suicides in New York City among those younger than 18 years of age. The outcome measure is serum toxicology for antidepressants. Results: From 1999…

  16. Patients' perceptions and illness severity at start of antidepressant treatment in general practice

    NARCIS (Netherlands)

    Van Geffen, Erica C.G.; Heerdink, Eiebert R.; Hugtenburg, Jacqueline G.; Siero, Frans W.; Egberts, Antoine C.G.; Van Hulten, Rolf

    2010-01-01

    Objectives Patients' perceptions are important to consider when trying to understand why patients often do not follow prescriptions for antidepressant treatment. This study aimed to investigate the influence of patients' perceptions and illness severity at the start on antidepressant-medication-

  17. Signaling pathways regulating Homer1a expression : implications for antidepressant therapy

    NARCIS (Netherlands)

    Serchov, Tsvetan; Heumann, Rolf; van Calker, Dietrich; Biber, Knut

    Homer1a is upregulated by several different antidepressant measures, including non-pharmacological treatments, like sleep deprivation (SD) and electroconvulsive therapy (ECT) and antidepressant drugs, such as imipramine, fluoxetine and ketamine. Homer1a induction might thus be a crucial joint

  18. Antidepressant Utilization and Suicide in Europe : An Ecological Multi-National Study

    NARCIS (Netherlands)

    Gusmao, Ricardo; Quintao, Sonia; McDaid, David; Arensman, Ella; Van Audenhove, Chantal; Coffey, Claire; Vaernik, Airi; Vaernik, Peeter; Coyne, James; Hegerl, Ulrich

    2013-01-01

    Background: Research concerning the association between use of antidepressants and incidence of suicide has yielded inconsistent results and is the subject of considerable controversy. The first aim is to describe trends in the use of antidepressants and rates of suicide in Europe, adjusted for

  19. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action

    DEFF Research Database (Denmark)

    Lucas, Guillaume; Rymar, Vladimir V; Du, Jenny

    2007-01-01

    Current antidepressants are clinically effective only after several weeks of administration. Here, we show that serotonin(4) (5-HT(4)) agonists reduce immobility in the forced swimming test, displaying an antidepressant potential. Moreover, a 3 day regimen with such compounds modifies rat brain...

  20. Side effects of antidepressants during long-term use in a naturalistic setting

    NARCIS (Netherlands)

    Bet, Pierre M.; Hugtenburg, Jacqueline G.; Penninx, Brenda W. J. H.; Hoogendijk, Witte J. G.

    2013-01-01

    Side effects of antidepressants are usually underreported in clinical trials and large scale naturalistic studies are restricted to six months of use. We examined the prevalence and nature of patient-perceived side effects and their determinants during long-term antidepressant use in a naturalistic

  1. Trends in the use of antidepressants among older adults: Bambuí Project

    Directory of Open Access Journals (Sweden)

    Antônio Ignácio de Loyola Filho

    2014-12-01

    Full Text Available OBJECTIVE To analyze the trends and factors associated with the antidepressant use among older adults. METHODS This population-based study evaluated older adults in 1997 (n = 351, baseline and the survivors at the 15th follow-up year (n = 462, in 2012 among the aging cohort of Bambuí. The prevalence of antidepressant use was estimated, and the most commonly used antidepressants each year were identified. Prevalence ratios with 95% confidence intervals were estimated using Poisson regression with robust variance to investigate differences in the prevalence of use between 1997 and 2012. RESULTS The overall consumption of antidepressants (PR = 2.87, 95%CI 1.94;4.25 and of selective serotonin reuptake inhibitors (PR = 7.50, 95%CI 3.74;15.02 was significantly higher in 2012. However, no significant difference was observed in the use of tricyclic antidepressants between the two cohorts (PR = 0.89, 95%CI 0.49;1.62. In the 2012 cohort, antidepressant use was associated with females, increased age, increased income (≥ 4 minimum wages, self-assessment of health as reasonable, and attending ≥ 5 medical consultations in the last 12 months. CONCLUSIONS The increased consumption of antidepressants in the period due to increased use of selective serotonin reuptake inhibitors was consistent with results observed in international studies of different population groups and contexts. The positive correlation observed between antidepressant use and family income may be a warning of possible inequalities in access to mental health services.

  2. PHARMACOEPIDEMIOLOGICAL MONITORING OF ANTIDEPRESSANT USAGE IN PATIENTS WITH ANXIOUS AND DEPRESSIVE SYNDROMES IN INTERNAL MEDICINE

    Directory of Open Access Journals (Sweden)

    N. V. Ivanova

    2015-12-01

    Full Text Available Aim. To study antidepressant usage in treatment of anxious and depressive disorders in real internal medicine practice.Material and methods. Retrospective analysis of 290 charts of patients, which were observed in Pskov region hospital from 2004 to 2005 was held. All patients suffered from different internal diseases and were treated with antidepressants because of anxious and depressive concomitant disorders.Results. Arterial hypertension observed in 28% of patients, ischemic heart disease – in 20%, heart failure – in 14%, cerebrovascular and peripheral nervous system diseases – in 18% and gastroduodenal diseases – in 20% of patients. Amitriptyline took the first place (49% among antidepressant prescriptions. Next antidepressants according to prescription popularity were paroxetine (22% and tianeptine (12%. Rate of other antidepressant prescriptions were not higher than 5%. There were differences in antidepressant prescriptions between physicians of different specialties.Conclusion. Reasonable approaches should be used to choose antidepressants. Selective serotonin reuptake inhibitors have benefit for the therapy of concomitant anxious and depressive disorders due to their good tolerability. Nevertheless tricyclic antidepressants are essential in some clinical situations.

  3. [Biomarkers for Mood Disorders and a Novel Antidepressant (R)-ketamine].

    Science.gov (United States)

    Hashimoto, Kenji

    2017-10-01

    Depression is often misdiagnosed as major depressive disorder in patients with bipolar disorder. Therapeutic drugs for these two disorders are quite different, but the anesthetic ketamine shows fast-acting antidepressant effects in treatment-resistant patients with these disorders. Here, we discuss biomarkers for both disorders, recent findings regarding ketamine, and predictable biomarkers for ketamine's antidepressant actions.

  4. Selection and measurement of control antidepressants in clinical tests for Chinese: A systematic review.

    Science.gov (United States)

    Liu, Hao; Yang, Zhi-Min; Geng, Ying; Yang, Huan; Zhao, De-Heng; Xiao, Wei-Dong; Wang, Gao-Hua

    2017-10-01

    The study aims to help domestic application units and research institutions improve their research quality of antidepressant clinical tests by studying and analyzing the current status and problems in selecting control drugs during domestic antidepressant clinical tests and illustrating some key problems that should be noted when selecting the control drug in such researches. Considering the current domestic and overseas status of control drug selection in antidepressant clinical tests, various considerations, and misunderstandings on control drug selection in domestic antidepressant clinical tests were clarified and described, and possible factors that may influence the absolute effect of antidepressants were analyzed. Furthermore, problems that should be noted in selecting control drugs for the antidepressant clinical test, especially the placebo control, were stated. During the antidepressant clinical research, selecting placebo controls conform to moral philosophy and safety requirements. To verify the absolute effect of a test drug, a placebo control should be set or 3-arm tests should be conducted as far as possible. Possible factors that may affect the absolute effect of the test drug, including illness severity of the subject at baseline and research scale, should be given consideration. Application units and research institutions should consider the selection of subjects, control the failure rate, strengthen safety risks, and control and intensify quality control to further improve the overall quality and research level of domestic antidepressant clinical tests.

  5. Selection and measurement of control antidepressants in clinical tests for Chinese

    Science.gov (United States)

    Liu, Hao; Yang, Zhi-Min; Geng, Ying; Yang, Huan; Zhao, De-Heng; Xiao, Wei-Dong; Wang, Gao-Hua

    2017-01-01

    Abstract Objective: The study aims to help domestic application units and research institutions improve their research quality of antidepressant clinical tests by studying and analyzing the current status and problems in selecting control drugs during domestic antidepressant clinical tests and illustrating some key problems that should be noted when selecting the control drug in such researches. Methods: Considering the current domestic and overseas status of control drug selection in antidepressant clinical tests, various considerations, and misunderstandings on control drug selection in domestic antidepressant clinical tests were clarified and described, and possible factors that may influence the absolute effect of antidepressants were analyzed. Furthermore, problems that should be noted in selecting control drugs for the antidepressant clinical test, especially the placebo control, were stated. Results: During the antidepressant clinical research, selecting placebo controls conform to moral philosophy and safety requirements. To verify the absolute effect of a test drug, a placebo control should be set or 3-arm tests should be conducted as far as possible. Possible factors that may affect the absolute effect of the test drug, including illness severity of the subject at baseline and research scale, should be given consideration. Conclusions: Application units and research institutions should consider the selection of subjects, control the failure rate, strengthen safety risks, and control and intensify quality control to further improve the overall quality and research level of domestic antidepressant clinical tests. PMID:29069004

  6. Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr

    2010-01-01

    OBJECTIVE: Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers....... The current study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients. METHOD: Nineteen acutely depressed patients were randomized to receive Epo (40,000 IU) or saline intravenously in a double-blind, parallel-group design. On day 3, we...... assessed neuronal responses to fearful and happy faces using functional magnetic resonance imaging and measured facial expression recognition after the scan. RESULTS: Epo reduced neural response to fearful vs. happy faces in the amygdala and hippocampus, and to fearful faces vs. baseline in superior...

  7. Agent Building Software

    Science.gov (United States)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  8. Prescription of antidepressants to patients on opioid maintenance therapy – a pharmacoepidemiological study

    Directory of Open Access Journals (Sweden)

    Ingeborg Hartz

    2011-12-01

    Full Text Available Background and aims: Depression and anxiety are commonly reported among patients in opioid maintenance treatment (OMT. The aim of the present study was to describe aspects of prescription of antidepresant drug therapy among patients on OMT. Our research questions were: 1 What is the prevalence of antidepressant use according to age and gender? 2 Which antidepressants are used? 3 How are antidepressants used in terms of reimbursement codes, dispensed dose and duration of therapy?Methods: Pharmacoepidemiological data were retrieved from the complete national Norwegian Prescription Database which contains information on all prescription drugs (such as Anatomical Theraputical Chemical (ATC-code, Defined Daily Dose (DDDs, dispensed at pharmacies to individual patients. Norwegian OMT-patients (N=4374, 3035 men and 1339 women who received methadone mixture, buprenorphine capsules or combined buprenorphine-naloxone capsules for at least 6 months in 2009 were included. Prevalence of antidepressant use in the studied patients was measured in terms of retrieval of prescriptions.Results: During 2009 21.7% of the studied patients filled at least one prescription for an antidepressant drugs (men: 21.2%; women: 22.9%. The subgroup of antidepressants most frequently dispensed was selective serotonin reuptake inhibitors (SSRIs (33%, followed by the sedative antidepressants mianserin and mirtazapin (22% and tricyclic antidepressants (TCAs (20%. Except for TCAs, prescriptions of all antidepressant subgroups were reimbursed for either anxiety or depression in 90% of the cases. Overall, 46.9% of the antidepressant users were prescribed antidepressants in the category < 1 DDD per day and/or treatment < 3 months, with no gender difference.Conclusions: About one out of five OMT-patients filled a prescription for an antidepressant drug in 2009. Above 90% had their prescriptions reimbursed for either depression or anxiety. Use at low doses and/or sporadic use among half

  9. Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

    DEFF Research Database (Denmark)

    Galling, B; Vernon, J A; Pagsberg, A K

    2018-01-01

    OBJECTIVE: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. METHODS: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing...... adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval.......77, -0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04-2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation...

  10. Body weight as a predictor of antidepressant efficacy in the GENDEP project

    DEFF Research Database (Denmark)

    Uher, Rudolf; Mors, Ole; Hauser, Joanna

    2009-01-01

    Background: Being overweight or obese may be associated with poor response to antidepressants. The present report explores the moderation of antidepressant response by body weight to establish the specificity to antidepressant mode of action, type of depressive symptoms and gender. Methods: Height....... The relationship between body weight and change in neurovegetative symptoms was moderated by gender with obese men responding less to nortriptyline and obese women having poorer response to both antidepressants. Limitations: As no placebo arm was included, the specificity of findings to antidepressants is relative...... and weight were measured in 797 men and women with major depression treated with escitalopram or nortriptyline for twelve weeks as part of the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Body mass index (BMI) and obesity (BMI > 30) were tested as predictors of change in depressive...

  11. Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian

    2017-01-01

    to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population...... between 1995 and 2010 in the Danish Prescription Register and compared the prevalence and incidence of use of antidepressants, sedatives and antipsychotics. The prevalence of antidepressant use by women was lower in 1998 but no different from that in controls in 2003 and 2008; the prevalence...... of antidepressant use by men was higher in both 1998 and 2008 than in the Danish population. The incidence of antidepressant use was lower for female members in 1996–2000, but no difference was observed in the other periods. The prevalence and incidence of use of sedatives and antipsychotics did not consistently...

  12. Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats.

    Science.gov (United States)

    Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

    2015-03-03

    Depression is one of the most common psychiatric disorders in the world; however, its mechanisms remain unclear. Recently, a new signal-transduction pathway, namely Rho/Rho-kinase signalling, has been suggested to be involved in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However there is no evidence showing the involvement of Rho-kinase pathway in depression. In addition, the infralimbic cortex, rodent equivalent to subgenual cingulate cortex has been shown to be responsible for emotional responses. Thus, in the present study, intracranial guide cannulae were stereotaxically implanted bilaterally into the infralimbic cortex, and the effects of repeated microinjections of a Rho-kinase (ROCK) inhibitor Y-27632 (10 nmol) were investigated in rats. Y-27632 significantly decreased immobility time and increased swimming and climbing behaviors when compared to fluoxetine (10 μg) and saline groups in the forced swim test. In addition, Y-27632 treatment did not affect spontaneous locomotor activity and forelimb use in the open-field and cylinder tests respectively; but it enhanced limb placing accuracy in the ladder rung walking test. Our results suggest that Y-27632 could be a potentially active antidepressant agent. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Competing agents in agent-mediated institutions

    OpenAIRE

    Plaza, Enric; Arcos, Josep Ll.; Noriega, Pablo; Sierra, Carles

    1998-01-01

    Social processes and agent interaction always take place in a specific context. A school of thought in social studies analyses them in the framework of institutions. We present in this paper the notion of agentmediated institutions and show how it is relevant for multi-agent systems (MAS) in general and, more specifically, for MAS that include human agents and software agents involved in socioeconomic interactions. We show how the social interactions of human and software agents taking place ...

  14. Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

    Directory of Open Access Journals (Sweden)

    Shin Minkyu

    2010-11-01

    Full Text Available Abstract Background The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. Results We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine. a selective serotonin reuptake inhibitor (fluoxetine, a monoamine oxidase inhibitor (phenelzine and psychoactive herbal extracts of Nelumbinis Semen (NS. To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced. Conclusions These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

  15. Is the efficacy of antidepressants in panic disorder mediated by adverse events? A mediational analysis.

    Science.gov (United States)

    Bighelli, Irene; Borghesani, Anna; Barbui, Corrado

    2017-01-01

    It has been hypothesised that the perception of adverse events in placebo-controlled antidepressant clinical trials may induce patients to conclude that they have been randomized to the active arm of the trial, leading to the breaking of blind. This may enhance the expectancies for improvement and the therapeutic response. The main objective of this study is to test the hypothesis that the efficacy of antidepressants in panic disorder is mediated by the perception of adverse events. The present analysis is based on a systematic review of published and unpublished randomised trials comparing antidepressants with placebo for panic disorder. The Baron and Kenny approach was applied to investigate the mediational role of adverse events in the relationship between antidepressants treatment and efficacy. Fourteen placebo-controlled antidepressants trials were included in the analysis. We found that: (a) antidepressants treatment was significantly associated with better treatment response (ß = 0.127, 95% CI 0.04 to 0.21, p = 0.003); (b) antidepressants treatment was not associated with adverse events (ß = 0.094, 95% CI -0.05 to 0.24, p = 0.221); (c) adverse events were negatively associated with treatment response (ß = 0.035, 95% CI -0.06 to -0.05, p = 0.022). Finally, after adjustment for adverse events, the relationship between antidepressants treatment and treatment response remained statistically significant (ß = 0.122, 95% CI 0.01 to 0.23, p = 0.039). These findings do not support the hypothesis that the perception of adverse events in placebo-controlled antidepressant clinical trials may lead to the breaking of blind and to an artificial inflation of the efficacy measures. Based on these results, we argue that the moderate therapeutic effect of antidepressants in individuals with panic disorder is not an artefact, therefore reflecting a genuine effect that doctors can expect to replicate under real-world conditions.

  16. Using antidepressants and the risk of stroke recurrence: report from a national representative cohort study.

    Science.gov (United States)

    Juang, Hsiao-Ting; Chen, Pei-Chun; Chien, Kuo-Liong

    2015-06-05

    Evidence about the association between antidepressants and the risk of stroke recurrence was scanty. This study evaluated the risk of stroke recurrence according to using antidepressants in patients with stroke from a national representative cohort. This cohort study followed 16770 patients aged > =20 years who had an incident stroke from 2000 to 2009 from the National Health Insurance Research Database in Taiwan. Records of each antidepressant prescription were obtained during follow-up. The types of antidepressants were categorized by Anatomical Therapeutic Chemical classification system: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and other antidepressants. The main outcome was a recurrent stroke during the follow-up period. The time-dependent Cox proportional hazards model was used in the analyses. During 63715 person-years of follow-up, we documented 3769 events for stroke recurrence. Antidepressants use was associated with an increased risk of stroke recurrence (adjusted hazard ratio [HR], 1.42; 95 % confidence interval [C.I.], 1.24-1.62), especially for ischemic stroke (HR, 1.48; 95 % C.I., 1.28-1.70), but not for hemorrhagic stroke (HR, 1.22; 95 % C.I., 0.86-1.73). The increased risk of stoke recurrence was found for TCAs use only (HR, 1.41; 95 % C.I., 1.14-1.74), SSRIs use only (HR, 1.31; 95 % C.I.,1.00-1.73),use of other types of antidepressants only(HR, 1.46; 95 % C.I.,1.15-1.84), or use of multiple types of antidepressants (HR, 1.84; 95 % C.I.,1.04-3.25). We demonstrated that use of antidepressants was associated with an increased risk of stroke recurrence, especially in ischemic stroke among Taiwanese. Further studies are warranted to confirm the possible underlying mechanisms of these findings.

  17. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis.

    Science.gov (United States)

    Sidor, Michelle M; Macqueen, Glenda M

    2011-02-01

    The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression. EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles. Trials that compared acute (antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch. Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants. Although antidepressants were

  18. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects.

    Science.gov (United States)

    Opal, M D; Klenotich, S C; Morais, M; Bessa, J; Winkle, J; Doukas, D; Kay, L J; Sousa, N; Dulawa, S M

    2014-10-01

    Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling.

  19. Evaluation of antidepressant activity of vanillin in mice.

    Science.gov (United States)

    Shoeb, Ahsan; Chowta, Mukta; Pallempati, Gokul; Rai, Amritha; Singh, Ashish

    2013-01-01

    The main objective of this study was to evaluate antidepressant activity of vanillin in mice models of depression. Animals were divided into five groups, consisting six mice in each group. Out of these, three groups served as control (distilled water, imipramine,and fluoxetine) and the remaining two groups received test drug in two different doses (10 mg/kg and 100 mg/kg). All the drugs were administered orally one hour before the test procedure for acute study and daily for ten days for chronic study. Mice were subjected to forced swim (FST) and tail suspension tests (TST). Both the doses of vanillin reduced the immobility duration in TST as well as in FST. In TST, there was a statistically significant decrease in the immobility in all the groups when compared to the control (distilled water) group. But the reduction of immobility in FST did not show statistically significant reduction in immobility in the groups treated with vanillin when compared with control. In the chronic study group that received vanillin at a dose of 100 mg/kg, the immobility reduction was significantly lower when compared to the group receiving fluoxetine. Vanillin at the dosage of 100 mg/kg has demonstrated antidepressant activity in mice, which is comparable with fluoxetine.

  20. [Suicide, antidepressant prescription and unemployment in Andalusia (Spain)].

    Science.gov (United States)

    Alameda-Palacios, José; Ruiz-Ramos, Miguel; García-Robredo, Beatriz

    2014-01-01

    To analyze the trend in suicide mortality in Andalusia from 1975 to 2012 and its relationship with unemployment and the use of antidepressants. Poisson's segmented regression models were used to estimate changes over time. The association between suicide and the factors examined was measured using Spearman's correlation coefficient. Suicide mortality patterns in men and women are rising. The largest increase was found in people aged from 15 to 44 years, with an annual percentage rate change of 1.21 (95%CI: 0.7-1.7) for men and 0.93 (95%CI: 0.4-1.4) for women. Mortality by suicide has increased in Andalusia since 1975 in all age and gender groups except for women aged 65 years or above. During the last few decades, an upward trend has been observed in young people and a stable or falling trend in the remaining population. Temporary variations in suicide rates are not associated with unemployment rates or with changes in antidepressant prescription. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  1. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Georg Anton Giæver Beiske

    2015-01-01

    Full Text Available Objective. Patients with multiple sclerosis (MS are often suffering from neuropathic pain. Antiepileptic drugs (AEDs and tricyclic antidepressants (TCAs are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females with mean age of 53 (±10 years and EDSS 4.8 (±1.7 used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6% or amitriptyline (9.7%. Polypharmacy was widespread (mean 5.4 drugs with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects.

  2. Risks of using SSRI / SNRI antidepressants during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Dubovicky Michal

    2017-09-01

    Full Text Available At present, affective disorders are among the most commonly diagnosed mental diseases. In pregnancy, they can occur as pre-delivery depression, recurrent depressive disorder or postnatal depression. The estimated prevalence of depressive disorders in pregnancy is approximately 9–16%, with some statistics reporting up to 20%. Approximately 2–3% of pregnant women take antidepressants during pregnancy, and the number of mothers treated increases by birth to 5–7%. Treatment of depression during pregnancy and breastfeeding is a controversial issue, as antidepressants can negatively affect the developing fetus. According to epidemiological studies, the effects of treated depression in pregnancy are related to premature birth, decreased body weight of the child, intrauterine growth retardation, neonatal adaptive syndrome, and persistent pulmonary hypertension. However, untreated depression can adversely affect maternal health and increase the risk of preeclampsia and eclampsia, as well as of subsequent postnatal depression, which can lead to disruption of the mother-child relationship. Based on the above mentioned facts, the basic question arises as to whether or not to treat depression during pregnancy and lactation.

  3. Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis.

    Science.gov (United States)

    Abdelhalim, Abeer; Karim, Nasiara; Chebib, Mary; Aburjai, Talal; Khan, Imran; Johnston, Graham A R; Hanrahan, Jane

    2015-01-01

    Rosmarinus officinalis, traditionally known as rosemary, has been widely used in traditional medicines and has long been known as the herb of remembrance. However, few studies have investigated the effects of non-volatile components of rosemary on central nervous system function. Fractionation of R. officinalis led to the isolation of salvigenin, rosmanol and cirsimaritin, which were investigated in mouse models of acute toxicity, antinociception (tail immersion and hot plate tests), depression (tail suspension and forced swim tests) and anxiety (elevated plus maze and light/dark box paradigms). Rosmanol, cirsimaritin and salvigenin were not found to exhibit any signs of acute toxicity (50-200 mg/kg), but elicited antinociceptive, antidepressant and anxiolytic activities. Rosmanol, cirsimaritin and salvigenin, all previously shown to have biphasic modulation of GABAA receptors, demonstrated CNS activity in mouse models of antinociception, antidepressant and anxiolysis. The anxiolytic activity of all three compounds was not ameliorated by flumazenil, but was inhibited by pentylenetetrazol, suggesting a mode of action via GABAA receptors at a site other than the high affinity benzodiazepine binding site. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  4. Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons

    Directory of Open Access Journals (Sweden)

    Nadine eBeckmann

    2014-09-01

    Full Text Available Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer’s disease and major depression, as well as viral (e.g. measles virus and bacterial (e.g. Staphylococcus aureus, Pseudomonas aeruginosa infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug.

  5. Factors associated with switching and combination use of antidepressants in young Swedish adults

    Science.gov (United States)

    Andersson Sundell, K; Petzold, M G; Wallerstedt, S M

    2013-01-01

    Aims Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20–34 years. Methods Individuals, aged 20–34 years, who purchased an antidepressant in January–June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. Results A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93–2.57), and lower in individuals with high education: 0.64 (0.54–0.75), and shorter length of follow-up: 0.73 (0.62–0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05–2.49), and lower among individuals with short university education: 0.58 (0.43–0.78), those starting on mirtazapine: 0.78 (0.62–0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63–0.88). Conclusions One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase

  6. Factors associated with switching and combination use of antidepressants in young Swedish adults.

    Science.gov (United States)

    Andersson Sundell, K; Petzold, M G; Wallerstedt, S M

    2013-12-01

    Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20-34 years. Individuals, aged 20-34 years, who purchased an antidepressant in January-June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93-2.57), and lower in individuals with high education: 0.64 (0.54-0.75), and shorter length of follow-up: 0.73 (0.62-0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05-2.49), and lower among individuals with short university education: 0.58 (0.43-0.78), those starting on mirtazapine: 0.78 (0.62-0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63-0.88). One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase patterns were associated with socioeconomic

  7. Antidepressant effects on emotional temperament: toward a biobehavioral research paradigm for major depressive disorder.

    Science.gov (United States)

    Soskin, David P; Carl, Jenna R; Alpert, Jonathan; Fava, Maurizio

    2012-06-01

    Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause-correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. Preliminary findings appear to support the cause-correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive-behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects. © 2012 Blackwell Publishing Ltd.

  8. Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

    Directory of Open Access Journals (Sweden)

    Elsbeth Jensen-Otsu

    2015-11-01

    Full Text Available Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005–2006 National Health and Nutrition Examination Survey (NHANES. Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E. 215 ± 73 kcal/day compared to non-users (p = 0.01. There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09–2.90, but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.

  9. Pregnancy and postpartum antidepressant use moderates the effects of sleep on depression.

    Science.gov (United States)

    Stone, Kristen C; Salisbury, Amy L; Miller-Loncar, Cynthia L; Mattera, Jennifer A; Battle, Cynthia L; Johnsen, Dawn M; O'Grady, Kevin E

    2017-10-01

    This study examined the course of antidepressant use, sleep quality, and depression severity from pregnancy through 6-month postpartum in women with and without a depressive disorder during pregnancy. Women (N = 215) were interviewed during pregnancy, 1- and 6-month postpartum. Mixed linear models were used to examine the longitudinal course and inter-relationships for the time-varying variables of antidepressant use, subjective sleep quality, and depression severity. Pregnant women with a depressive disorder who did not use antidepressants had more variable depression severity over time with improvements in depression severity by 6-month postpartum. In contrast, the depression severity of their medicated counterparts remained stable and high throughout. Pregnant women without a depressive disorder had worse sleep quality when using antidepressants compared with when they were not. Antidepressant use significantly strengthened the magnitude of the effect of sleep quality on depression severity in women with a depressive disorder during pregnancy. When prenatally depressed women use antidepressants, their sleep disturbance is more highly linked to depression severity than when they do not. Furthermore, antidepressants are not adequately treating the sleep disturbance of these women or their remitted counterparts, leaving both groups vulnerable to significant negative mental and physical health outcomes.

  10. Placental and fetal effects of antenatal exposure to antidepressants or untreated maternal depression.

    Science.gov (United States)

    Gentile, Salvatore; Fusco, Maria Luigia

    2017-05-01

    To assess systematically the effects of antidepressants and untreated maternal depression on human placenta and the developing fetus. Pertinent medical literature information was identified using MEDLINE/PubMed, SCOPUS and EMBASE. Electronic searches, limited to human studies published in English, provided 21 studies reporting primary data on placental and fetal effects of antidepressant exposure or untreated gestational depression. The impact of antidepressants and non-medicated maternal depression on placental functioning and fetal biochemical architecture seems to be demonstrated, although its clinical significance remains unclear. More robust data seem to indicate that exposure to either antidepressants or untreated maternal depression may induce epigenetic changes and interfere with the physiological fetal behavior. Two cases of iatrogenic fetal tachyarrhythmia have also been reported. Future research should clarify the clinical relevance of the impact of antidepressant and untreated maternal depression exposure on placental functioning. Moreover, ultrasound studies investigating fetal responses to antidepressants or maternal depressive symptoms are mandatory. This assessment should be performed during the whole duration of gestational period, when different fetal behavioral patterns become progressively detectable. Analyses of biochemical and epigenetic modifications associated with maternal mood symptoms and antidepressant treatment should also be implemented.

  11. Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

    Science.gov (United States)

    Haastrup, Eva; Grau, Katrine; Eugen-Olsen, Jesper; Thorball, Christian; Kessing, Lars Vedel; Ullum, Henrik

    2014-01-01

    Objectives Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. Methods suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register. Results For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11–2.69). For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45–2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002). Conclusions High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression. PMID:25329298

  12. Low Risk for Switch to Mania during Treatment with Sleep Promoting Antidepressants.

    Science.gov (United States)

    Wichniak, A; Jarkiewicz, M; Okruszek, Ł; Wierzbicka, A; Holka-Pokorska, J; Rybakowski, J K

    2015-05-01

    Sleep-promoting antidepressants are of interest because they are used not only as antidepressants, but also to promote sleep. We reviewed case reports describing the switch to mania during treatment with trazodone, mirtazapine, or agomelatine. Trazodone, mirtazapine, and agomelatine may induce manic symptoms. However, the risk of switching is related, first of all, to doses recommended for antidepressant treatment, administered without mood-stabilizer co-therapy. Low doses of these antidepressants, used for their hypnotic or sedative effects, were observed to cause mania only in patients with other risk factors for switching. There is no evidence for trazodone or mirtazapine and only sparse evidence for agomelatine, claiming that treatment with these antidepressants is related to an increased risk of switching to mania when administered in combination with a mood stabilizer. These findings suggest that low doses of trazodone and mirtazapine are safe in bipolar disorder, and should still be considered important alternatives to hypnotics when long-term pharmacological treatment of insomnia is necessary. It seems that these antidepressants and agomelatine can also be used safely in antidepressant doses when combined with a mood stabilizer. © Georg Thieme Verlag KG Stuttgart · New York.

  13. The discovery of antidepressant drugs by computer-analyzed human cerebral bio-electrical potentials (CEEG).

    Science.gov (United States)

    Itil, T M

    1983-01-01

    Antidepressant properties of six compounds were predicted based on their computer-analyzed human electroencephalographical (CEEG) profiles. The clinical investigations with mianserin (GB-94) confirmed the CEEG prediction. This compound has now been marketed as the first antidepressant of which the clinical effects were discovered solely by the quantitative pharmaco-EEG method. As predicted by the CEEG, clinical antidepressant properties of GC-46, mesterolone, and estradiol valerate were observed in preliminary investigations. No extensive studies with definite statistical results were yet carried out with these compounds. No systematic large studies could be conducted with cyclozocine and cyproterone acetate because of the intolerable side effects with these compounds. The optical isomers of mianserin, GF-59 and GF-60, both predicted as antidepressant by the computer EEG data base, have not yet been tested in depressive patients. None of these compounds possess the "typical" pharmacological and/or biochemical profiles of marketed antidepressants. Thus, the discovery of the established antidepressant properties of mianserin (GB-94) by computer analyzed EEG method challenges the well-known biochemical hypotheses of depression and the "classical" development of antidepressant drugs.

  14. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

    Directory of Open Access Journals (Sweden)

    Elena eNosyreva

    2014-12-01

    Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

  15. Antidepressant-induced lipidosis with special reference to tricyclic compounds.

    Science.gov (United States)

    Xia, Z; Ying, G; Hansson, A L; Karlsson, H; Xie, Y; Bergstrand, A; DePierre, J W; Nässberger, L

    2000-04-01

    Cationic amphiphilic drugs, in general, induce phospholipid disturbances. Tricyclic, as well as other antidepressants belong to this group. In experimental animals, antidepressants induce lipid storage disorders in cells of most organs, a so-called generalized phospholipidosis. This disorder is conveniently detected by electron microscopic examination revealing myelin figures. Myelin figures or myeloid bodies are subcellular organelles containing unicentric lamellar layers. The lipidotic induction potency during in vivo is related to the apolarity of the compound. Metabolism of phospholipids takes place within the cell continuously. Several underlying mechanisms may be responsible for the induction of the phospholipid disturbance. For instance, it has been suggested that the compounds bind to phospholipids and such binding may alter the phospholipid's suitability as a substrate for phospholipases. Free TCA or metabolites thereof may also inhibit phospholipases directly, as has been demonstrated for sphingomyelinase in glioma and neuroblastoma cells. Both these mechanisms might result in phospholipidosis. Interaction between drug and phospholipid bilayer has been investigated by nuclear magnetic resonance technique. There seems to be large differences in the sensitivities amongst different organs. Steroid-producing cells of the adrenal cortex, testis and ovaries are in particular susceptible to drug-induced lipidosis. The so-called foam cells are lung macrophages located in the interstitium which become densely packed with myelin figures during TCA exposure. It requires about 3-6 weeks of treatment to develop this converted cell. In cell cultures however, phospholipidosis is demonstrated already after 24 h only. It appears that the cells that undergo TCA-induced lipidosis may recover after withdrawal of the drug. The time required to achieve complete recovery ranges from 3-4 weeks to several months, depending on the organ affected. Little is known about the

  16. Temporal changes in suicide rates for persons treated and not treated with antidepressants in Denmark during 1995-1999

    DEFF Research Database (Denmark)

    Søndergård, L; Kvist, K; Lopez, A G

    2006-01-01

    OBJECTIVE: To compare the temporal changes in suicide rate among patients treated with antidepressants with the change in suicide rate among persons who have not been treated with antidepressants during 1995-1999. METHOD: In a historic prospective national pharmacoepidemiological register linkage...... study by using four Danish registers we included 438,625 patients who had purchased antidepressants, and compared them with 1,199,057 population based control persons. The annual rate of suicide was estimated using Poisson regression analyses. RESULTS: The suicide rate decreased for persons treated...... with antidepressants as well as for persons not treated with antidepressants. The proportion of persons, who committed suicide and who had not been treated with antidepressants decreased. The reduction in suicide rate was more pronounced among persons treated with SSRIs or older antidepressants than among persons...

  17. Use of antipsychotic and antidepressant within the Psychiatric Disease Centre, Regional Health Service of Ferrara.

    Science.gov (United States)

    Bianchi, Stefano; Bianchini, Erica; Scanavacca, Paola

    2011-12-20

    This study aimed at describing the type and dosage of psychopharmaceuticals dispensed to patients with psychiatric disorders and to assess the percentage of patients treated with antipsychotics and antidepressants, the associated therapies, treatment adherence, and dosages used in individuals registered at the Psychiatric Disease Center (PDC), Regional Health Service of Ferrara. The analysis focused on therapeutic programmes presented to the Department of Pharmacy of the University Hospital of Ferrara of 892 patients treated by the PDC (catchment area of 134605 inhabitants). All diagnoses were made according to International Classification of Diseases (ICD-9). The analysis focused on prescriptions from September 2007 to June 2009. Data on adherence to prescribed therapy have were processed by analysis of variance. Among the patients 63% were treated with antipsychotics and 40% with antidepressants. Among patients receiving antipsychotics 92% used second-generation antipsychotics (SGAs) whereas the remaining 8% used first generation antipsychotics (FGAs). Antipsychotic doses were lower than Daily Defined Dose (DDDs), and SGAs were often given with anticholinergics to decrease side effects. Mean adherence to antipsychotic therapy was 64%. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were the most often prescribed, 55%. Dosages of these were within the limits indicated by the technical datasheet but higher than DDDs. Only 26% of patients underwent monotherapy. In antidepressants polytherapy, medication was associated with another antidepressant, 6% or with an antipsychotic, 51%. Mean adherence to the antidepressant therapy was 64%. Patients treated with antipsychotics tend to use doses lower than DDDs. The opposite tendency was noted in patients treated with antidepressants. Only a small percentage of patients (14%) modified their neuroleptic therapy by increasing the dosage. On the contrary, patients treated with antidepressants mainly

  18. Assessing disruptions in adherence to antidepressant treatments after breast cancer diagnosis.

    Science.gov (United States)

    Chou, Yi-Ting; Winn, Aaron N; Rosenstein, Donald L; Dusetzina, Stacie B

    2017-06-01

    Long-term treatment with antidepressants can lessen the symptoms of depression, but health-related crises-such as a cancer diagnosis-may disrupt ongoing depression care. The study aims to estimate the effect of receiving a breast cancer diagnosis on antidepressant adherence among women with depression. Using SEER-Medicare administrative claims, we identified women aged 65+ with newly diagnosed breast cancer between 2008 and 2011, who were diagnosed with depression and used antidepressants during the year before pre-diagnosis year. We compared antidepressant adherence among women with breast cancer to similar women without cancer using generalized estimation equations. Antidepressant adherence was estimated using the proportion of days covered 1 year before and after the index date. We included 1142 women with breast cancer and pre-existing depression and 1142 matched non-cancer patients with pre-existing depression. Mean antidepressant adherence was similar for both groups in the year before and after the index date (all around 0.71); adherence decreased by approximately 0.01 following breast cancer diagnosis in cancer group, with similar reductions among non-cancer group (p = 0.19). However, substantial proportion of patients had inadequate adherence to antidepressants in the post-diagnosis period, and almost 40% of patients in each group discontinued antidepressants over the study period. Antidepressant adherence was not associated with receiving a breast cancer diagnosis beyond what would have been expected in a similar cohort of women without cancer; however, adherence was poor among both groups. Ensuring adequate ongoing depression care is important to improve cancer care and patient quality of life in the long term. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Safety limits of antidepressant use plus combinations: focus on cardiovascular function.

    Science.gov (United States)

    Stella, Florindo; Loureiro, Julia C; Pais, Marcos V; Canineu, Paulo R; Florenza, Orestes V

    2017-12-27

    Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Antidepressants and the risk of hyponatremia: a class-by-class review of literature.

    Science.gov (United States)

    De Picker, Livia; Van Den Eede, Filip; Dumont, Glenn; Moorkens, Greta; Sabbe, Bernard G C

    2014-01-01

    Antidepressant-induced hyponatremia can cause significant morbidity and mortality. It is mostly associated with the use of selective serotonin reuptake inhibitors (SSRIs), but its frequency and class specificity are uncertain. To determine the relationship between hyponatremia and antidepressants and to define the incidence and odds ratios for antidepressant classes. A review of the literature prior to March 2013 was performed using Web of Science and PubMed by employing combinations of search strings "antidepressants" and antidepressant class and generic drug names with "hyponatr(a)emia," "SIADH," or "inappropriate ADH." Overall, 21 effect studies and more than 100 case reports were considered, most concerning SSRIs. Because of variations in study designs, populations, and cutoff values, incidence rates diverged between 0.06% and 40% for SSRIs and 0.08% and 70% for venlafaxine. Although based on less solid evidence, incidence figures for mirtazapine and tricyclic antidepressants were lower. Regarding classes, odds ratios for SSRIs (1.5-21.6) were consistently higher than for tricyclic antidepressants (TCAs) (1.1-4.9). The risks associated with monoamine oxidase inhibitors, reboxetine, and bupropion could not be established owing to insufficient information. Patient risk factors included older age (odds ratios = 6.3) and concomitant use of (thiazide) diuretics (odds ratios = 11.2-13.5). Hyponatremia is a potentially dangerous side effect of antidepressants and is not exclusive to SSRIs. Current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine, especially when combined with patient risk factors, warranting clinicians to be aware of this complication. The risks associated with mirtazapine are moderate, supporting this antidepressant as an alternative treatment for patients with (an increased risk of) hyponatremia. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  1. Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

    Science.gov (United States)

    Mika, Joanna; Zychowska, Magdalena; Makuch, Wioletta; Rojewska, Ewelina; Przewlocka, Barbara

    2013-01-01

    The current knowledge of the pharmacological actions of the tricyclic antidepressants (TCAs) has slowly evolved through their over 40-year history. Chronic pain represents one of the most important public health problems, and antidepressants are an essential part of the therapeutic strategy in addition to classical analgesics. This article reviews the available evidence on the efficacy and safety of antidepressants in chronic pain conditions; namely, headaches, low back pain, fibromyalgia, cancer pain and especially neuropathic pain. TCAs are traditionally the main type of depression medication used to treat chronic pain. Recently, new antidepressants were introduced into clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs that are effective for chronic pain belong to the tetracyclic antidepressants (TeCAs) group (amoxapine, maprotiline), the serotonin and noradrenaline reuptake inhibitors (SNRIs) group (duloxetine, venlafaxine, milnacipran) and the atypical antidepressants group (bupropion, trazodone, mirtazapine, nefazodone). In this review, we present the available publications on TCAs (amitriptyline, doxepin, imipramine, desipramine, nortriptyline), TeCAs (amoxapine, maprotiline), selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, paroxetine), SNRIs (duloxetine, venlafaxine, milnacipran) and atypical antidepressants (bupropion) for the treatment of neuropathic pain. We also review analgesics acting as both opioid receptor agonists and also acting as aminergic reuptake inhibitors. Existing data are insufficient to conclude which of these new classes of antidepressants has the best clinical profile and will be the most effective in the treatment of neuropathic pain; in addition, a lower incidence of side effects should be considered. Increased experimental and translational research is a key for further improvement of the treatment of chronic pain with antidepressants. However

  2. Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis.

    Science.gov (United States)

    Xu, X-M; Yang, C; Liu, Y; Dong, M-X; Zou, D-Z; Wei, Y-D

    2017-08-01

    Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature. A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index. Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of -0.79 [95% confidence interval (CI) -1.13 to -0.45, P antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97-2.02; P = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05-2.89, P = 0.03). Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky. © 2017 EAN.

  3. Modulation of muscarinic system with serotonin-norepinephrine reuptake inhibitor antidepressant attenuates depression in mice

    Science.gov (United States)

    Singh, Paramdeep; Singh, Thakur Gurjeet

    2015-01-01

    Objective: Several studies suggest that muscarinic receptor antagonist scopolamine is a rapidly acting antidepressant for the treatment-resistant depression. Therefore, this study was carried out to investigate the possibility of synergistic potential of scopolamine with antidepressants for the treatment of depression without memory impairment in mice. Materials and Methods: Antidepressants such as citalopram, duloxetine, fluvoxamine, and venlafaxine at their median effective dose that is 12.5, 42.8, 17.5, 15.7 mg/kg p.o., respectively, were evaluated in combination with scopolamine 0.2 mg/kg intraperitoneally for the synergistic potential for ameliorating depression in Swiss albino mice. A battery of tests including forced swim test (FST) and tail suspension test (TST) were performed in all the groups comprising vehicle control, scopolamine, antidepressants per se, and the combinations of antidepressants with scopolamine. This was followed by the locomotor activity and memory tests. Results: Behavioral studies indicated that only antidepressant venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility time compared to the vehicle control in FST and TST, respectively. This is significant (P antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment effects in antidepressant paradigms. All the data were evaluated using the one-way analysis of variance followed by individual comparisons using Tukey's post-hoc test. Control open field studies demonstrated no significant increase in general locomotion after co-administration of the compounds. Step down avoidance paradigm confirmed that scopolamine at the selected dose has no cognition deficit in any mice. Conclusions: The dose of scopolamine selected for synergistic potential has no detrimental effect on memory. The present results suggest the concoction of scopolamine with venlafaxine for enhanced synergistic antidepressive effects with the reduction of dose. PMID

  4. Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study.

    Directory of Open Access Journals (Sweden)

    Ricardo Gusmão

    Full Text Available Research concerning the association between use of antidepressants and incidence of suicide has yielded inconsistent results and is the subject of considerable controversy. The first aim is to describe trends in the use of antidepressants and rates of suicide in Europe, adjusted for gross domestic product, alcohol consumption, unemployment, and divorce. The second aim is to explore if any observed reduction in the rate of suicide in different European countries preceded the trend for increased use of antidepressants.Data were obtained for 29 European countries between 1980 and 2009. Pearson correlations were used to explore the direction and magnitude of associations. Generalized linear mixed models and Poisson regression distribution were used to clarify the effects of antidepressants on suicide rates, while an autoregressive adjusted model was used to test the interaction between antidepressant utilization and suicide over two time periods: 1980-1994 and 1995-2009.An inverse correlation was observed in all countries between recorded Standardised Death Rate (SDR for suicide and antidepressant Defined Daily Dosage (DDD, with the exception of Portugal. Variability was marked in the association between suicide and alcohol, unemployment and divorce, with countries depicting either a positive or a negative correlation with the SDR for suicide. Every unit increase in DDD of an antidepressant per 1000 people per day, adjusted for these confounding factors, reduces the SDR by 0.088. The correlation between DDD and suicide related SDR was negative in both time periods considered, albeit more pronounced between 1980 and 1994.Suicide rates have tended to decrease more in European countries where there has been a greater increase in the use of antidepressants. These findings underline the importance of the appropriate use of antidepressants as part of routine care for people diagnosed with depression, therefore reducing the risk of suicide.

  5. Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study

    Science.gov (United States)

    Gusmão, Ricardo; Quintão, Sónia; McDaid, David; Arensman, Ella; Van Audenhove, Chantal; Coffey, Claire; Värnik, Airi; Värnik, Peeter; Coyne, James; Hegerl, Ulrich

    2013-01-01

    Background Research concerning the association between use of antidepressants and incidence of suicide has yielded inconsistent results and is the subject of considerable controversy. The first aim is to describe trends in the use of antidepressants and rates of suicide in Europe, adjusted for gross domestic product, alcohol consumption, unemployment, and divorce. The second aim is to explore if any observed reduction in the rate of suicide in different European countries preceded the trend for increased use of antidepressants. Methods Data were obtained for 29 European countries between 1980 and 2009. Pearson correlations were used to explore the direction and magnitude of associations. Generalized linear mixed models and Poisson regression distribution were used to clarify the effects of antidepressants on suicide rates, while an autoregressive adjusted model was used to test the interaction between antidepressant utilization and suicide over two time periods: 1980–1994 and 1995–2009. Findings An inverse correlation was observed in all countries between recorded Standardised Death Rate (SDR) for suicide and antidepressant Defined Daily Dosage (DDD), with the exception of Portugal. Variability was marked in the association between suicide and alcohol, unemployment and divorce, with countries depicting either a positive or a negative correlation with the SDR for suicide. Every unit increase in DDD of an antidepressant per 1000 people per day, adjusted for these confounding factors, reduces the SDR by 0.088. The correlation between DDD and suicide related SDR was negative in both time periods considered, albeit more pronounced between 1980 and 1994. Conclusions Suicide rates have tended to decrease more in European countries where there has been a greater increase in the use of antidepressants. These findings underline the importance of the appropriate use of antidepressants as part of routine care for people diagnosed with depression, therefore reducing the

  6. International variation in drug utilization: Antidepressant utilization in North America, Greece, and Ireland

    Directory of Open Access Journals (Sweden)

    Muhammad Mamdani

    2013-01-01

    Materials and Methods: We conducted a population-based cross-sectional time series analysis of antidepressant utilization in Canada, the United States, Greece, and Ireland from January 2007 to September 2011 using data from IMS Healthcare Inc., which tracks over 80% of global prescription sales of over 1.3 million products. We studied 23 antidepressants from five drug classes, namely, 1 serotonin-specific reuptake inhibitors (SSRIs, 2 serotonin-norepinephrine reuptake inhibitors (SNRIs, 3 tricyclic antidepressants (TCAs, 4 monoamine oxidase inhibitors (MAOIs, and 5 ′other′ antidepressants. We used time series analysis to examine trends in utilization patterns. Results: Overall antidepressant utilization increased steadily over time for all study regions, although regions differed considerably in the magnitude of antidepressant utilization and the rates of increase. While overall antidepressant utilization rates were similar between Canada (2,876 units per 1,000 population per month and the United States (2,815 units per 1,000 population per month, these rates were approximately 83% higher than in Greece (1,558 units per 1,000 population per month and approximately 50% higher than in Ireland (1,898 units per 1,000 population per month. Although the use of SSRIs, SNRIs, and other antidepressants generally increased over time, the use of TCAs and MAOIs generally decreased over time. Utilization of specific drug classes varied widely between regions, ranging from an 80% relative difference in SSRI utilization between the United States and Greece to a nearly 700% difference in the utilization of MAOIs between Canada and the United States. Conclusions: The findings of our study, using antidepressants as the case example, are consistent with previous studies demonstrating significant variation in drug utilization levels internationally. Future studies are needed to document regional variation in light of appropriateness of drug therapies to determine optimal

  7. The biological effects of antidepressants on the molluscs and crustaceans: a review.

    Science.gov (United States)

    Fong, Peter P; Ford, Alex T

    2014-06-01

    Antidepressants are among the most commonly detected human pharmaceuticals in the aquatic environment. Since their mode of action is by modulating the neurotransmitters serotonin, dopamine, and norepinephrine, aquatic invertebrates who possess transporters and receptors sensitive to activation by these pharmaceuticals are potentially affected by them. We review the various types of antidepressants, their occurrence and concentrations in aquatic environments, and the actions of neurohormones modulated by antidepressants in molluscs and crustaceans. Recent studies on the effects of antidepressants on these two important groups show that molluscan reproductive and locomotory systems are affected by antidepressants at environmentally relevant concentrations. In particular, antidepressants affect spawning and larval release in bivalves and disrupt locomotion and reduce fecundity in snails. In crustaceans, antidepressants affect freshwater amphipod activity patterns, marine amphipod photo- and geotactic behavior, crayfish aggression, and daphnid reproduction and development. We note with interest the occurrence of non-monotonic dose responses curves in many studies on effects of antidepressants on aquatic animals, often with effects at low concentrations, but not at higher concentrations, and we suggest future experiments consider testing a broader range of concentrations. Furthermore, we consider invertebrate immune responses, genomic and transcriptomic sequencing of invertebrate genes, and the ever-present and overwhelming question of how contaminant mixtures could affect the action of neurohormones as topics for future study. In addressing the question, if antidepressants affect aquatic invertebrates at concentrations currently found in the environment, there is strong evidence to suggest the answer is yes. Furthermore, the examples highlighted in this review provide compelling evidence that the effects could be quite multifaceted across a variety of biological

  8. Prevalence of antidepressant prescription or use in patients with acute coronary syndrome: a systematic review.

    Directory of Open Access Journals (Sweden)

    Matthew J Czarny

    Full Text Available Depression is common among acute coronary syndrome (ACS patients and is associated with poor prognosis. Cardiac side effects of older antidepressants were well-known, but newer antidepressants are generally thought of as safe to use in patients with heart disease. The objective was to assess rates of antidepressant use or prescription to patients within a year of an ACS.PubMed, PsycINFO, and CINAHL databases searched through May 29, 2009; manual searching of 33 journals from May 2009 to September 2010. Articles in any language were included if they reported point or period prevalence of antidepressant use or prescription in the 12 months prior or subsequent to an ACS for ≥100 patients. Two investigators independently selected studies for inclusion/exclusion and extracted methodological characteristics and outcomes from included studies (study setting, inclusion/exclusion criteria, sample size, prevalence of antidepressant prescription/use, method of assessing antidepressant prescription/use, time period of assessment.A total of 24 articles were included. The majority were from North America and Europe, and most utilized chart review or self-report to assess antidepressant use or prescription. Although there was substantial heterogeneity in results, overall, rates of antidepressant use or prescription increased from less than 5% prior to 1995 to 10-15% after 2000. In general, studies from North America reported substantially higher rates than studies from Europe, approximately 5% higher among studies that used chart or self-report data.Antidepressant use or prescription has increased considerably, and by 2005 approximately 10% to 15% of ACS patients were prescribed or using one of these drugs.

  9. Antidepressant Medication Use and Risk of Hyperglycemia and Diabetes Mellitus—A Noncausal Association?

    Science.gov (United States)

    Kivimäki, Mika; Batty, G. David; Jokela, Markus; Ebmeier, Klaus P.; Vahtera, Jussi; Virtanen, Marianna; Brunner, Eric J.; Tabak, Adam G.; Witte, Daniel R.; Kumari, Meena; Singh-Manoux, Archana; Hamer, Mark

    2011-01-01

    Background Previous research suggests a link between antidepressant use and diabetes, but it is unclear whether the association is causal or attributable to detection/ascertainment bias. To examine this, we assessed the associations of antidepressant use with change in glucose levels and incidence of undiagnosed and diagnosed diabetes. Methods During an 18-year period, we monitored antidepressant use, glucose levels, and diabetes status in 5978 civil servants (70.9% male, age range 39–64 years) free of diabetes at baseline (the Whitehall II study). Use of medication and plasma glucose were assessed at four study screenings: 1991/1993, 1997/1999, 2003/2004, and 2008/2009. Incident diabetes cases were classified as either diagnosed (n = 294) if detected using self-report of physician diagnosis and/or the use of diabetes medication or undiagnosed (n = 346) if detected based on fasting and/or 2-hour postload glucose levels using an oral glucose tolerance test at the study screenings. Results Incidence of diagnosed diabetes was higher among antidepressant users than nonusers (odds ratio 3.10, 95% confidence interval: 1.66–5.78). However, antidepressant use was not associated with undiagnosed diabetes at any follow-up examination nor with higher fasting or 2-hour postload plasma glucose levels or increasing glucose levels over time. Odds ratio for undiagnosed diabetes for antidepressant users versus nonusers was .88 (95% confidence interval: .45–1.72, p = .70). The mean difference in glucose changes between participants reporting antidepressant use at three screenings compared with those not on antidepressant treatment was .0 mmol/L. Conclusions The link between antidepressant use and diabetes risk may not be causal in nature. PMID:21872216

  10. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan.

    Directory of Open Access Journals (Sweden)

    Linda Nguyen

    Full Text Available Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1 receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047 were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3H](+-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.

  11. Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

    International Nuclear Information System (INIS)

    Malatynska, E.; Knapp, R.J.; Ikeda, M.; Yamamura, H.I.

    1988-01-01

    Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated 36 Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced by them

  12. Spadin, a Sortilin-derived peptide: a new concept in the antidepressant drug design

    Directory of Open Access Journals (Sweden)

    Heurteaux Catherine

    2011-07-01

    Full Text Available Depression is the most common of psychiatric illnesses. The design of effective treatments for this disorder is a challenging process. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. Deletion of TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate the fast antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the sortilin receptor and acting through TREK-1 inhibition.

  13. Mortality in major affective disorder: relationship to subtype of depression. The Danish University Antidepressant Group

    DEFF Research Database (Denmark)

    Buchholtz-Hansen, P E; Wang, A G; Kragh-Sørensen, P

    1993-01-01

    of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of > or = 18 and/or a Hamilton subscale score of > or = 9. Diagnostic classification...... a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk in the first 3 years...

  14. Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: A case report

    Directory of Open Access Journals (Sweden)

    Hassan Amiri

    2016-12-01

    Full Text Available Poisoning with tricyclic antidepressants is an important cause of drug-related self-poisoning in the developed world and a very common cause of poisoning and mortality in developing countries. Electrocardiographic manifestations of most tricyclic antidepressant-poisoned patients resolve by the administration of 1–2 mEq/kg of sodium bicarbonate. Some rare cases have been reported who have been resistant to the long-term or high doses of bicarbonate administration. We present a case of acute tricyclic antidepressant toxicity referring with status epilepticus, hypotension, and refractory QRS complex widening that resolved after the intravenous administration of 2650 mEq sodium bicarbonate.

  15. Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

    DEFF Research Database (Denmark)

    Madsen, M. B.; Kogelman, L. J. A.; Kadarmideen, H. N.

    2018-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel...... the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4......) compared with the subsequent period (4-8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment. The strongest interactions in the initial SSRI treatment period involved genes encoding transcriptional factors, and in the subsequent period...

  16. Synthesis and anti-depressant evaluation of novel pyrazolone derivatives

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Merugumolu

    2016-06-01

    Full Text Available Diazotization of substituted anilines with NaNO2 and concentrated hydrochloric acid at 0ºC gave the diazonium chlorides. Coupling of substituted aryl diazonium chlorides with ethyl acetoacetate in methanol gave ethyl-2-aryl-hydrazono-3-oxobutyrates (2a-h. Reaction of (2a-h with naphthoic carbohydrazide (3 gave the title compounds pyrazolone derivatives (4a-h. The newly synthesized compounds were screened for their in vivo anti-depressant activity by tail suspension test and forced swimming test. Some of the tested compounds 4f, 4g showed very good activity when compared to the standard drug imipramine. The newly synthesized compounds were characterized by physical parameters and the structures were elucidated by spectral data.

  17. Moderation of antidepressant response by the serotonin transporter gene

    DEFF Research Database (Denmark)

    Huezo-Diaz, Patricia; Uher, Rudolf; Smith, Rebecca

    2009-01-01

    Background: There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR...... is modulated by gender, age and other variants in the serotonin transporter gene. Aims: To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). Method: The 5-HTTLPR and 13 additional markers across...... the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Results: The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more...

  18. Profitable failure: antidepressant drugs and the triumph of flawed experiments.

    Science.gov (United States)

    McGoey, Linsey

    2010-01-01

    Drawing on an analysis of Irving Kirsch and colleagues' controversial 2008 article in "PLoS [Public Library of Science] Magazine" on the efficacy of SSRI antidepressant drugs such as Prozac, I examine flaws within the methodologies of randomized controlled trials (RCTs) that have made it difficult for regulators, clinicians and patients to determine the therapeutic value of this class of drug. I then argue, drawing analogies to work by Pierre Bourdieu and Michael Power, that it is the very limitations of RCTs -- their inadequacies in producing reliable evidence of clinical effects -- that help to strengthen assumptions of their superiority as methodological tools. Finally, I suggest that the case of RCTs helps to explore the question of why failure is often useful in consolidating the authority of those who have presided over that failure, and why systems widely recognized to be ineffective tend to assume greater authority at the very moment when people speak of their malfunction.

  19. Common mechanisms of pain and depression: are antidepressants also analgesics?

    Czech Academy of Sciences Publication Activity Database

    Nekovářová, Tereza; Yamamotová, A.; Valeš, Karel; Stuchlík, Aleš; Fricová, J.; Rokyta, R.

    2014-01-01

    Roč. 8, Mar 25 (2014), s. 99 ISSN 1662-5153 R&D Projects: GA MZd(CZ) NT13386; GA MZd(CZ) NT13403; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP303/12/1464 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204; GA MZd(CZ) NT14484; Univerzita Karlova(CZ) Prvouk P34; GA MŠk(CZ) CSM7/CRP/2014 Institutional support: RVO:67985823 Keywords : chronic pain * depression * antidepressant * neuroplasticity * default mode network Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  20. Do depressed patients on adjunctive atypical antipsychotics demonstrate a better quality of life compared to those on antidepressants only? A comparative cross-sectional study of a nationally representative sample of the US population.

    Science.gov (United States)

    Al-Ruthia, Yazed Sulaiman; Hong, Song Hee; Solomon, David

    2015-01-01

    The adjunctive use of some atypical antipsychotics (AAPs) has been popular for patients with treatment-resistant depression. However, little is known about the impact of these agents on patients' Health-related quality of life (HRQoL). The objective of this study is to examine the impact of the adjunctive AAPs use on HRQoL among users of antidepressants with self-reported depression. Patients with depression (ICD-9-CM: 296, 300, and 311), and to have used the given AAPs and/or antidepressants for at least a year, were identified in the Medical Expenditure Panel Survey of 2008-2011. The patients were classified into users of adjunctive AAPs (i.e., antidepressants plus AAPs) and users of antidepressants only. Adjusted multivariate linear regression analyses were conducted to examine the association between the utilization of AAPs and HRQoL measure.(c) A total of 3638 participants who met the inclusion criteria were identified (306 on AAPs vs. 3332 on antidepressants only). The study subjects were ≥18 years, predominately White (91.9%) and female (71%). The AAPs utilization was not associated with higher scores in the Physical Component Summary (PCS-12) of the Short Form Health Survey (SF-12v2) (β = 1.542, 95% CI = -0.0142 to 3.0977, P = 0.0521). Rather, it was negatively associated with the Mental Component Summary (MCS-12) scores of the SF-12v2 (β = -1.5537, 95% CI = -3.0247 to -0.0827, P = 0.0385). The utilization of AAPs was not associated with higher scores of HRQoL. The findings of this study should underscore the need to consider other treatment options as add-on therapy for depression before resorting to AAPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters

    International Nuclear Information System (INIS)

    Singh, S.; Yamashita, A.; Gouaux, E.

    2007-01-01

    Sodium-coupled transporters are ubiquitous pumps that harness pre-existing sodium gradients to catalyse the thermodynamically unfavourable uptake of essential nutrients, neurotransmitters and inorganic ions across the lipid bilayer. Dysfunction of these integral membrane proteins has been implicated in glucose/galactose malabsorption, congenital hypothyroidism, Bartter's syndrome, epilepsy, depression, autism and obsessive-compulsive disorder. Sodium-coupled transporters are blocked by a number of therapeutically important compounds, including diuretics, anticonvulsants and antidepressants, many of which have also become indispensable tools in biochemical experiments designed to probe antagonist binding sites and to elucidate transport mechanisms. Steady-state kinetic data have revealed that both competitive and noncompetitive modes of inhibition exist. Antagonist dissociation experiments on the serotonin transporter (SERT) have also unveiled the existence of a low-affinity allosteric site that slows the dissociation of inhibitors from a separate high-affinity site. Despite these strides, atomic-level insights into inhibitor action have remained elusive. Here we screen a panel of molecules for their ability to inhibit LeuT, a prokaryotic homologue of mammalian neurotransmitter sodium symporters, and show that the tricyclic antidepressant (TCA) clomipramine noncompetitively inhibits substrate uptake. Cocrystal structures show that clomipramine, along with two other TCAs, binds in an extracellular-facing vestibule about 11 (angstrom) above the substrate and two sodium ions, apparently stabilizing the extracellular gate in a closed conformation. Off-rate assays establish that clomipramine reduces the rate at which leucine dissociates from LeuT and reinforce our contention that this TCA inhibits LeuT by slowing substrate release. Our results represent a molecular view into noncompetitive inhibition of a sodium-coupled transporter and define principles for the rational

  2. Anti-depressants make amphipods see the light.

    Science.gov (United States)

    Guler, Yasmin; Ford, Alex T

    2010-09-01

    The effects of serotonin altering parasites, serotonin, the anti-depressant fluoxetine, plus two other highly prescribed pharmaceuticals (carbamazepine and diclofenac) on the behaviour of the marine amphipod, Echinogammarus marinus were investigated. Acanthocephalan parasites are known to alter the swimming behaviour in their amphipod hosts through changes in serotonergic activity resulting in increased predation. Behavioural assays were adapted to record changes in phototaxis and geotaxis behaviour in male E. marinus following 7, 14 and 21 days exposure to serotonin and each pharmaceutical compound at 4 concentrations compared to a control (between 10 ng/L and 10 microg/L). E. marinus infected with acanthocephalans parasites had both significantly higher phototaxis and geotaxis scores than those of uninfected specimens. Phototaxis and geotaxis behaviour increased significantly in a concentration-dependent manner with exposure to serotonin. Fluoxetine significantly altered phototaxis and geotaxis activity in what appeared to be a non-monotonic concentration response curve with the greatest behavioural changes observed at 100 ng/L. The main patterns of these behavioural responses were consistent between two trials and the 3 weeks exposure with specimens spending more time within the light and occurring higher in the water column. No obvious trends could be concluded in the phototaxis and geotaxis scores from individuals exposed to carbamazepine or diclofenac as might be expected from their known mode of action. From this study phototaxis and geotaxis behaviour have been observed to be affected by exposure to serotonin modulators. Parasite studies have shown strong links between changes in behaviour and increased predation risk correlating with changes in serotonergic activity. This study has highlighted the potential for highly prescribed anti-depressant drugs to change the behaviour of an ecologically relevant marine species in ways which could conceivably lead to

  3. Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters

    Energy Technology Data Exchange (ETDEWEB)

    Singh,S.; Yamashita, A.; Gouaux, E.

    2007-01-01

    Sodium-coupled transporters are ubiquitous pumps that harness pre-existing sodium gradients to catalyse the thermodynamically unfavourable uptake of essential nutrients, neurotransmitters and inorganic ions across the lipid bilayer. Dysfunction of these integral membrane proteins has been implicated in glucose/galactose malabsorption, congenital hypothyroidism, Bartter's syndrome, epilepsy, depression, autism and obsessive-compulsive disorder. Sodium-coupled transporters are blocked by a number of therapeutically important compounds, including diuretics, anticonvulsants and antidepressants, many of which have also become indispensable tools in biochemical experiments designed to probe antagonist binding sites and to elucidate transport mechanisms. Steady-state kinetic data have revealed that both competitive and noncompetitive modes of inhibition exist. Antagonist dissociation experiments on the serotonin transporter (SERT) have also unveiled the existence of a low-affinity allosteric site that slows the dissociation of inhibitors from a separate high-affinity site. Despite these strides, atomic-level insights into inhibitor action have remained elusive. Here we screen a panel of molecules for their ability to inhibit LeuT, a prokaryotic homologue of mammalian neurotransmitter sodium symporters, and show that the tricyclic antidepressant (TCA) clomipramine noncompetitively inhibits substrate uptake. Cocrystal structures show that clomipramine, along with two other TCAs, binds in an extracellular-facing vestibule about 11 {angstrom} above the substrate and two sodium ions, apparently stabilizing the extracellular gate in a closed conformation. Off-rate assays establish that clomipramine reduces the rate at which leucine dissociates from LeuT and reinforce our contention that this TCA inhibits LeuT by slowing substrate release. Our results represent a molecular view into noncompetitive inhibition of a sodium-coupled transporter and define principles for the

  4. Agility: Agent - Ility Architecture

    National Research Council Canada - National Science Library

    Thompson, Craig

    2002-01-01

    ...., object and web technologies). The objective of the Agility project is to develop an open agent grid architecture populated with scalable, deployable, industrial strength agent grid components, targeting the theme 'agents for the masses...

  5. Mobile Agent Security

    National Research Council Canada - National Science Library

    Jansen, Wayne

    1998-01-01

    Mobile agent technology offers a new computing paradigm in which a program, in the form of a software agent, can suspend its execution on a host computer, transfer itself to another agent-enabled host...

  6. Interacting agents in finance

    NARCIS (Netherlands)

    Hommes, C.; Durlauf, S.N.; Blume, L.E.

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response

  7. Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models

    Science.gov (United States)

    Noordam, Raymond; Avery, Christy L; Visser, Loes E; Stricker, Bruno H

    2016-01-01

    Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., ‘treated-only design’, statistical power) and we will discuss how specifically drug–gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression. PMID:27248517

  8. Factors associated with the prescription of antidepressive medication to breast cancer patients

    DEFF Research Database (Denmark)

    Suppli, Nis P; Deltour, Isabelle; Damkjaer, Lars H

    2011-01-01

    We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants. Material and methods. We conducted a register-based cohort study of 1 247...... women with breast cancer diagnosed between 1998 and 2006 who attended a week-long rehabilitation program and a comparison group of 2 903 women who did not attend the program matched through the registers of the Danish Breast Cancer Cooperative Group. The associations between breast cancer......-related, treatment-related, and sociodemographic factors and use of antidepressants were evaluated in multivariate Cox proportional hazard models separated on use of antidepressants before diagnosis of breast cancer. Results. The mean follow-up for the 4 150 women in the study was 3.3 years (5-95% range, 0...

  9. Playing With Antidepressants: Perspectives From Indian Australians and Anglo-Australians Living With Depression.

    Science.gov (United States)

    Brijnath, Bianca; Antoniades, Josefine

    2017-11-01

    Patient perspectives were explored on the meaning and experience of antidepressant use by applying Johan Huizinga's theory of play to interviews from Indian Australians and Anglo-Australians diagnosed with depression. Through the analysis, the centrality of Huizinga's "magic circle" emerged, that is, defining the boundaries within which one could safely play. Consumption of antidepressants involved learning, breaking, and modulating rules of the game of adherence, then forging a new "magic circle." In these games, there were playful elements including experimentation, improvisation, absorption, and experiential learning. This application of Huizinga's theory in relation to antidepressant use is a novel approach in the literature on medication non/adherence. This application not only opens a new theoretical line of inquiry but also shows that antidepressant non/adherence is not a static practice but dynamic and changing, revealing critical insights around participant's agency, capabilities, desires, and notions of selfhood with regard to managing their depression and conceptualizing their recovery.

  10. Evolution of the concepts of the molecular mechanism of the action of antidepressants (survey)

    International Nuclear Information System (INIS)

    Mashkovskii, M.D.; Andreeva, N.I.

    1986-01-01

    The authors discuss investigation devoted to the study of the mechanisms of the action of antidepressants. Under the conditions of an acute experiment, antidepressants exhibit high affinity for the binding sites of [ 3 H] WB 4101, [ 3 H] LSD, and [ 3 H] spiroperiodol (alpha 1 - and S 2 -receptors). Certain antidepressants also have a high affinity for the binding sites of [ 3 H] clonidine and [ 3 H] S (alpha 2 - and S 1 -receptors). When the method of binding of radioligands was used to study the receptors, it was found that stimulation of cAMP synthesis, induced by norepinephrine, is primarily a beta-adrenergic response. Investigations of the influence of antidepressants in the case of their acute action in vitro on serotonin receptors showed that they inhibit the binding of [ 3 H] LSD and [ 3 H] spiroperiodol in the rat brain with high affinity and the binding of [ 3 H] S with low affinity

  11. Effect of antidepressants and neuroleptics on phosphoinositide turnover in human platelets

    International Nuclear Information System (INIS)

    Pandey, S.C.; Davis, J.M.; Schwertz, D.; Pandey, G.N.

    1990-01-01

    The authors previously reported that tricyclic antidepressants and iprindole inhibit thrombin-stimulated formation of inositol-1, 4 bisphosphate (IP2) and inositol-1,4,5 triphosphate (IP3) but do not cause any change in inositol-1 phosphate (IP1). In order to examine if this decrease in IP2 and IP3 formation by antidepressants is related to the inhibition of the enzyme phospholipase C (PLC), the authors determined the effects of antidepressants and neuroleptics on the levels of 3[H] phosphotidylinositol (PI), 3[H] PI-4 phosphate (PIP), 3[H] PI-4, 5 bisphosphate (PIP2) in human platelets. The implications of the findings and their relevance to the mode of action of antidepressants are discussed

  12. Patient risk profiles and practice variation in nonadherence to antidepressants, antihypertensives and oral hypoglycemics.

    NARCIS (Netherlands)

    Dijk, L. van; Heerdink, E.R.; Somai, D.; Dulmen, S. van; Sluijs, E.M.; Ridder, D.T. de; Griens, A.M.G.F.; Bensing, J.M.

    2007-01-01

    BACKGROUND: Many patients experience difficulties in following treatment recommendations. This study's objective is to identify nonadherence risk profiles regarding medication (antidepressants, antihypertensives, and oral hypoglycemics) from a combination of patients' socio-demographic

  13. Patient risk profiles and practice variation in nonadherence to antidepressants, antihypertensives and oral hypoglycemics

    NARCIS (Netherlands)

    Dijk, Liset van; Heerdink, E.R.; Somai, D.; Dulmen, S. van; Sluijs, E.M.; Ridder, D.T.D. de; Griens, A.M.G.F.; Bensing, J.

    2007-01-01

    Background: Many patients experience difficulties in following treatment recommendations. This study's objective is to identify nonadherence risk profiles regarding medication (antidepressants, antihypertensives, and oral hypoglycemics) from a combination of patients' socio-demographic

  14. Adherence to antidepressant medications: a randomized controlled trial of medication reminding in college students.

    Science.gov (United States)

    Hammonds, Tracy; Rickert, Krista; Goldstein, Carly; Gathright, Emily; Gilmore, Sarah; Derflinger, Bethany; Bennett, Brooke; Sterns, Anthony; Drew, Barbara L; Hughes, Joel W

    2015-01-01

    To determine if medication reminding via smartphone app increases adherence to antidepressant medications in college students. College students (N = 57) enrolled at a state-funded institution who had a current prescription for an antidepressant and regularly used a smartphone device. Participants were randomized to either a reminder group or a control group. Both groups were asked to complete a survey and undergo a manual pill count at the beginning of the study and 30 days later. There was a strong trend suggesting that the use of a medication reminder app was beneficial for adherence to antidepressant medication regimens. Factors influencing medication adherence in college students included health beliefs, use of illicit drugs, and type of professional care received. Use of a medication reminder may increase adherence to antidepressant medications in college students.

  15. The inhibition of phosphodiesterase type 5 as a novel target for antidepressant action

    DEFF Research Database (Denmark)

    Liebenberg, Nico

    2010-01-01

    therapy of depression. A recent study from our laboratory reported an antidepressant-like response in the rat forced swim test (FST) following chronic (11 day) co-administration of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the muscarinic acetylcholine (mACh) receptor antagonist atropine...... in Sprague Dawley rats. In the current study we explored the antidepressant-like properties of PDE5 inhibitors in Flinders Sensitive Line (FSL) rats, a genetic animal model of depression, and investigated the mechanism(s) that may be involved in the antidepressant-like activity of these drugs. We also......Major depression is one of the most debilitating diseases of our time, while current antidepressant treatments remain deficient in several ways. The nitric oxide (NO) / cyclic guanosine monophosphate (cGMP) / cGMP-dependent protein kinase (PK-G) pathway shows promise as a novel target for the drug...

  16. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk

    DEFF Research Database (Denmark)

    Borg, Linda; Julkunen, Anna; Madsen, Kristian Rørbaek

    2016-01-01

    It is often advised that patients who have ingested an overdose of antidepressants (AD) or antipsychotics (AP) are monitored with continuous ECG for minimum of 12-24 hr. These patients are often observed in an ICU. Our aim was to identify the number of patients with AD and/or AP overdose without...... adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need...... as antipsychotic overdose who would not require initial intensive care treatment. This is the first time the ADORA system has been evaluated in patients with antidepressant as well as antipsychotic overdose. This article is protected by copyright. All rights reserved....

  17. Linking Annual Prescription Volume of Antidepressants to Corresponding Web Search Query Data: A Possible Proxy for Medical Prescription Behavior?

    Science.gov (United States)

    Gahr, Maximilian; Uzelac, Zeljko; Zeiss, René; Connemann, Bernhard J; Lang, Dirk; Schönfeldt-Lecuona, Carlos

    2015-12-01

    Persons using the Internet to retrieve medical information generate large amounts of health-related data, which are increasingly used in modern health sciences. We analyzed the relation between annual prescription volumes (APVs) of several antidepressants with marketing approval in Germany and corresponding web search query data generated in Google to test whether web search query volume may be a proxy for medical prescription practice. We obtained APVs of several antidepressants related to corresponding prescriptions at the expense of the statutory health insurance in Germany from 2004 to 2013. Web search query data generated in Germany and related to defined search terms (active substance or brand name) were obtained with Google Trends. We calculated correlations (Person's r) between the APVs of each substance and the respective annual "search share" values; coefficients of determination (R) were computed to determine the amount of variability shared by the 2 variables. Significant and strong correlations between substance-specific APVs and corresponding annual query volumes were found for each substance during the observational interval: agomelatine (r = 0.968, R = 0.932, P = 0.01), bupropion (r = 0.962, R = 0.925, P = 0.01), citalopram (r = 0.970, R = 0.941, P = 0.01), escitalopram (r = 0.824, R = 0.682, P = 0.01), fluoxetine (r = 0.885, R = 0.783, P = 0.01), paroxetine (r = 0.801, R = 0.641, P = 0.01), and sertraline (r = 0.880, R = 0.689, P = 0.01). Although the used data did not allow to perform an analysis with a higher temporal resolution (quarters, months), our results suggest that web search query volume may be a proxy for corresponding prescription behavior. However, further studies analyzing other pharmacologic agents and prescription data that facilitate an increased temporal resolution are needed to confirm this hypothesis.

  18. Involvement of monoaminergic systems in anxiolytic and antidepressive activities of the standardized extract of Cocos nucifera L.

    Science.gov (United States)

    Lima, Eliane Brito Cortez; de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; E Silva Pereira, Yuri Freitas; Matos, Natália Castelo Branco; de Freitas, Rayanne Brito; Lima, Nycole Brito Cortez; Patrocínio, Manoel Cláudio Azevedo; Leal, Luzia Kalyne Almeida Moreira; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

    2017-01-01

    Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments. The forced swimming test was performed with dopaminergic and noradrenergic antagonists, as well as a serotonin release inhibitor. Administration of HECN in the FST after intraperitoneal (i.p.) pretreatment of mice with sulpiride (50 mg/kg), prazosin (1 mg/kg), or p-chlorophenylalanine (PCPA, 100 mg/kg) caused the actions of these three agents to be reversed. However, this effect was not observed after pretreating the animals with SCH23390 (15 µg/kg, i.p.) or yohimbine (1 mg/kg, i.p.) The dose chosen for HECN was 100 mg/kg, p.o., which increased the number of entries as well as the permanence in the open arms of the maze after acute and repeated doses. In both the forced swimming and the tail suspension tests, the same dose decreased the time spent immobile but did not disturb locomotor activity in an open-field test. The anxiolytic effect of HECN appears to be related to the GABAergic system, while its antidepressant effect depends upon its interaction with the serotoninergic, noradrenergic (α1 receptors), and dopaminergic (D2 dopamine receptors) systems.

  19. Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

    Science.gov (United States)

    Chee, K Y; Tripathi, A; Avasthi, A; Chong, M Y; Xiang, Y T; Sim, K; Kanba, S; He, Y L; Lee, M S; Chiu, H F K; Yang, S Y; Kuga, H; Udomratn, P; Tanra, A J; Maramis, M M; Grover, S; Mahendran, R; Kallivayalil, R A; Shen, W W; Shinfuku, N; Tan, C H; Sartorius, N

    2016-03-01

    Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

  20. Prenatal antidepressant exposure and risk of spontaneous abortion - a population-based study.

    Directory of Open Access Journals (Sweden)

    Maiken Ina Siegismund Kjaersgaard

    Full Text Available PURPOSE: To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy. METHODS: From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression. RESULTS: Of the 1,005,319 pregnancies (547,300 women identified, 114,721 (11.4% ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0% and 205 (11.1% ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI 1.10-1.18 for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80-1.24. No individual selective serotonin reuptake inhibitor (SSRI was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population. CONCLUSION: We identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual

  1. Prenatal antidepressant exposure and risk of spontaneous abortion - a population-based study.

    Science.gov (United States)

    Kjaersgaard, Maiken Ina Siegismund; Parner, Erik Thorlund; Vestergaard, Mogens; Sørensen, Merete Juul; Olsen, Jørn; Christensen, Jakob; Bech, Bodil Hammer; Pedersen, Lars Henning

    2013-01-01

    To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy. From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression. Of the 1,005,319 pregnancies (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and 205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10-1.18) for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80-1.24). No individual selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population. We identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual SSRI in particular were not associated with

  2. Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

    OpenAIRE

    Xie, Chen; Tang, Yurong; Wang, Yunfeng; Yu, Ting; Wang, Yun; Jiang, Liuqin; Lin, Lin

    2015-01-01

    Aim The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome. Methods We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis. Results Twelve randomized controlled trials were...

  3. Rave drug (ecstasy) and selective serotonin reuptake inhibitor anti-depressants.

    Science.gov (United States)

    Singh, A N; Catalan, J

    2000-04-01

    3, 4 Methylenedioxymethamphetamine (MDMA) also known as Ecstasy is a common recreational drug of abuse and reports of abuse of tricyclic antidepressants are also known. We report two cases of misuse of selective serotonin re-uptake inhibitors (SSRIs) antidepressants in combination with Ecstasy and their beneficial subjective effects experienced by misusers. We hypothesise the probable underlying pharmacological reasons and recommend its use in the treatment of neurotoxic effects of MDMA.

  4. Explaining geographic patterns of suicide in the US: the role of firearms and antidepressants

    OpenAIRE

    Opoliner, April; Azrael, Deborah; Barber, Catherine; Fitzmaurice, Garrett; Miller, Matthew

    2014-01-01

    Background: Suicide rates vary more than 3-fold across the fifty states. Previous ecological studies have pointed, separately, to covariation of suicide mortality with rates of a) household firearm ownership, and b) antidepressant prescriptions. Methods: An ecologic study using panel data from 2001-2005 was used to evaluate the joint and separate association of household firearm ownership and antidepressant prescription rates with the distribution of suicide rates across the United States. Ke...

  5. Prenatal Antidepressant Exposure and Risk of Spontaneous Abortion ? A Population-Based Study

    OpenAIRE

    Kjaersgaard, Maiken Ina Siegismund; Parner, Erik Thorlund; Vestergaard, Mogens; S?rensen, Merete Juul; Olsen, J?rn; Christensen, Jakob; Bech, Bodil Hammer; Pedersen, Lars Henning

    2013-01-01

    PURPOSE: To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy. METHODS: From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who we...

  6. Combined treatment with atypical antipsychotics and antidepressants in treatment-resistant depression: preclinical and clinical efficacy.

    Science.gov (United States)

    Rogóż, Zofia

    2013-01-01

    Several clinical reports have documented a beneficial effect of adding atypical antipsychotic drugs to ongoing treatments with antidepressants, particularly selective serotonin reuptake inhibitors, in ameliorating drug-resistant depression. The aim of this paper was to summarize some preclinical evidence describing the mechanism responsible for the therapeutic action of combined treatment with antidepressants and atypical antipsychotics and also some clinical data supporting the efficacy and safety of the augmentation strategy for improving antidepressant-resistant depression using atypical antipsychotics. This analysis is based on five microdialysis studies and nine behavioral studies assessing the impact of combined atypical antipsychotic and antidepressant treatments on extracellular levels of dopamine, serotonin and noradrenaline in the prefrontal cortex of freely moving rats and on antidepressant-induced effects, respectively. In addition, clinical data demonstrating the efficacy and safety of augmentation strategies for treatment-resistant depression using atypical antipsychotics were included. Combined treatment of rats with all studied atypical antipsychotics (olanzapine, risperidone, clozapine and quetiapine) and antidepressants (citalopram, fluoxetine and fluvoxamine) increased the extracellular level of dopamine in the prefrontal cortex compared to a respective drug given alone; in addition, a combination of olanzapine or quetiapine plus fluoxetine or fluvoxamine increased the levels of dopamine and noradrenaline. Moreover, atypical antipsychotics administered in a low dose enhanced the antidepressant-like activity of antidepressants, with (among other mechanisms) the serotonin 5-HT1A, 5-HT2A and adrenergic α2 receptors likely playing an important role in their action. The results support the conclusion that atypical antipsychotics may be effective as adjunctive therapy in treatment-resistant depression; however, their adverse effect profile may be

  7. RAVE DRUG (ECSTASY) AND SELECTIVE SEROTONIN REUPTAKE INHIBITOR ANTI-DEPRESSANTS

    OpenAIRE

    Singh, A.N.; Catalan, J.

    2000-01-01

    3, 4 Methylenedioxymethamphetamine (MDMA) also known as Ecstasy is a common recreational drug of abuse and reports of abuse of tricyclic antidepressants are also known. We report two cases of misuse of selective serotonin re-uptake inhibitors (SSRIs) antidepressants in combination with Ecstasy and their beneficial subjective effects experienced by misusers. We hypothesise the probable underlying pharmacological reasons and recommend its use in the treatment of neurotoxic effects of MDMA.

  8. Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

    Science.gov (United States)

    Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

    2014-01-01

    The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

  9. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    Science.gov (United States)

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  10. The Strategy of Combining Antidepressants in the Treatment of Major Depression: Clinical Experience in Spanish Outpatients

    Directory of Open Access Journals (Sweden)

    Luis M. Martín-López

    2011-01-01

    The most frequent combinations are SSRIs and tricyclic antidepressants. The active principle most widely combined is fluoxetine. Conclusions. The prevalence of use of antidepressant combination therapy is 2.2% of the global sample and 8.3% of treated patients. Other than duration of the depressive episode, no clinical characteristics exclusive to patients who received combination rather than monotherapy were found. Our study found that the most frequent combination is SSRIs + TCAs, also being the most studied.

  11. Attitudes and beliefs of patients with chronic depression toward antidepressants and depression

    Directory of Open Access Journals (Sweden)

    Jacob SA

    2015-05-01

    Full Text Available Sabrina Anne Jacob,1 Ab Fatah Ab Rahman,2 Mohamed Azmi Ahmad Hassali3 1School of Pharmacy, Monash University Malaysia, Sunway, 2Faculty of Health Sciences, Gong Badak Campus, Universiti Sultan Zainal Abidin (UniSZA, Kuala Terengganu, 3School of Pharmaceutical Sciences, University of Science Malaysia, Minden, Malaysia Background: Many patients have erroneous views with regard to depression and its management, and it was noted that these attitudes and beliefs significantly affected their adherence rates.Objectives: The primary aim of this study was to determine the attitudes and beliefs of patients with depression toward depression and antidepressants. A secondary aim was to assess the influence of ethnicity on patients’ attitudes and beliefs.Patients and methods: The study involved patients with chronic depression being followed up at an outpatient clinic at a government-run hospital in Malaysia. Patients’ attitudes and beliefs were assessed using the Antidepressant Compliance Questionnaire.Results: A total of 104 patients of Malay, Chinese, and Indian ethnic groups met the selection criteria. Chinese patients had significantly negative attitudes and beliefs toward depression and antidepressants compared to Malays and Indians (b=-8.96, t103=-3.22; P<0.05. Component analysis revealed that 59% of patients believed that antidepressants can cause a person to have less control over their thoughts and feelings, while 67% believed that antidepressants could alter one’s personality; 60% believed it was okay to take fewer tablets on days when they felt better, while 66% believed that antidepressants helped solve their emotional problems and helped them worry less.Conclusion: Patients had an overall positive view as to the benefits of antidepressants, but the majority had incorrect views as to the acceptable dosing of antidepressants and had concerns about the safety of the medication. Assessing patients’ attitudes and beliefs, as well as the

  12. The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review.

    Science.gov (United States)

    Kolla, Bhanu Prakash; Mansukhani, Meghna P; Bostwick, J Michael

    2018-04-01

    Restless legs syndrome is commonly co-morbid with medical conditions that are treated with antidepressant medications, such as depression, anxiety, fibromyalgia, and chronic insomnia disorder. Evidence from case reports and cross-sectional studies suggests that antidepressants may induce or worsen restless legs syndrome and increase periodic limb movements. We undertook a systematic review of the literature to identify and collate all prospective studies that measured restless legs syndrome symptoms and/or periodic limb movements following the introduction of an antidepressant. Eighteen studies were eligible for inclusion. Current data indicate that onset or exacerbation of restless legs syndrome and rise in frequency of periodic limb movements are uncommon following the initiation of an antidepressant. Among the various antidepressants, mirtazapine may be associated with higher rates of restless legs syndrome and periodic limb movements. One small study of normal volunteers suggested that venlafaxine may be associated with an increase in restless legs syndrome symptoms and periodic limb movements. Sertraline, fluoxetine, and amitriptyline appear to increase periodic limb movements that do not disrupt sleep and are thus unlikely to be clinically significant. On the other hand, bupropion may reduce restless legs syndrome symptoms, at least in the short term. Sedating antidepressants such as trazodone, nefazodone, and doxepin do not seem to aggravate periodic limb movements. The current evidence is limited by poor study design, inadequate use of standardized questionnaires, and heterogeneous populations studied for variable lengths of time. Future research should attempt to remedy these shortcomings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Reduced Treatment-Emergent Sexual Dysfunction as a Potential Target in the Development of New Antidepressants

    Directory of Open Access Journals (Sweden)

    David S. Baldwin

    2013-01-01

    Full Text Available Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered “ideal.” As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants.

  14. The role of mTOR in depression and antidepressant responses.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Neotti, Morgana V; Quevedo, João

    2014-04-17

    The aim of this study was to characterize the mTOR signaling cascade in depression and the actions that antidepressant drugs have on this pathway. Herein, a literature review was performed by verification and comparison of textbooks and journal articles that describe the characterization of the mTOR signaling cascade and its relationship to depression and antidepressant drugs, especially ketamine. Postmortem studies have shown robust deficits in the mammalian target of rapamycin (mTOR) signaling in the prefrontal cortex of subjects diagnosed with major depressive disorder. However, besides the mTOR signaling pathway having an antidepressant response to various drugs, this seems to be more associated with antidepressant N-methyl-d-aspartate (NMDA) receptor antagonists, such as ketamine. The characterization of the mTOR signaling pathway in depression and its action in response to antidepressants show great potential for the identification of new therapeutic targets for the development of antidepressant drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. "My dirty little habit": Patient constructions of antidepressant use and the 'crisis' of legitimacy.

    Science.gov (United States)

    Ridge, Damien; Kokanovic, Renata; Broom, Alex; Kirkpatrick, Susan; Anderson, Claire; Tanner, Claire

    2015-12-01

    Discontents surrounding depression are many, and include concerns about a creeping appropriation of everyday kinds of misery; divergent opinions on the diagnostic category(ies); and debates about causes and appropriate treatments. The somewhat mixed fortunes of antidepressants - including concerns about their efficacy, overuse and impacts on personhood - have contributed to a moral ambivalence around antidepressant use for people with mental health issues. Given this, we set out to critically examine how antidepressant users engage in the moral underpinnings of their use, especially how they ascribe legitimacy (or otherwise) to this usage. Using a modified constant comparative approach, we analyzed 107 narrative interviews (32 in UKa, 36 in UKb, 39 in Australia) collected in three research studies of experiences of depression in the UK (2003-4 UKa, and 2012 UKb) and in Australia (2010-11). We contend that with the precariousness of the legitimacy of the pharmaceutical treatment of depression, participants embark on their own legitimization work, often alone and while distressed. We posit that here, individuals with depression may be particularly susceptible to moral uncertainty about their illness and pharmaceutical interventions, including concerns about shameful antidepressant use and deviance (e.g. conceiving medication as pseudo-illicit). We conclude that while people's experiences of antidepressants (including successful treatments) involve challenges to illegitimacy narratives, it is difficult for participants to escape the influence of underlying moral concerns, and the legitimacy quandary powerfully shapes antidepressant use. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Antidepressants for depression in patients with dementia: a review of the literature.

    Science.gov (United States)

    Leong, Christine

    2014-04-01

    To evaluate the literature investigating the efficacy and safety of antidepressants for treating depression in individuals with dementia. A literature search was conducted using MEDLINE, PUBMED, EMBASE, and Cochrane databases from inception to May 2013 for studies in English that evaluated the treatment of depression in patients with dementia. All relevant randomized controlled trials (RCTs) and meta-analyses were identified using the search terms "dementia" or "Alzheimer's disease," and "depression" or "major depressive disorder." Reference lists from retrieved articles and practice guidelines were also searched for relevant literature. Only randomized, placebo-controlled trials and meta-analyses that compared an antidepressant with placebo for the treatment of depression in patients with dementia were included. In this systematic review, 10 RCTs and 3 meta-analyses were identified that examined the efficacy and safety of antidepressants compared with placebo in treating depression in patients with dementia. The majority of the RCTs consisted of a small sample size, and the antidepressants studied were not routinely used in practice. The evidence for antidepressants in the treatment of depression in patients with dementia is inconclusive. The accumulation of evidence suggests nonpharmacologic approaches and watchful waiting be attempted for the first 8 to 12 weeks in a patient who presents with both mild-to-moderate depression and dementia. In cases of severe depression, or depression not managed through nonpharmacologic means, a trial of an antidepressant may be initiated. However, further well-designed trials are needed to support these recommendations.

  17. Spinal dopaminergic involvement in the antihyperalgesic effect of antidepressants in a rat model of neuropathic pain.

    Science.gov (United States)

    Chen, Mi; Hoshino, Hajime; Saito, Shigeru; Yang, Yang; Obata, Hideaki

    2017-05-10

    Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we aimed to determine the involvement of the spinal dopaminergic system in the antihyperalgesic effects of antidepressants in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague-Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia. Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal thresholds after intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine. D2-like receptors were blocked by intrathecal administration of sulpiride. We also determined the concentrations of dopamine in the spinal cord using microdialysis after injection of antidepressants. The dopamine contents in the spinal dorsal horn were also measured in normal and SNL rats at 2, 3, 4, and 8 weeks after SNL surgery. Intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine (3-30mg/kg) produced antihyperalgesic effects, and prevented by intrathecal pre-injection of sulpiride (30μg). Microdialysis revealed the dopamine levels in the spinal cord were increased after intraperitoneal injection of each antidepressant (10mg/kg). Furthermore, the dopamine content in homogenized spinal cord tissue were increased at 2 weeks after SNL and then subsequently declined. Our results suggest that the effect of antidepressants against neuropathic pain is related to modulation of not only noradrenalin and serotonin but also dopamine levels in the spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Antidepressants for the treatment of depression in palliative care: systematic review and meta-analysis.

    Science.gov (United States)

    Rayner, Lauren; Price, Annabel; Evans, Alison; Valsraj, Koravangattu; Hotopf, Matthew; Higginson, Irene J

    2011-01-01

    Depression can exacerbate symptoms associated with life-threatening illness and increase disability and distress. In palliative care, depression occurs in a context of multiple symptoms, which complicates detection and treatment. While systematic reviews of antidepressants have been conducted in specific life-threatening diseases, no previous study has synthesized the evidence in palliative care. The objective of this study was to determine the efficacy of antidepressants for the treatment of depression in palliative care. MEDLINE, EMBASE, PSYCINFO and Cochrane trials registers were systematically searched to identify randomized controlled trials comparing antidepressants and placebo for the treatment of depression in palliative care. The primary outcome was efficacy assessed at three time-points. Twenty-five studies were included in the review. At each time-point antidepressants were more efficacious than placebo: 4-5 weeks odds ratio (OR) 1.93 (1.15-3.42) p = 0.001; 6-8 weeks OR 2.25 (1.38-3.67) p = 0.001; 9-18 weeks OR 2.71 (1.50-4.91) p = 0.001. This review provides evidence that antidepressants are effective in treating depression in palliative care. Their superiority over placebo is apparent within 4-5 weeks and increases with continued use. It is probable that the effect sizes yielded in this review overestimate the efficacy of antidepressants due to biases such as selective reporting and publication. Nevertheless, the magnitude and consistency of the effect suggests genuine benefit.

  19. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  20. The effect of anti-depressant and narcoleptic drugs on isopropyl iodoamphetamine biodistribution

    International Nuclear Information System (INIS)

    Moretti, J.L.; Holman, B.L.; Delmon, L.; Carmel, A.; Johnson, D.; Moingeon, P.; Blau, M.; Chu, H.

    1985-01-01

    I-123 Nisopropyl p-iodoamphetamine (IMP) is a useful radiotracer for imaging regional cerebral perfursion in a wide variety of neurological and cerebrovascular diseases. The major route of amine metabolism in the lung is the mixed function oxidase (MFO) system. A number of antidepressants and narcoleptic agents have been shown to displace amphetamine from the lung. If these drugs release IMP before it is metabolized to lipophobic products, brain concentration will be affected. The authors investigated the effects of these drugs on IMP distribution in animals with high and low pulmonary concentrations of MFO. When 1 mg/kg imipramine (IM) was injected iv into Wistar rats 30 min before IMP and 50 min before sacrifice, lung activity was depressed (4 + 1% ID vs 12 + 4% ID). Brain activity was depressed only with 4 mg/kg IM (l.5 + .3% ID vs 2.7 + .7% ID). There was no significant difference in IMP brain activity without IM and when IM was given simultaneously with, 5 or 15 min after IMP. In New Zealand rabbits which have a low pulmonary MFO concentration, IM altered lung and brain uptake during simultaneous injection and as late as 15 min after IMP. Lung uptake was reduced 51% and brain uptake was increased 25%, 20%, and 19% when IM was injected 0, 5 and 15 min after IMP. The MAO inhibitors, phenelzine and L deprenyl, did not alter the brain, lung or liver IMP activity in rats at a dose of 5 mg/kg. These data are consistent with a model in which IMP is trapped and metabolized in the lung by the MFO system. Assuming an active MFO system in the human (unlike the rabbit), brain activity of IMP will not be altered by either IM or MAO inhibitors

  1. Steric hindrance mutagenesis in the conserved extracellular vestibule impedes allosteric binding of antidepressants to the serotonin transporter

    DEFF Research Database (Denmark)

    Plenge, Per; Shi, Lei; Beuming, Thijs

    2012-01-01

    The serotonin transporter (SERT) controls synaptic serotonin levels and is the primary target for antidepressants, including selective serotonin reuptake inhibitors (e.g. (S)-citalopram) and tricyclic antidepressants (e.g. clomipramine). In addition to a high affinity binding site, SERT possesses...... a low affinity allosteric site for antidepressants. Binding to the allosteric site impedes dissociation of antidepressants from the high affinity site, which may enhance antidepressant efficacy. Here we employ an induced fit docking/molecular dynamics protocol to identify the residues that may...... effects of Zn(2+) binding in an engineered site and the covalent attachment of benzocaine-methanethiosulfonate to a cysteine introduced in the extracellular vestibule. The data provide a mechanistic explanation for the allosteric action of antidepressants at SERT and suggest that the role of the vestibule...

  2. L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

    Science.gov (United States)

    Xue, Jinsong; Li, Hongyan; Deng, Xueyang; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

    2015-07-01

    L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

    Science.gov (United States)

    Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

    2016-01-26

    In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Use of antidepressants during pregnancy and the risk of spontaneous abortion.

    Science.gov (United States)

    Nakhai-Pour, Hamid Reza; Broy, Perrine; Bérard, Anick

    2010-07-13

    The risk of relapse of depression or the diagnosis of some other psychiatric disorders during pregnancy necessitates the use of antidepressants despite possible adverse effects. Whether such use increases the risk of spontaneous abortion is still being debated. We evaluated the risk of spontaneous abortion in relation to the use of antidepressants during pregnancy. Using a nested case-control study design, we obtained data from the Quebec Pregnancy Registry for 5124 women who had a clinically detected spontaneous abortion. For each case, we randomly selected 10 controls from the remaining women in the registry who were matched by the case's index date (date of spontaneous abortion) and gestational age at the time of spontaneous abortion. Use of antidepressants was defined by filled prescriptions and was compared with nonuse. We also studied the classes, types and doses of antidepressants. A total of 284 (5.5%) of the women who had a spontaneous abortion had at least one prescription for an antidepressant filled during the pregnancy, as compared with 1401 (2.7%) of the matched controls (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.83-2.38). After adjustment for potential confounders, we found that the use of antidepressants during pregnancy was associated with an increased risk of spontaneous abortion (OR 1.68, 95%CI 1.38-2.06). Stratified analyses showed that use of selective serotonin reuptake inhibitors alone (OR 1.61, 95% CI 1.28-2.04), serotonin-norepinephrine reuptake inhibitors alone (OR 2.11, 95% CI 1.34-3.30) and combined use of antidepressants from different classes (OR 3.51, 95% CI 2.20-5.61) were associated with an increased risk of spontaneous abortion. When we looked at antidepressant use by type versus no use, paroxetine use alone (OR 1.75, 95% CI 1.31-2.34) and venlafaxine use alone (OR 2.11, 95% CI 1.34-3.30) were associated with an increased risk of spontaneous abortion. The use of antidepressants, especially paroxetine, venlafaxine or the

  5. Antidepressants during pregnancy and autism in offspring: population based cohort study.

    Science.gov (United States)

    Rai, Dheeraj; Lee, Brian K; Dalman, Christina; Newschaffer, Craig; Lewis, Glyn; Magnusson, Cecilia

    2017-07-19

    Objectives  To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring. Design  Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison. Setting  Stockholm County, Sweden. Participants  254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records. Main outcome measure  Offspring diagnosis of autism spectrum disorder, with and without intellectual disability. Results  Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability. Conclusions  The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the

  6. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    OpenAIRE

    Go Taniguchi; Miho Miyajima; Masako Watanabe; Yoshiko Murata; Daichi Sone; Yutaka Watanabe; Mitsutoshi Okazaki; Motonori Kobayashi-Kimura; Masaaki Kato; Teiichi Onuma

    2015-01-01

    Classic antidepressants have been known to induce convulsive seizures and nonconvulsive status epilepticus (NCSE). On the other hand, many reports have emphasized the safety of novel antidepressants. However, we encountered three cases of NCSE in the elderly associated with the use of newer antidepressants at therapeutic doses. All three patients were male and were 73?years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. I...

  7. Psychosocial work environment and antidepressant medication: a prospective cohort study

    DEFF Research Database (Denmark)

    Bonde, Jens Peter; Munch-Hansen, T.; Wieclaw, J.

    2009-01-01

    BACKGROUND: Adverse psychosocial work environments may lead to impaired mental health, but it is still a matter of conjecture if demonstrated associations are causal or biased. We aimed at verifying whether poor psychosocial working climate is related to increase of redeemed subscription of antid......BACKGROUND: Adverse psychosocial work environments may lead to impaired mental health, but it is still a matter of conjecture if demonstrated associations are causal or biased. We aimed at verifying whether poor psychosocial working climate is related to increase of redeemed subscription......: The proportion of employees that received at least one prescription of ADs from 1995 through 2006 was 11.9% and prescriptions rose steadily from 1.50% in 1996 to the highest level 6.47% in 2006. ADs were prescribed more frequent among women, middle aged, employees with low occupational status and those living...... alone. None of the measured psychosocial work environment factors were consistently related to prescription of antidepressant drugs during the follow-up period. CONCLUSION: The study does not indicate that a poor psychosocial work environment among public service employees is related to prescription...

  8. The radioimmunoassay of clomipramine (Anafranil-Geigy): a tricyclic antidepressant

    International Nuclear Information System (INIS)

    Read, G.F.; Riad-Fahmy, D.

    1977-01-01

    A radioimmunoassay has been developed for the tricyclic antidepressant, clomipramine (Anafranil-Geigy) which allows accurate determination of plasma levels without a pr-assay purification step. This is achieved by generation of specific antisera using an antigen produced by conjugation of clomipramine to bovine serum albumin via the 10,11 bridge positions. As expected cross reaction of the pharmacologically active major metabolite, desmethylclomipramine was 5% and that of didesmethyclomipramine 1%. Specificity was confirmed by comparing titres achieved in the routine assay with those observed in an assay incorporating a pre-assay thin layer chromatographic purification step. Pharmacokinetic data were in agreement with double radioisotope derivative assays and also with previously reported assays using G.C. or G.C./M.S. techniques. The sensitivity is superior to any previous assay known to us for this class of compound. The specificity and precision, coupled with the high sample turnover (greater than 300 samples/week per technician) make the assay ideal for supervision of patient compliance and routine assay of samples generated in large clinical trials. (orig.) [de

  9. A psychogenic dystonia perfect responsive to antidepressant treatment.

    Directory of Open Access Journals (Sweden)

    Volkan Solmaz

    2014-03-01

    Full Text Available After ruling out of organic causes, movement disorders are named as psychogenic movement disorders, it can mimic perfectly Organic movement disorders, but with a good history, clinical observations and detailed examination is very helpful in the diagnosis of this disease. In here we will present a 15 years old male patient, he was complaining of urinary incontinence at night, emerging dystonic posture especially in crowded environments, eating, and during activities that require attention, for 5 years. Self and family history was unremarkable. His physical and neurological examination was normal except for dystonic posture esipecially writing and when doing skilled jobs. All the tests were normal for the differential diagnosis. Taking into account the patient\\s clinical findings and cilinical test, the patient was diagnosed as psychogenic dystonia. He gave a very good response to treatment with antidepressants and psychotherapy. As a result, in clinical practice both the diagnostic and therapeutic challenges the psychogenic movement disorders is an important problem, and to get rid of the negative effects of unnecessary diagnostic test and side efects of treatment, you need to keep in mind this diagnosis. [J Contemp Med 2014; 4(1.000: 29-31

  10. Antidepressants share the ability to increase catecholamine output in the bed nucleus of stria terminalis: a possible role in antidepressant therapy?

    Science.gov (United States)

    Cadeddu, Roberto; Ibba, Marcello; Sadile, Adolfo; Carboni, Ezio

    2014-05-01

    Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria teminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. The aim of this study, carried out by means of in vivo microdialysis, was to ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST. We observed that all the antidepressants tested (5-20 mg/kg i.p.) increased the output of catecholamines, dose dependently. In particular, the maximum increases (as a percent of basal) for norepinephrine and dopamine respectively, were as follows: desipramine, 239 and 137; reboxetine, 185 and 128; imipramine, 512 and 359; citalopram, 95 and 122; fluoxetine, 122 and 68; bupropion, 255 and 164. These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders.

  11. Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.

    Directory of Open Access Journals (Sweden)

    Anna V Zetterqvist

    Full Text Available BACKGROUND: The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. METHODOLOGY: We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1 extent of violative advertising; (2 pattern of code breaches; (3 rate at which the system reacted to violative advertising; (4 prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5 costs for manufactures associated with violative advertising. PRINCIPAL FINDINGS: Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34% advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. CONCLUSIONS: Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across

  12. Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.

    Science.gov (United States)

    Zetterqvist, Anna V; Mulinari, Shai

    2013-01-01

    The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self-regulatory settings, and if appropriate measures are not taken to

  13. Misleading Advertising for Antidepressants in Sweden: A Failure of Pharmaceutical Industry Self-Regulation

    Science.gov (United States)

    Zetterqvist, Anna V.; Mulinari, Shai

    2013-01-01

    Background The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. Methodology We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994–2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Principal Findings Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Conclusions Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system’s failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self

  14. Use of anti-depressants and the risk of fracture of the hip or femur.

    Science.gov (United States)

    van den Brand, M W M; Pouwels, S; Samson, M M; van Staa, T P; Thio, B; Cooper, C; Leufkens, H G M; Egberts, A C G; Verhaar, H J J; de Vries, F

    2009-10-01

    Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

  15. Explaining geographic patterns of suicide in the US: the role of firearms and antidepressants.

    Science.gov (United States)

    Opoliner, April; Azrael, Deborah; Barber, Catherine; Fitzmaurice, Garrett; Miller, Matthew

    2014-12-01

    Suicide rates vary more than 3-fold across the fifty states. Previous ecological studies have pointed, separately, to covariation of suicide mortality with rates of a) household firearm ownership, and b) antidepressant prescriptions. An ecologic study using panel data from 2001-2005 was used to evaluate the joint and separate association of household firearm ownership and antidepressant prescription rates with the distribution of suicide rates across the United States. Key exposures were household firearm ownership prevalence (using data from the 2004 Behavioral Risk Factor Surveillance System) and antidepressant prescription rates (using data supplied by IMS health). Negative binomial mixed-effect models were used to estimate the association between household firearm ownership prevalence and antidepressant prescriptions rates and state level suicide rates (using data from the National Vital Statistics System), overall and by method of suicide (firearm vs. non-firearm). Sensitivity analyses examined analogous county-level data for those counties for which firearm ownership measures were available. All analyses were adjusted for median income, unemployment rate, and percent of population in urban areas. In adjusted analyses, household firearm prevalence is significantly associated with overall suicide rates (adjusted incidence rate ratio (IRRa) = 1.28, 95% confidence interval (CI): 1.18, 1.38) and firearm suicides rates (IRRa = 1.61, CI: 1.45, 1.80), but not with non-firearm suicide rates (IRRa = 1.05, 95% CI: 0.95, 1.16). By contrast, adjusted analyses find no relationship between suicide rates and antidepressant prescription rates. Findings from county-level analyses were consistent with state-level results. The prevalence of household firearm ownership is strongly and significantly associated with overall suicide rates, due to its association with firearm suicide rates. This association is robust to consideration of the role of antidepressant

  16. High H1-affinity antidepressants and risk of metabolic syndrome in bipolar disorder.

    Science.gov (United States)

    Salvi, Virginio; Barone-Adesi, Francesco; D'Ambrosio, Virginia; Albert, Umberto; Maina, Giuseppe

    2016-01-01

    Metabolic syndrome (MetS) is common in patients with bipolar disorder, with a relative risk of 1.6-2 compared to the general population. The increased risk is believed to be due to unhealthy lifestyles and use of medications. Although antipsychotics and mood stabilizers have been associated with weight gain and MetS, the impact of antidepressants has not been comprehensively evaluated. The objective of the study is to assess the risk of MetS in patients exposed to different types of antidepressants. In this cross-sectional study, 294 patients with bipolar disorder were consecutively recruited. MetS was diagnosed according to NCEP ATP-III modified criteria. Antidepressants used by the patients were classified according to the usual nomenclature (SSRI, TCA, SNRI, and other antidepressants) and a pharmacodynamic classification taking into account histamine 1-receptor (H1-R) affinity. Use of antidepressants in general was not associated with MetS (prevalence ratio [PR], 1.08; 95% confidence interval, 0.73 to 1.62; p = 0.70). However, subjects using H1-R high-affinity antidepressants (N = 15) showed a substantial increase in the prevalence of MetS (PR, 2.17; 95 % confidence interval, 1.24 to 3.80; p = 0.007). When we included the inhibition constant (Ki) as a continuous covariate in the models, we found an inverse association between Ki and prevalence of MetS (p = 0.004). We observed for the first time in a clinical setting that a pharmacodynamic-based classification of antidepressants could be more useful than the traditional one to predict the risk of MetS in patients with bipolar disorder. Clinical consequences may be relevant. However larger studies are warranted to generalize these results.

  17. REM sleep homeostasis in the absence of REM sleep: Effects of antidepressants.

    Science.gov (United States)

    McCarthy, Andrew; Wafford, Keith; Shanks, Elaine; Ligocki, Marcin; Edgar, Dale M; Dijk, Derk-Jan

    2016-09-01

    Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 h of REM-sleep specific restriction through EEG-triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by paroxetine and citalopram were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Use of antidepressants and association with elective termination of pregnancy: population based case-control study.

    Science.gov (United States)

    Kieler, H; Malm, H; Artama, M; Engeland, A; Furu, K; Gissler, M; Nørgaard, M; Stephansson, O; Valdimarsdottir, U; Zoega, H; Haglund, B

    2015-11-01

    To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy. Case-control study using data from national registers. Denmark, Finland, and Norway during the period 1996-2007. A total of 14,902 women were included as cases and 148,929 women were included as controls. Cases were women with elective termination of pregnancy at 12-23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors. Association between antidepressant use during pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage. At least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0-2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies. The use of any type of antidepressants was associated with elective termination of pregnancy at 12-23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies. © 2014 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

  19. Antidepressants and risk of cataract development: A population-based, nested case-control study.

    Science.gov (United States)

    Chou, Po-Han; Chu, Che-Sheng; Chen, Yi-Huei; Hsu, Min-Yen; Huang, Min-Wei; Lan, Tsuo-Hung; Lin, Ching-Heng

    2017-06-01

    Previous studies demonstrated increased risk of cataract development among users of selective serotonin reuptake inhibito