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Sample records for antidepressants

  1. Antidepressants

    Science.gov (United States)

    Antidepressants are medicines that treat depression. Your doctor can prescribe them for you. They work to balance ... them to help. There are several types of antidepressants. You and your doctor may have to try ...

  2. Combining antidepressants

    OpenAIRE

    Dunner, David L.

    2014-01-01

    Summary Treatment-resistant depression is a common problem encountered by psychiatrists. These patients are often difficult to treat effectively. Strategies for addressing patients with treatment-resistant depression include changing medications, adding another antidepressant (antidepressant polypharmacy), and augmenting treatment with a non-antidepressant.

  3. 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.

  4. [Antidepressives and antidepressive interactions with other drugs].

    Science.gov (United States)

    Zavrsnik, Davorka; Spirtović, Selma; Becić, Fahir

    2006-01-01

    During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge. The aim of this work is to point out the possible interactions between antidepressive agents and other drugs. PMID:16425539

  5. IC Treatment: Antidepressants

    Science.gov (United States)

    ... in Combined Federal Campaign ICA Resources for Donors Social Media ... you first hear the name antidepressant you may think of a medicine used to treat depression. Did you know that antidepressants are also effective ...

  6. Antidepressants and dementia

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Søndergård, Lars; Forman, Julie Lyng; Andersen, Per Kragh

    2009-01-01

    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......-SSRI antidepressants and older antidepressants). All findings were replicated in sub-analyses with Alzheimer's disease as outcome. LIMITATIONS: Methodological reasons for the findings cannot be excluded due to the non-randomized nature of data. CONCLUSIONS: Continued long-term antidepressant treatment was associated...

  7. Antidepressants and dementia

    DEFF Research Database (Denmark)

    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...

  8. Treating Depression: Should You Consider an Antidepressant?

    Science.gov (United States)

    Treating Depression: Should You Consider An Antidepressant? What are antidepressants? Antidepressants are drugs used to treat the symptoms of depression. Do I need an antidepressant? You probably do not ...

  9. Antipsychotics as antidepressants.

    Science.gov (United States)

    Roberts, Rona Jeannie; Lohano, Kavita K; El-Mallakh, Rif S

    2016-09-01

    Three second-generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone. PMID:25963405

  10. 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

  11. 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.

  12. Antidepressant Induced Mania : Is it a risk factor for Antidepressant Abuse?

    OpenAIRE

    Ramesh, S; Khandelwal, Sudhir K

    2003-01-01

    Induction of mania is a common occurrence with antidepressant use. A case of antidepressant induced hypomania leading to antidepressant abuse is presented. The clinical implications of antidepressant abuse in bipolar disorder are discussed.

  13. Adherence to Antidepressant Medication

    OpenAIRE

    Åkerblad, Ann-Charlotte

    2007-01-01

    Non-adherence to medication is a major obstacle in the treatment of depression. The objectives of the present study were to explore the effect of two interventions aiming to increase antidepressant treatment adherence, and to examine long-term consequences and costs of depression in adherent and non-adherent primary care patients. A randomised controlled design was used to assess the respective effects of a written educational adherence enhancing programme and therapeutic drug monitoring in ...

  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. [Antidepressant drugs and breastfeeding].

    Science.gov (United States)

    Bellantuono, Cesario; Migliarese, Giovanni; Maggioni, Francesca; Imperadore, Giuseppe

    2007-01-01

    The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect. PMID:17345878

  16. Breastfeeding and Antidepressants

    OpenAIRE

    Field, Tiffany

    2008-01-01

    Although a large literature supports the benefits of breastfeeding, this review suggests that breastfeeding is less common among postpartum depressed women, even though their infants benefit from the breastfeeding. Depressed mothers, in part, do not breastfeed because of their concern about potentially negative effects of antidepressants on their infants. Although sertraline (Zoloft) and paroxetine (Paxol) concentrations are not detectable in infants’ sera, fluoxetine (Prozac) and citalopram ...

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

    OpenAIRE

    Zoltan Rihmer; Xenia Gonda

    2011-01-01

    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 (hypo)manic switches, mixed depressive episode, and antidepressant-associated suicidality among d...

  18. Tricyclic antidepressant radioreceptor assay

    International Nuclear Information System (INIS)

    A receptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [3H]-3-guinuclidnyl benzilate (3H-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.)

  19. Antidepressant medications and osteoporosis

    DEFF Research Database (Denmark)

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

    2012-01-01

    types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk......, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive...... for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment...

  20. The Successful Use of Antidepressants

    OpenAIRE

    Eppel, Alan B.

    1989-01-01

    Depression is the most common psychiatric problem presenting to the family physician. The prevalence of depression among family-practice patients is of the order of 10%. Most cases of depression are treated by family physicians. Thus it is essential for family physicians to be fully familiar with the effective use of antidepressants. This article outlines the key components necessary for the successful use of antidepressants. The author discusses appropriate indications, dosage, length of tre...

  1. Neuroimmune endocrine effects of antidepressants

    OpenAIRE

    Antonioli M; Rybka J; Carvalho LA

    2012-01-01

    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...

  2. Pharmacogenetics of antidepressants

    Directory of Open Access Journals (Sweden)

    Concetta eCrisafulli

    2011-02-01

    Full Text Available Up to 60% of depressed patients do not respond completely to antidepressants (AD and up to 30% do not respond at all. Genetic factors contribute for about 50% of the AD response. During the recent years the possible influence of a set of candidate genes as genetic predictors of AD response efficacy was investigated by us and others. They include the cytochrome P450 (CYP superfamily, the P-glycoprotein (ABCB1, the tryptophan hydroxylase (TPH, the catechol-O-methyltransferase (COMT, the monoamine oxidase A (MAOA, the serotonin transporter (5-HTTLPR, the norepinephrine transporter (NET, the dopamine transporter (DAT, variants in the 5HT1A, 2A , 3A, 3B and 6 receptors, adrenoreceptor beta-1 (ADRB1 and alpha-2 (ADRA2A, the dopamine receptors (D2, the G-protein beta3-subunit (GNB3, the corticotropin releasing hormone (CRH receptors (CRHR1 and CRHR2, the glucocorticoid receptors (GR, the c-AMP response-element binding (CREB and the brain-derived neurotrophic factor (BDNF. Marginal associations were reported for angiotensin I converting enzyme (ACE, circadian locomoter output cycles kaput protein (CLOCK, glutamatergic system, nitric oxide synthase (NOS and interleukin 1-beta (IL-1beta gene. In conclusion, gene variants seem to influence human behavior, liability to disorders and treatment response. Nonetheless, gene x enviroment interactions have been hypothesized to modulate several of these effects.

  3. Antidepressant chronotherapeutics for bipolar depression.

    Science.gov (United States)

    Benedetti, Francesco

    2012-12-01

    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or "orphan" treatment to a powerful clinical instrument in everyday psychiatric practice. PMID:23393416

  4. 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.

  5. [Prospective evaluation of antidepressant discontinuation].

    Science.gov (United States)

    Mourad, I; Lejoyeux, M; Adès, J

    1998-01-01

    The authors prospectively assessed symptoms induced by the interruption of antidepressants in 16 patients (11 women and 5 men), aged from 33 to 85 years (mean = 52.4 +/- 16.4), treated with antidepressants since at least two weeks. All patients were free of alcohol abuse or dependence disorder and of other dependence to psychoactive substances. None of them presented medical illness. Diagnosis were made by separate evaluations by two authors and confirmed with a semistructered assessment instrument: the Schedule for Affective Disorders and Schizophrenia (Lifetime Version). All patients were submitted to a brutal discontinuation of their antidepressant agent. Patients were assessed twice, before the interruption of the antidepressant, and 72 hours later. Effects of antidepressant interruption were assessed by several means. Modification of anxiety and depression were evaluated using the Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale. Symptoms of withdrawal were assessed with Cassano and al.'s scale SESSH including an evaluation of anxiety, agitation, irritability, anergy, difficulty on concentrating, depersonalization, sleep and appetite disorders, muscle pains, nausea, tremor, sweating, altered taste, hyperosmia, paresthesias, photophobia, motor incoordination, dizziness, hyperacousia pain, delirium. Fourteen of the 16 patients (87.5%) presented modifications of their somatic or psychic state 3 days after the interruption of the antidepressant treatment. Most frequent symptoms were: increase in anxiety (31%), increase in irritability (25%), sleep disorders (19%), decrease of anergia and fatigue (19%). Mean scores of anxiety and depression were not significantly modified by the withdrawal. Following TCAs interruption (7 patients) most frequent symptoms were sleep disorders; increase in anxiety, nausea. Among patients withdrawn from SSRIs (6 patients), most frequent symptoms were increase in anxiety, increase in irritability

  6. [Driving fitness in therapy with antidepressive drugs].

    Science.gov (United States)

    Soyka, M; Dittert, S; Gartenmeier, A; Schäfer, M

    1998-04-01

    The driving ability of patients under therapy with antidepressives is seen less restrictive than some years ago. The inhibition of psychomotor performance is of special interest. Some empirical studies point at antidepressives increasing the risk for accidents at least in elderly patients. Different groups of antidepressants apparently show different effects. Tricyclic antidepressants were shown to worsen cognitive and psychomotor performance in some patients while serotonin reuptake inhibitors and some other new antidepressants may cause less behavioral toxicity. Methodological problems in assessing driving ability and some recent findings are discussed. PMID:9587241

  7. [Switching and combining strategies of antidepressant medications].

    Science.gov (United States)

    Charpeaud, Thomas; Moliere, Fanny; Bubrovszky, Maxime; Haesebaert, Frédéric; Allaïli, Najib; Bation, Rémy; Nieto, Isabel; Richieri, Raphaëlle; Saba, Ghassen; Bellivier, Frank; Bennabi, Djamila; Holtzmann, Jérôme; Camus, Vincent; Courtet, Philippe; Courvoisier, Pierre; d'Amato, Thierry; Doumy, Olivier; Garnier, Marion; Bougerol, Thierry; Lançon, Christophe; Haffen, Emmanuel; Leboyer, Marion; Llorca, Pierre-Michel; Vaiva, Guillaume; El-Hage, Wissam; Aouizerate, Bruno

    2016-03-01

    Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects. PMID:26995511

  8. 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. PMID

  9. Antidepressant chronotherapeutics for bipolar depression

    OpenAIRE

    Benedetti, Francesco

    2012-01-01

    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in di...

  10. Running is rewarding and antidepressive

    OpenAIRE

    Brené, Stefan; Bjørnebekk, Astrid; Åberg, Elin; Mathé, Aleksander A.; Olson, Lars; Werme, Martin

    2007-01-01

    Natural behaviors such as eating, drinking, reproduction and exercise activate brain reward pathways and consequently the individual engages in these behaviors to receive the reward. However, drugs of abuse are even more potent to activate the reward pathways. Rewarding behaviors and addictive drugs also affect other parts of the brain not directly involved in the mediation of reward. For instance, running increases neurogenesis in hippocampus and is beneficial as an antidepressant in a genet...

  11. VGF, a New Player in Antidepressant Action?

    OpenAIRE

    Malberg, Jessica E.; Monteggia, Lisa M.

    2008-01-01

    Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepressant treatments, is important for the development of more potent and specific treatments of depression. There is growing evidence that growth factors may be important mediators of...

  12. Sleep deprivation and antidepressant treatment

    OpenAIRE

    Voderholzer, Ulrich

    2003-01-01

    The mood-improving effect of sleep deprivation (SD) in depression is even today still not fully understood. Despite the fact that mood and cognitive functions are lowered by prolonged sleep loss and despite convincing data that insomnia is a strong risk factor for subsequent depression, 1 acute SD for one night or even partial SD in the second half of the night improves mood in about 60% of depressed patients the day after. 2,3 In this respect, among alt types of antidepressant treatments, SD...

  13. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

    , 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....

  14. 21 CFR 862.3910 - Tricyclic antidepressant drugs test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs...

  15. 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...

  16. Antidepressants in social anxiety disorder

    Directory of Open Access Journals (Sweden)

    Nardi Antonio E.

    2001-01-01

    Full Text Available Social anxiety disorder (SAD is a marked and persistent fear of doing almost everything in front of people due to concerns about being judge by others. An up-to-date review is needed in order to reach a practical judgement of all psychopharmacological data. Case reports, open and double-blind trials with SAD were described and commented upon from a clinical point of view. The MEDLINE system was searched from 1975 to 2001. The references from the selected papers were also used as a source. MAOIs (fenelzine, tranylcypromine, reversible monoamino oxidase-A inhibitors (moclobemide, brofaromine, SSRIs (paroxetine, sertraline, fluoxetine, fluvoxamine and some other antidepressants (venlafaxine, nefazodone have proven effective in several studies with various methodologies. The MAOIs have more serious adverse effects and the SSRIs have the best tolerance. SSRIs are efficacious and the first choice of treatment.

  17. Provide optimized antidepressant monotherapy with multiple drugs before considering antidepressant polypharmacy

    OpenAIRE

    SAAH, Tammy; Garlow, Steven J.; Rapaport, Mark H.

    2014-01-01

    Summary Many patients with chronic or recurring major depressive disorder have suboptimal responses to the wide range of antidepressant medications available. When confronted with these patients, clinicians may augment the original antidepressant with other medications, including adjunctive treatment with a second or third antidepressant. Although it is a widely-used practice among psychiatrists and primary care physicians in high-income countries, evidence for the benefits of this type of an...

  18. 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

  19. Extracorporeal treatment for tricyclic antidepressant poisoning

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  20. 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

  1. Disparities in antidepressant use in pregnancy

    OpenAIRE

    Yamamoto, Ayae; McCormick, Marie C.; Burris, Heather H.

    2014-01-01

    Background: The American College of Obstetricians and Gynecologists and the American Psychiatric Association both recommend pharmacotherapy for perinatal depression when the benefits outweigh the risks. While minority adults are less likely to use antidepressant medications compared to Non-Hispanic Whites, whether this pattern occurs among pregnant women is unclear. Objective: We sought to determine the frequency of antidepressant medication use reported during ambulatory care visits for preg...

  2. Suicide and Antidepressants: What Current Evidence Indicates

    OpenAIRE

    Anil Nischal; Adarsh Tripathi; Anuradha Nischal; Trivedi, J.K.

    2012-01-01

    The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, it is assumed that antidepressants are beneficial for all symptoms of depression, including suicidality. However, some evidence suggests that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of suicidal ideas in vulnera...

  3. Antidepressants modulate glycine action in rat hippocampus

    OpenAIRE

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-01-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, we...

  4. Effects of BDNF Polymorphisms on Antidepressant Action

    OpenAIRE

    Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

    2010-01-01

    Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidep...

  5. Antidepressant prescribing in five European countries

    DEFF Research Database (Denmark)

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

    2014-01-01

    PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalen......-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations....

  6. 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.

  7. 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

  8. Talk Therapy May Help Depressed Teens Who Shun Antidepressants

    Science.gov (United States)

    ... Talk Therapy May Help Depressed Teens Who Shun Antidepressants Cognitive behavioral therapy can help boost mood without ... 20, 2016 (HealthDay News) -- Depressed teens who refuse antidepressants may benefit from counseling, a new study suggests. ...

  9. Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects

    Science.gov (United States)

    ... html Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects Data from 8 randomized clinical trials suggests ... fish oil supplements may improve the effectiveness of antidepressants, new research suggests. Researchers reviewed the findings of ...

  10. Exposure / Ritual Prevention Therapy Boosts Antidepressant Treatment of OCD

    Science.gov (United States)

    ... NIMH (99 items) Exposure / Ritual Prevention Therapy Boosts Antidepressant Treatment of OCD CBT Trumps Antipsychotic for Augmentation, ... Update A form of behavioral therapy can augment antidepressant treatment of obsessive compulsive disorder (OCD) better than ...

  11. Antidepressant No Help to Heart Failure Patients: Study

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159604.html Antidepressant No Help to Heart Failure Patients: Study Depression ... 2016 TUESDAY, June 28, 2016 (HealthDay News) -- The antidepressant Lexapro may not help heart failure patients suffering ...

  12. Drug treatment episodes in pharmacoepidemiology - antidepressant use as a model

    NARCIS (Netherlands)

    Gardarsdottir, H.

    2009-01-01

    In the Netherlands, antidepressants are indicated for treating depression, generalized anxiety disorders, obsessive-compulsive disorders, social phobia, panic disorders, eating disorders, neuropathic pain and nocturnal enuresis. In addition, antidepressants are sometimes used for treating off-label

  13. Clinical application of antidepressants in the treatment of insomnia symptoms

    Directory of Open Access Journals (Sweden)

    WONG Iok-man

    2013-11-01

    Full Text Available Insomnia is one of the common complaints among all clinical departments. In recent years, some studies have demonstrated that insomnia symptoms can be improved or treated by some antidepressants. Based on literature search both at home and abroad, this paper summarized the effect of various antidepressants with different pharmacological properties on sleep, and the progress of clinical application of antidepressants in treating insomnia according to the classification of antidepressant drugs.

  14. Antidepressants modulate glycine action in rat hippocampus.

    Science.gov (United States)

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-12-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current. PMID:26730381

  15. 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.

  16. 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.

  17. GPs motivations of prescribing antidepressants and their practical relevance.

    NARCIS (Netherlands)

    Volkers, A.; Jong, A. de; Braspenning, J.C.C.; Bakker, D. de; Dijk, L. van

    2004-01-01

    Background: Insight in the motivations of prescribing antidepressants may contribute to advance the efficiency of the current, large antidepressant prescription rate. Less is known about why general practitioners (GPs) treat patients with antidepressants or not and choose modern SSRIs instead of the

  18. Antidepressant Prescription and Suicide Rates: Effect of Age and Gender

    Science.gov (United States)

    Kalmar, Sandor; Szanto, Katalin; Rihmer, Zoltan; Mazumdar, Sati; Harrison, Katrin; Mann, J. John

    2008-01-01

    To determine whether the effect of antidepressant exposure on suicide rate is modified by age and gender in Hungary, annual antidepressant prescription rates and suicide rates of about 10 million inhabitants between 1999-2005 were analyzed by age and gender groups. The suicide rate was inversely related to the increased use of antidepressants in…

  19. 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 of...

  20. [Therapy of dementia with antipsychotics and antidepressives].

    Science.gov (United States)

    Frölich, L; Hausner, L

    2015-04-01

    In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724

  1. Tritiation of unsaturated tricyclic antidepressants for radioimmunoassay

    International Nuclear Information System (INIS)

    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

  2. Synthesis of the Commercial Antidepressant Moclobemide

    Science.gov (United States)

    More, Jesse D.

    2008-01-01

    An experiment for the undergraduate organic chemistry laboratory is described in which students synthesize the commercial antidepressant drug moclobemide, marketed under the trade name Manerix. This one-step synthesis starts from commercially available material and produces moclobemide in high yield. The product is initially isolated as its…

  3. Suicidality and aggression during antidepressant treatment

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  4. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

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

    2005-01-01

    neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4-5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment...

  5. The multiple outcomes bias in antidepressants research.

    Science.gov (United States)

    Procopio, Marco

    2005-01-01

    Despite the widespread use of antidepressant medication, there are no signs that the burden of depression and suicide is decreasing in the industrialised world. This is generating mounting scepticism on the effectiveness of this class of drugs as an approach for the treatment of mood disorders. These doubts are also fuelled by the increasing awareness that the literature on antidepressants is fundamentally flawed and under the control of the pharmaceutical companies. This article describes systematically for the first time what is probably the most insidious and misleading of the biases that affect this area of research: the "multiple outcomes bias". Most trials on the effectiveness of antidepressants, instead of first establishing a hypothesis and then trying to demonstrate it, following the scientific method, start instead "data mining", without a clear hypothesis, and then select for publication, amongst a multitude of outcomes, only the ones that favour the antidepressant drug, ignoring the others. This method has obviously no scientific validity and is very misleading, allowing the manipulation of the data without any overt fraudulent action. There is the need to generate new research, independently funded and with clear hypotheses established "a priori ". What is at stake is not only the appraisal of the balance between benefits and potential damage to the patients when using this class of medications, after the realisation that they are not as harmless as believed. It is also to establish whether the research on antidepressant medication has gone on a "wild goose chase" over the last half century, concentrating almost exclusively on molecules that modify the monoaminergic transmission at synaptic level and virtually ignoring any other avenue. PMID:15922120

  6. 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.

  7. [Neuroleptic malignant syndrome from treatment with antidepressives].

    Science.gov (United States)

    Heinemann, F; Assion, H J; Laux, G

    1997-05-01

    The neuroleptic malignant syndrome (NMS) is a rare complication in the treatment of neuroleptics. The pathophysiology is not fully known. A dopaminergic transmission block in the basal ganglia and the hypothalamus is thought to be the pathophysiological mechanism of NMS. There are some findings against the single role of dopamine receptor blockade: NMS is rare under neuroleptic treatment, although a strong dopamine receptor blockade is found even with a low dosis of neuroleptics. NMS can develop even after longterm treatment with neuroleptics and is not improved by dopamine agonists within the expected period. NMS may even develop when neuroleptics are reduced. Several cases have been reported of NMS precipitated by medication without a direct effect on dopaminergic system. Only rare case reports describe NMS under antidepressants. We report on all cases of NMS associated with antidepressants and present the different pathophysiological hypotheses on the precipitation of NMS. PMID:9235312

  8. Treatment of anorexia nervosa with antidepressants.

    Science.gov (United States)

    Hudson, J I; Pope, H G; Jonas, J M; Yurgelun-Todd, D

    1985-02-01

    Nine patients with anorexia nervosa were treated with antidepressant medications from three classes: tricyclics, monoamine oxidase inhibitors, and triazolopyridines. A tenth patient was treated with the combination of lithium carbonate and carbamazepine. With either the initial or a subsequent medication trial, four patients had displayed significant improvement in weight and in other anorexic and bulimic symptoms. Three additional patients had a marked or moderate improvement in bulimic symptoms, one with moderate and two without any weight gain. Two other patients had moderate weight gain. Side effects were a significant problem in many of the patients. These preliminary results suggest that antidepressants may be of benefit in the treatment of some patients with anorexia nervosa. PMID:3919068

  9. Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

    OpenAIRE

    Hanson, Nicola D; Owens, Michael J.; Nemeroff, Charles B.

    2011-01-01

    The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summa...

  10. Antidepressant drugs: evaluation of price variation

    Directory of Open Access Journals (Sweden)

    Bhumika Jayantilal Patel

    2015-06-01

    Conclusion: Price variation was wide for antidepressant drugs. Generic drug prescribing can decrease the expenditure of patient on the drug. Prescribers should be provided updated knowledge of the cost of different drugs. Modifications in pharmaceutical policy are required, and prices of the drug should be controlled in effective way for all the drugs. [Int J Basic Clin Pharmacol 2015; 4(3.000: 432-437

  11. Antidepressant activity of fingolimod in mice

    OpenAIRE

    di Nuzzo, Luigi; Orlando, Rosamaria; Tognoli, Cristina; Di Pietro, Paola; Bertini, Giuseppe; Miele, Jessica; Bucci, Domenico; Motolese, Marta; Scaccianoce, Sergio; Caruso, Alessandra; Mauro, Gianluca; De Lucia, Carmine; Battaglia, Giuseppe; Bruno, Valeria; Fabene, Paolo Francesco

    2015-01-01

    Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed ...

  12. ANTI-DEPRESSANT POTENTIAL OF GHIYA

    Directory of Open Access Journals (Sweden)

    Kaur Satbir

    2012-04-01

    Full Text Available Lagenaria siceraria (Cucurbitaceae, popularly known as bottle gourd, lauki or ghiya, is a climbing plant, which bears hard-shelled and bottle-shaped gourds as fruits. Ghiya forms an excellent diet for people having digestive problems being rich in vitamins, iron and minerals. Since, it contains low calories, bottle gourd is an awesome foodstuff for shedding extra calories. The fruit possesses diuretic, emetic, and refrigerant properties. The ghiya (lauki juice is helpful in constipation, premature graying hair, urinary disorders and insomnia. However, there are no reports in literature pertaining to CNS actions of Lagenaria siceraria fruit. In the light of above, the present study was undertaken to test the anti-depressant potential of Lagenaria siceraria juice (LSJ. Lagenaria siceraria juice was administered at various concentrations ranging from 4%-16% v/v orally to Swiss mice (30g, once daily for 15 successive days. The anti-depressant activity was measured using Forced Swim Test (FST and Tail Suspension Test (TST. The efficacy of Lagenaria siceraria was compared to standard anti-depressant drugs viz: fluoxetine (20mg/kg, p.o, imipramine (15mg/kg, p.o and phenelzine (20 mg/kg, p.o. Lagenaria siceraria significantly reduced the immobility time of mice in both FST and TST. Prazosin, Baclofen, Sulpiride and p-CPA significantly antagonized this reduction in immobility duration. Furthermore, Lagenaria siceraria juice inhibited the monoamine oxidase (MAO enzyme and reduced significantly malondialdehyde (MDA levels. These findings reveal the anti-depressant potential of ghiya.

  13. Antidepressants and psychotherapy: a clinical research review

    OpenAIRE

    Frank, Ellen; Novick, Danielle; Kupfer, David J.

    2005-01-01

    This review focuses on information concerning antidepressants and psychotherapy in the treatement of both acute and chronic forms of unipolar depression in the English language literature. In it, we address the use of combination therapy, both from the outset of treatment and in a variety of sequences, ie, we examine the potential advantages of adding a targeted psychotherapy to an incompletely effective pharmacotherapy and the potential advantages of adding pharmacotherapy to an incompletely...

  14. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    OpenAIRE

    Shahin Akhondzadeh; Javad Maleki

    2007-01-01

    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 i...

  15. Suicide and antidepressants: What current evidence indicates

    Directory of Open Access Journals (Sweden)

    Anil Nischal

    2012-01-01

    Full Text Available The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, it is assumed that antidepressants are beneficial for all symptoms of depression, including suicidality. However, some evidence suggests that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of suicidal ideas in vulnerable patients. Systematic reviews and pooled analysis of experimental, observational, and epidemiological studies have investigated the use of SSRIs and their association with suicidality. Taking account of the methodological limitations of these studies, the current evidence fails to provide a clear relationship between their use and risk of suicidality in adults. However, in children and adolescents, there appears to be a bit of increased risk of suicidal ideations and attempts, but not of completed suicides. This risk can be anticipated and managed clinically. Clinicians are, therefore, advised to maintain a close follow-up during the initial treatment periods and remain vigilant of this risk. This advisory, however, should not deter clinicians from the use of effective dosages of antidepressants for a sufficient period of time, in every age group of patients, when clinically needed, and if found suitable otherwise.

  16. 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.

  17. 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.

  18. Antidepressant use during pregnancy and asthma in the offspring

    DEFF Research Database (Denmark)

    Liu, Xiaoqin; Olsen, Jørn; Pedersen, Lars Henning; Agerbo, Esben; Yuan, Wei; Li, Jiong

    2015-01-01

    regression model, we estimated the hazard ratio (HR) for asthma in the offspring after antidepressant use during pregnancy. RESULTS: Of the 733 685 children identified, 84 683 had a diagnosis of asthma. A total of 21 371 children were exposed to prenatal maternal depression (ie, a diagnosis of depressive...... prenatal depression and no antidepressant use during pregnancy, the HR for asthma after any antidepressant use during pregnancy was 1.00 (95% CI: 0.93–1.08). HRs after use of selective serotonin reuptake inhibitors only, newer antidepressants only, and older antidepressants only were 0.95 (95% CI: 0......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...

  19. 13C NMR studies of the molecular flexibility of antidepressants

    International Nuclear Information System (INIS)

    The solution dynamics of a series of clinically potent antidepressants have been investigated by measuring 13C 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

  20. Voluntary Exercise Produces Antidepressant and Anxiolytic Behavioral Effects in Mice

    OpenAIRE

    Duman, Catharine H.; Schlesinger, Lee; Russell, David S.; Duman, Ronald S

    2008-01-01

    Reports of beneficial effects of exercise on psychological health in humans are increasingly supported by basic research studies. Exercise is hypothesized to regulate antidepressant-related mechanisms and we therefore characterized the effects of chronic exercise in mouse behavioral paradigms relevant to antidepressant actions. Mice given free access to running wheels showed antidepressant-like behavior in learned helplessness, forced-swim (FST) and tail suspension paradigms. These responses ...

  1. Antidepressant mechanism of ketamine: perspective from preclinical studies

    OpenAIRE

    Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Chuang, De-Maw

    2015-01-01

    A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine's rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, ps...

  2. Paroxetine versus other anti-depressive agents for depression

    OpenAIRE

    Cipriani, Andrea; Furukawa, Toshi A.; Veronese, Antonio; Watanabe, Norio; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

    2007-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of major depressive disorder.To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents.

  3. Drug treatment episodes in pharmacoepidemiology - antidepressant use as a model

    OpenAIRE

    Gardarsdottir, H.

    2009-01-01

    In the Netherlands, antidepressants are indicated for treating depression, generalized anxiety disorders, obsessive-compulsive disorders, social phobia, panic disorders, eating disorders, neuropathic pain and nocturnal enuresis. In addition, antidepressants are sometimes used for treating off-label indications such as sleeping disorders, urinary incontinence and headache. The diversity in the nature of these conditions results in a variety of antidepressant treatment patterns. The common use ...

  4. Sertraline versus other antidepressive agents for depression

    Science.gov (United States)

    Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

    2014-01-01

    Background The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. Objectives To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either

  5. 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

    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...... 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 Udgivelsesdato: 2009...

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

    DEFF Research Database (Denmark)

    Bech, P

    2010-01-01

    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...

  7. Antidepressant Effects of Ginsenosides from Panax notoginseng

    Institute of Scientific and Technical Information of China (English)

    YAO Yang; SANG Wei; YANG Xiu-shi; ZHAI Mei-jing; WANG Li-li; QIN Pei-you; WU Li; ZHOU Xian-rong; WANG Li-jun; ZHU Zhi-hua; REN Gui-xing

    2012-01-01

    Ginsenosides Rg1,Rb1,R1,Rd,and Re are major constituents of Panax notoginseng,a famous traditional Chinese medicinal herb,which has both stimulative and inhibitory effects on the central nervous system (CNS).The monoamine hypothesis proposes that depression is a result of the depletion of 5-hydroxytryptamine (5-HT),norepinephrine (NE) and dopamine (DA) in addition to the activation of monoamine oxidase in the CNS.The purpose of this study was to determine whether P.notoginseng Saponin (PNS) has an antidepressant activity.We investigated the antidepressant-like activities of Rg1,Rb1,R1,Rd,and Re in mice,using two animal models of depression.In addition,we analyzed the neurochemicals by the chronic unpredictable mild stress test.Our results showed that Rb 1,Rd,and Re treatment at 10 mg kg-1 significantly reduced the duration of immobility in both the tail suspension and forced swimming tests.Rb1,Rd,and Re increases in 5HT and NE levels at 10 mg kg-1 in both the frontal cortex and hippocampus.Dopamine levels increased in the hippocampus and the striatum.Moreover,5-hydroxyindoleacetic acid (5-HIAA) levels were found increased in the hippocampus.These findings suggest that the antidepressant effects of Rb1,Rd,and Re may be related to the increase in 5-HT and NE in the CNS,and through the alterations in the synthesis or metabolism of dopamine.

  8. Antidepressants and testicular cancer: cause versus association.

    Science.gov (United States)

    Andrade, Chittaranjan

    2014-03-01

    A data mining study that examined associations between 105 drugs and 55 cancer sites found significant associations between 2 selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and testicular cancer. The study suggested several reasons why these associations merited further investigation. A later study tested specific relationships between 12 antidepressant drugs and testicular cancer and subtypes thereof; whereas significant relationships were again found, these disappeared after adjusting for confounding variables. These 2 studies are educative because they illustrate how false-positive results can easily arise in exploratory research and how confounding may be responsible for statistically significant relationships in study designs that are not randomized controlled trials. PMID:24717391

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

    NARCIS (Netherlands)

    Korf, J

    1996-01-01

    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 b

  10. Antidepressants and lethal violence in the Netherlands 1994-2008

    NARCIS (Netherlands)

    P.F. Bouvy (Paul); M. Liem (Marieke)

    2012-01-01

    textabstractRationale There is an ongoing discussion on the relation between risk of violent behaviour and the use of antidepressants. The claim that the use of antidepressants can cause violent behaviour would gain credibility if a positive association between the two could be established. Objectiv

  11. 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 antidepre

  12. 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...

  13. Review of Evidence for Use of Antidepressants in Bipolar Depression

    OpenAIRE

    McInerney, Shane J.; Kennedy, Sidney H.

    2014-01-01

    Objective: Depressive episodes predominate over the course of bipolar disorder and cause considerable functional impairment. Antidepressants are frequently prescribed in the treatment of bipolar depression, despite concerns about efficacy and risk of switching to mania. This review provides a critical examination of the evidence for and against the use of antidepressants in bipolar depression.

  14. Potential involvement of serotonergic signaling in ketamine's antidepressant actions

    DEFF Research Database (Denmark)

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina;

    2016-01-01

    A single i.v. infusion of ketamine, classified as an N-methyl-D-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic...... properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5......-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms...

  15. Exposure to antidepressants during pregnancy--prevalences and outcomes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen

    2014-01-01

    still conflicting. The main challenge is how to discern between the effects of the drug and the effect of the depression itself. We approached this dire problem conducting a nation-wide register based study analyzing the relation between use of antidepressants during pregnancy and the risk of congenital...... malformations and perinatal mortality. We performed our analysis with focus on women pausing treatment before pregnancy to account for special characteristics associated with women redeeming a prescription for an antidepressant. Furthermore, we reported prevalences of antidepressant use, in Denmark, in relation...... in utero to an antidepressant in any of the three trimesters. The overall conclusion is that antidepressants are not associated with increased risks of congenital malformations and perinatal mortality. However, we cannot rule out a possible causal relation, and treatment must therefore be based on an...

  16. Evaluation of antidepressant activity of tramadol in mice

    Directory of Open Access Journals (Sweden)

    Tayal Vandana

    2008-01-01

    Full Text Available Objective: To evaluate antidepressant like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10,20 and 40 mg/kg,i.p once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug treated mice were recorded in tail suspension test (TST.The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p, administered for seven days. Results: Tramadol produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control. The efficacy of tramadol at doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10 mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. Conclusion: The results of the present study indicate antidepressant like activity of tramadol.

  17. The unfulfilled promise of the antidepressant medications.

    Science.gov (United States)

    Davey, Christopher G; Chanen, Andrew M

    2016-05-16

    Australia has one of the highest rates of antidepressant use in the world; it has more than doubled since 2000, despite evidence showing that the effectiveness of these medications is lower than previously thought. An increasing placebo response rate is a key reason for falling effectiveness, with the gap between response to medications and placebo narrowing. Psychotherapies are effective treatments, but recent evidence from high-quality studies suggests that their effectiveness is also modest. Combined treatment with medication and psychotherapy provides greater effectiveness than either alone. The number of patients receiving psychotherapy had been declining, although this trend is probably reversing with the Medicare Better Access to Mental Health Care initiative. Antidepressant medications still have an important role in the treatment of moderate to severe depression; they should be provided as part of an overall treatment plan that includes psychotherapy and lifestyle strategies to improve diet and increase exercise. When medications are prescribed, they should be used in a way that maximises their chance of effectiveness. PMID:27169968

  18. 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

  19. 5HT3 receptors: Target for new antidepressant drugs.

    Science.gov (United States)

    Gupta, Deepali; Prabhakar, Visakh; Radhakrishnan, Mahesh

    2016-05-01

    5HT3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists. 5HT3Rs located on the serotonergic and other neurotransmitter interneuronal projections control their release and affect mood and emotional behavior; however, new evidence suggests that apart from modulating the neurotransmitter functions, 5HT3R antagonists have protective effects in the pathogenic events including hypothalamic-pituitary-adrenal-axis hyperactivity, brain oxidative stress and impaired neuronal plasticity, pointing to hereby unknown and novel mechanisms of their antidepressant action. Nonetheless, further investigations are warranted to establish the exact role of 5HT3Rs in depression and antidepressant action of 5HT3R antagonists. PMID:26976353

  20. 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

  1. 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. PMID:22461754

  2. 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

  3. Study Questions Use of Antidepressants for Children, Teens

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159262.html Study Questions Use of Antidepressants for Children, Teens They ... interpersonal therapy -- as the first-line treatment," said study author Dr. Andrea Cipriani. He is an associate ...

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

    International Nuclear Information System (INIS)

    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 ([3H]WB4101, [3H]QNB, [3H]d-LSD, [3H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [3H]mepyramine, [3H]d-LSD and [3H]WB4101 while it was very weak on [3H]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 [3H]DHA binding, [3H]spiroperidol binding, [3H]flunitrazepam binding, [3H]muscimol binding and [3H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed. (Auth.)

  5. Antidepressants and local anesthetics: drug interactions of interest to dentistry

    Directory of Open Access Journals (Sweden)

    Lea Rosa Chioca

    2010-10-01

    Full Text Available Introduction: Since there is a vast variety of pharmacological treatments for mental conditions, it has been increasingly more common that patients seeking dentistry treatment are continually using psychoactive drugs as antidepressants. The number of people taking antidepressants is increasing; consequently, dentists should update their knowledge on the interaction between this drug class and those used in dental daily practice, such as local anesthetics and vasoconstrictors. Objective: To conduct a literature review on this subject. Literature review and conclusion: Literature data suggest that sympathomimetic vasoconstrictors (epinephrine, norepinephrine, and phenylephrine associated with local anesthetics may potentiate the side effects of antidepressants, particularly tricyclics and MAO inhibitors, on the cardiovascular system. There are few clinical trials and preclinical studies on this subject, and most of them were carried out between the 60s and 80s. Current studies are needed, since many new antidepressant drugs with different mechanisms of action are currently marketed and being used.

  6. 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 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...... survivors were at increased risk of having antidepressants prescribed (HR, 1.4; 95% confidence interval (CI), 1.3-1.5). The excess absolute risk of antidepressant use was 2.5 per 1000 person-years (95% CI, 1.7-3.3), equivalent to an excess of 2.5 survivors for every 100 survivors followed for 10years...

  7. Interaction of tricyclic antidepressants with cholestyramine in vitro.

    Science.gov (United States)

    Bailey, D N; Coffee, J J; Anderson, B; Manoguerra, A S

    1992-08-01

    The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants. PMID:1519310

  8. Study Finds No Heart Risk from SSRI Antidepressants

    Science.gov (United States)

    ... Study Finds No Heart Risk From SSRI Antidepressants Prozac actually appeared to protect against heart attack, researchers ... analysis suggests. Commonly prescribed SSRIs include Celexa, Lexapro, Prozac, Paxil and Zoloft. The findings are reassuring, said ...

  9. Study Questions Use of Antidepressants for Children, Teens

    Science.gov (United States)

    ... analysis suggests. Of the 14 antidepressants studied, only fluoxetine (Prozac) was more effective in treating depression than an ... teens aged 13 to 18, the researchers noted. "Prozac should be considered only for patients who do ...

  10. EMSAM (deprenyl patch): how a promising antidepressant was underutilized

    OpenAIRE

    Asnis GM; Henderson MA

    2014-01-01

    Gregory M Asnis,1,2 Margaret A Henderson2 1Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY, USA; 2Anxiety and Depression Clinic, Montefiore Medical Center, New York, NY, USA Abstract: The EMSAM patch is a unique monoamine oxidase inhibitor (MAOI) being the only antidepressant utilizing a transdermal delivery system. This was welcomed by clinicians who hoped that EMSAM would be better tolerated than oral MAOIs and non-MAOI antidepressants, a...

  11. Antidepressants-Associated Sexual Dysfunction: Impact, Effects and Treatment

    OpenAIRE

    HIGGINS, AGNES; LYNCH, AILEEN MARIA; Nash, Michael

    2010-01-01

    PUBLISHED Sexual dysfunction is a common side effect of antidepressants and can have significant impact on the person?s quality of life, relationships, mental health, and recovery. The reported incidence of sexual dysfunction associated with antidepressant medication varies considerably between studies, making it difficult to estimate the exact incidence or prevalence. The sexual problems reported range from decreased sexual desire, decreased sexual excitement, diminished or...

  12. Antidepressant exposure during early pregnancy and congenital malformations

    DEFF Research Database (Denmark)

    Pedersen, Lars Henning

    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......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...

  13. Antidepressant Use During Pregnancy: Current Controversies and Treatment Strategies

    OpenAIRE

    PAYNE, JENNIFER L; Meltzer-Brody, Samantha

    2009-01-01

    The treatment of depression during pregnancy is both a common and complex clinical challenge. The decision to expose the fetus to antidepressant medication during pregnancy must be weighed against the risks of untreated maternal depression to both mother and fetus. Maternal depression during pregnancy has been associated with increased rates of preterm birth and maternal substance use. The safety of antidepressant use during pregnancy appears to be largely reassuring but there remain two area...

  14. Location of the Antidepressant Binding Site in the Serotonin Transporter IMPORTANCE OF SER-438 IN RECOGNITION OF CITALOPRAM AND TRICYCLIC ANTIDEPRESSANTS

    DEFF Research Database (Denmark)

    Andersen, Jacob; Taboureau, Olivier; Hansen, Kasper B.;

    2009-01-01

    antidepressants, including the selective serotonin reuptake inhibitor citalopram and the tricyclic antidepressants imipramine, clomipramine, and amitriptyline. A conservative mutation of Ser-438 to threonine (S438T) selectively increased the K-i values for these antidepressants up to 175-fold. The effects of...

  15. 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.

  16. Antidepressant Treatment for Acute Bipolar Depression: An Update

    Science.gov (United States)

    Amit, Ben H.; Weizman, Abraham

    2012-01-01

    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. PMID:22319648

  17. 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. PMID:26407778

  18. Antidepressants and inflammatory bowel disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Andrews Jane M

    2006-09-01

    Full Text Available Abstract Background A number of studies have suggested a link between the patient's psyche and the course of inflammatory bowel disease (IBD. Although pharmacotherapy with antidepressants has not been widely explored, some investigators have proposed that treating psychological co-morbidities with antidepressants may help to control disease activity. To date a systematic analysis of the available studies assessing the efficacy of antidepressants for the control of somatic symptoms in IBD patients has not been performed. Methods We searched electronic databases, without any language restriction. All relevant papers issued after 1990 were examined. Results 12 relevant publications were identified. All of them referred to non-randomised studies. Antidepressants reported in these publications included paroxetine, bupropion, amitriptyline, phenelzine, and mirtazapine. In 10 articles, paroxetine, bupropion, and phenelzine were suggested to be effective for treating both psychological and somatic symptoms in patients suffering from IBD. Amitriptyline was found ineffective for treating somatic symptoms of IBD. Mirtazapine was not recommended for IBD patients. Conclusion Although most of reviewed papers suggest a beneficial effect of treatment with antidepressants in patients with IBD, due to the lack of reliable data, it is impossible to judge the efficacy of antidepressants in IBD. Properly designed trials are justified and needed based upon the available uncontrolled data.

  19. Meta-analysis of the antidepressant response to sleep deprivation and its correlates: towards a better antidepressant therapy

    OpenAIRE

    Pollock, Michael

    2010-01-01

    Unlike antidepressant drugs, which typically require several weeks to produce an antidepressant response, sleep deprivation produces a response literally overnight. Quantification (meta-analysis) of 166 articles, including data from a total of 3951 depressed patients, reveals that consistently half of all depressed patients are responders to a night of sleep deprivation, with the degree of response shown by these responders being on average a 55% decrease in depression levels. While the level...

  20. 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.

  1. Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

    Science.gov (United States)

    Nguyen, Linda; Matsumoto, Rae R

    2015-12-15

    Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. PMID:25804358

  2. 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.

  3. An algorithm to identify antidepressant users with a diagnosis of depression from prescription data.

    NARCIS (Netherlands)

    Gardarsdottir, H.; Egberts, T.C.G.; Dijk, L. van; Sturkenboom, M.; Heerdink, E.R.

    2008-01-01

    Background: Investigating depression treatment outcomes in prescription databases is problematic when information on indication for antidepressant prescriptions is unavailable. Objectives: To develop and validate an algorithm using prescription data to identify antidepressant drug users who suffer f

  4. Seasonal patterns of initiating antidepressant therapy in general practice in the Netherlands during 2002-2007.

    NARCIS (Netherlands)

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

    2010-01-01

    Background: Studies on seasonality in antidepressant prescribing showed prescribing peaks during autumn and winter. Since then, new antidepressants have become available and indications have broadened, possibly contributing to a change inprescribing practices. This study investigates seasonal patter

  5. Antidepressant Use in Persons Aged 12 and Over: United States, 2005-2008

    Science.gov (United States)

    ... Order from the National Technical Information Service NCHS Antidepressant Use in Persons Aged 12 and Over: United ... in 10 Americans aged 12 and over takes antidepressant medication. 1 Significantly different from age group 18– ...

  6. 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.......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....

  7. Prescribing patterns of antidepressants in Europe: results from the Factors Influencing Depression Endpoints Research (FINDER) study

    OpenAIRE

    Bauer, Michael; Monz, Brigitta U.; Montejo, Angel L; Quail, Deborah; Dantchev, Nicolas; Demyttenaere, Koen; Garcia-Cebrian, Ana; Grassi, Luigi; Perahia, David G. S.; Reed, Catherine; Tylee, Andre

    2008-01-01

    Antidepressant prescribing patterns and factors influencing the choice of antidepressant for the treatment of depression were examined in the Factors Influencing Depression Endpoints Research (FINDER) study, a prospective, observational study in 12 European countries of 3468 adults about to start antidepressant medication for their first episode of depression or a new episode of recurrent depression. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly prescribed antidepress...

  8. [Do antidepressants really increase suicide rates in childhood and adolescence?].

    Science.gov (United States)

    Silva, Hernán; Martínez, Juan Carlos

    2007-09-01

    The use of antidepressant in depressive illness results in a reduction of suicidal attempts and deaths due to suicide, conditions that are generally present in this disorder. Recently, the Federal Drug Administration (FDA) prohibited the use of antidepressants during childhood and adolescence. This decision was based on a supposed increase in suicidal thinking in these age groups. However, the evidence came from flawed clinical studies, some of them not even published, in which no significant differences were observed when compared to placebo. It is not possible to ascribe a direct responsibility to antidepressants, because depression, by definition, has suicidal ideation. On the contrary, the reduction of suicidal rates supports the effectiveness of these medications. PMID:18064377

  9. A REVIEW ON HERBAL PLANTS SHOWING ANTIDEPRESSANT ACTIVITY

    Directory of Open Access Journals (Sweden)

    Talha Jawaid et al.

    2011-12-01

    Full Text Available Depression is a heterogenous mood disorder that has been classified and treated in variety of ways. Although a number of synthetic drugs are being used as standard treatment for clinically depressed patient, they have adverse effects that can compromise the therapeutic treatment .Thus, it is worthwhile to look for antidepressant from plants with proven advantage and favorable benefit to risk ratio. A number of medicinal plants and medicine derived from these plants have shown antidepressant properties by virtue of combined effect of their medicinal constituents. The causes of depression are decreased brain levels of monoamines like noradrenaline, dopamine and serotonin. Therefore, drugs restoring the reduced levels of these monoamines in the brain either by inhibiting monoamine oxidase or by inhibiting reuptake of these neurotransmitters might be fruitful in the treatment of depression. The present review is focused on the medicinal plants and plants based formulations having antidepressant activity in animal studies and in humans.

  10. Trimipramine: a challenge to current concepts on antidepressives.

    Science.gov (United States)

    Berger, M; Gastpar, M

    1996-01-01

    Although it is chemically a classical tricyclic antidepressant agent, trimipramine shows atypical pharmacological properties. Its well-documented antidepressant action cannot be explained by noradrenaline or serotonin reuptake inhibition or by a down-regulation of beta-adrenoceptors. Furthermore, its receptor affinity profile resembles more that of clozapine, a neuroleptic drug, than that of tricyclic antidepressants. Trimipramine does not reduce, but rather increases, rapid eye movement sleep. It stimulates nocturnal prolactin secretion and inhibits nocturnal cortisol secretion and may act at the level of the hypothalamus on corticotropin-releasing hormone secretion. Trimipramine is of particular value in depressed patients with insomnia, and it has been shown to be effective in the therapy of primary insomnia. As the pharmacological profile indicates, and an open clinical study has shown, trimipramine might also be active as an antipsychotic. The drug is both a tool for increasing our understanding of depression and a potential therapy for several psychiatric disorders. PMID:8863001

  11. [Critical evaluation of the use of antidepressives in childhood].

    Science.gov (United States)

    Conde López, V J; Ballesteros Alcalde, M C; Franco Martín, M A; Geijo Uribe, M S

    1997-01-01

    In the introduction the authors study some technical, methodological, ethical, administrative and marketing problems about the evaluation and investigation in child and adolescence psychopharmacology. They make a revision and critical evaluation about. As a whole the clinic use of antidepressive drugs in childhood psychiatry. Then, some open and controlled trial about tricyclic antidepressives are evaluated. After this, the authors present the most important advances about the open and controlled clinic trials with several antidepressives: tricyclic, tetracyclic, ISSR and MAO-Inhibitors and other drugs (placebo response, psychotherapy, imipramine, nortryptiline, amitriptyline, fluoxetine, MAO-Inhibitors, lithium, mianserin, maprotyline, etc.). Beside, placebo effect, response prediction factors, biologic markers, diagnostic criteria, evaluation methods and technics, drugs associations, clinic types of child depression, etc, are studied. In the last, the authors present some clinical conclusions about this subject. PMID:9245188

  12. 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.

  13. Increased use of antidepressants at the end of life

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... groups the use of antidepressants increases substantially with proximity to death in the last 3 years of life. In the last phase of life the use is independent of whether the patient dies at age 65 or 90 about 33% of females and 25% of males receive antidepressants in the last 6 months. CONCLUSIONS: The...

  14. Reconsidering GHB: orphan drug or new model antidepressant?

    Science.gov (United States)

    Bosch, Oliver G; Quednow, Boris B; Seifritz, Erich; Wetter, Thomas C

    2012-05-01

    For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders. PMID:21926421

  15. EMSAM (deprenyl patch): how a promising antidepressant was underutilized.

    Science.gov (United States)

    Asnis, Gregory M; Henderson, Margaret A

    2014-01-01

    The EMSAM patch is a unique monoamine oxidase inhibitor (MAOI) being the only antidepressant utilizing a transdermal delivery system. This was welcomed by clinicians who hoped that EMSAM would be better tolerated than oral MAOIs and non-MAOI antidepressants, as well as being effective for treatment in a wide spectrum of depressed patients including atypical depression, bipolar depression, and refractory depression. Unfortunately, the clinical use of EMSAM has been underutilized and its potential usefulness overlooked. This article suggests that fear of possible side effects, particularly the "cheese reaction" and serotonin syndrome, are some of the main contributors to underutilization by clinicians. These risks have been significantly exaggerated with the 6 mg/day dose not even requiring a special diet. Other contributing factors leading to underutilization are reviewed such as: the lack of studies addressing many important clinical questions; inadequate data analyses; not evaluating the effect of EMSAM on comorbid psychiatric conditions, particularly anxiety disorders; lack of antidepressant comparators versus EMSAM; no dose-response relationship examined; various depressive subtypes and conditions are unexplored, eg, bipolar depression and refractory depression; poor insurance coverage for an expensive medication; as well as minimal marketing efforts and postmarketing studies. On the other hand, many potential advantages of EMSAM are not highlighted enough in the literature and by pharmaceutical companies which might have increased clinical interest and utilization of the antidepressant. For example, the advantages of EMSAM include: avoidance of swallowing issues, as can be seen with oral antidepressants; minimal side effects, probably due to a favorable pharmacokinetic profile; minimal evidence of suicidal behavior, probably relating to the transdermal route of administration; low rates of inducing hypomanic/manic episodes; as well as significant efficacy in

  16. Psychiatric and Psychological Factors in Patient Decision Making Concerning Antidepressant Use

    Science.gov (United States)

    Dijkstra, Arie; Jaspers, Merlijne; van Zwieten, Marianne

    2008-01-01

    The observation that the use of antidepressants has strongly increased during the past decade implies that on a micro level doctors and patients more often decide that antidepressants are the appropriate treatment. Therefore, it is important to increase insight into patients' decision making regarding the use of antidepressants. The decision…

  17. Prognosis in heart failure and the value of {beta}-blockers are altered by the use of antidepressants and depend on the type of antidepressants used

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Gislason, Gunnar H; Poulsen, Henrik Enghusen;

    2009-01-01

    BACKGROUND: Depression worsens the prognosis in patients with cardiac disease, and treatment with antidepressants may improve survival. Guidelines recommend use of selective serotonin reuptake inhibitors (SSRIs), but knowledge of the prognostic effect of different classes of antidepressants...... death associated with antidepressants, HF medication, and coadministration of these 2 drug classes was estimated by Cox proportional hazard analyses. Propensity adjusted models were performed as sensitivity analysis. During the study period, there were 53 988 deaths, of which 83.0% were due...

  18. Patients’ treatment expectancies in clinical trials of antidepressants versus psychotherapy for depression: a study using hypothetical vignettes

    OpenAIRE

    Gaudiano, Brandon A.; Hughes, Jessica A.; Miller, Ivan W.

    2012-01-01

    Previous research on patients’ expectancies for improvement in clinical trials typically has been conducted after patients have already agreed to participate in a study. Depressed patients (n = 55) read 3 vignettes describing hypothetical clinical trials of antidepressant vs pill placebo, antidepressant vs antidepressant, and psychotherapy vs psychotherapy. Patients reported greater overall acceptability for psychotherapy over antidepressants. Patients had significantly greater expectancies f...

  19. Pharmacogenetic insights into depression and antidepressant response: does sex matter?

    Science.gov (United States)

    Pitychoutis, P M; Zisaki, A; Dalla, C; Papadopoulou-Daifoti, Z

    2010-01-01

    It is known that the frequency of men and women suffering from stress-related neuropsychiatric disorders is all but proportionally distributed. Notably, women are far more susceptible than men to the precipitation of depressive symptomatology. Some studies attribute this sex-specific vulnerability to the pronounced genetic predisposition that women may present towards the development of depressive disorders. Furthermore, clinical evidence support the notion that antidepressant response is also characterized by sex-specific manifestations; women may have a better outcome when treated with selective serotonin re-uptake inhibitors, in comparison to tricyclic antidepressants. Despite the fact that the contribution of the "genome" remains elusive when it comes to major depression, intriguing evidence has recently emerged pointing to sexually dimorphic influences of certain polymorphisms in genes related to the pathophysiology of major depression and antidepressant response, such as the serotonin transporter (5-HTT), serotonin 1A (5HT1A) receptor, monoamine oxidase A (MAO-A) and others. Given that the ultimate goal of pharmacogenetics is to provide "tailor-made" pharmacotherapies based on the genetic makeup of an individual, the factor of "sex" needs to be carefully addressed in disorders that are characterized by sex specific manifestations. The aim of the present article is to highlight the impact of sex in depression and in antidepressant pharmacoresponse by providing intriguing insights from the field of pharmacogenetics. PMID:20459391

  20. 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

    effect 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. (PsycINFO Database Record (c) 2012 APA, all...

  1. Antidepressant and anti-stress effects of curcumin inmice

    Institute of Scientific and Technical Information of China (English)

    YingXU; Bao-shanKU; Hai-yanYAO; Yong-heZHANG; Xue-junLI

    2004-01-01

    Curcumin (diferuloylmethane), a yellow colouring agent contained in the rhizome of Curcuma Longa (turmeric), has a wide array of pharmacological and biological activities, such as antioxidant, anti-inflammatory, immunomodulating and anticarcinogenic effects. In this study, curcumin was examined for the antidepressant and anti-stress effects in forced swimming,

  2. 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…

  3. Narrative Magic and the Construction of Selfhood in Antidepressant Advertising

    Science.gov (United States)

    Stepnisky, Jeffrey N.

    2007-01-01

    This article examines the way in which selfhood is constructed in direct-to-consumer advertisements for antidepressant medications. The sample consists of advertisements that appeared in nine popular magazines between 1997 and 2005, television commercials that ran between 2003 and 2005, and online promotional Web sites. The analysis is divided…

  4. The Association of Antidepressant Medication and Body Weight Gain.

    Directory of Open Access Journals (Sweden)

    Sara Ranjbar

    2013-04-01

    Full Text Available Objective: To review the literature and discover which antidepressants are responsible for weight gain and then to discuss the areas with lack of adequate knowledge. Method: An electronic search was conducted through Medline, Pubmed, Cochrane library, and ScienceDirect. Forty nine empirical researches were identified and reviewed. Results: Amitriptyline, clomipramine, and mirtazapine have been associated with more weight gain induction in clinical studies, but not in animal-based studies. All TCAs have been reported to cause weight gain except protriptyline. MAOIs have been associated with weight gain. In SSRI group, citalopram and ecitalopram induce weight, yet mixed results exist for paroxetine and fluoxetine. Researches unanimously reported weight loss effect for bupropion. Some studies suggest contributing factors in the relationship of antidepressants with body weight changes including age, gender, base-line weights and treatment duration. Various results of different treatment durations have been reported in some cases but there are not continuous time-dependent studies for the influences of antidepressants on body weight changes. Conclusion: More studies are required to discover underlying mechanisms and the time-dependent effects of antidepressants on body weight changes.

  5. Interaction of antidepressant drug fluoxetine with the metabolism of triiodothyronine

    Czech Academy of Sciences Publication Activity Database

    Pavelka, Stanislav

    Athens: University of Athens, 2009, s. 178-184. [International Symposium on Trace Elements in Human : New Perspectives /7./. Athens (GR), 13.10.2009-15.10.2009] R&D Projects: GA ČR(CZ) GA304/08/0256 Institutional research plan: CEZ:AV0Z50110509 Keywords : antidepressant drug * metabolism * thyroid hormone Subject RIV: ED - Physiology

  6. 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.

    2006-01-01

    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 cri

  7. Effects of Information on College Students' Perceptions of Antidepressant Medication

    Science.gov (United States)

    Frankenberger, Kristi A.; Frankenberger, William R.; Peden, Blaine F.; Hunt, Heather L.; Raschick, Christopher M.; Steller, Emily G.; Peterson, Jaclyn A.

    2004-01-01

    The authors examined the impact of pharmaceutical companies' advertisements on college students' perceptions of depression and concomitant treatment with antidepressants among 13 male and 31 female undergraduates from a midwestern university. The students were randomly assigned to groups that read either pharmaceutical company advertisements or…

  8. 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

  9. Antidepressants are selective serotonin neuronal reuptake inhibitors: 40-year history

    Directory of Open Access Journals (Sweden)

    D. S. Danilov

    2015-03-01

    Full Text Available The paper presents historical prerequisites for designing antidepressants from a group of selective serotonin neuronal reuptake inhibitors (SSRIs: to determine a lower serotonin concentration in the different tissues of depressed patients; to establish a higher serotonin concentration in the treatment of depressed patients with tricyclic antidepressants, and to formulate the serotonergic theory of depression. It also provides a consecutive account of the history of clinical introduction of individual SSRI representatives, such as fluoxetine, zimelidine, fluvoxamine, indalpine, citalopram, sertraline, paroxetine, and escitalopram. There are data from the history of studying the mechanism of SSRI action: from the theory of the importance of an increase in the concentration of serotonin in the synaptic cleft to the current understanding of complex successive intracellular rearrangements at the level of the postsynaptic neuron. The history of studying the efficacy of SSRIs in treating depression is considered in detail. Emphasis is laid on the reasons for a paradoxical difference in the evaluations of the efficiency of therapy with SSRIs versus other groups of antidepressants at different developmental stages of psychopharmacology. The role of marketing technologies in disseminating the data on the efficacy of this or that group of antidepressants is described. The practical significance of differences in individual SSRI representatives (the potency of serotonin uptake inhibition; the degree of selectivity and activity against the serotonergic system; the likelihood of an unfavorable pharmacokinetic interaction with other drugs; the half-life of elimination; the quickness of achieving a therapeutic dose is analyzed. Whether it is possible and reasonable to differentially choose different SSRI representatives in the treatment of depressions at the present stage is discussed. The authors state their belief that researches should be continued to

  10. Invivo antioxidant status: a putative target of antidepressant action.

    Science.gov (United States)

    Zafir, Ayesha; Ara, Anjum; Banu, Naheed

    2009-03-17

    Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Antidepressants are widely prescribed to treat these conditions; however, few animal studies have investigated the effect of these drugs on endogenous antioxidant status in the brain. The present study employed a 21-day chronic regimen of random exposure to restraint stress to induce oxidative stress in brain, and behavioural aberrations, in rodents. The forced swimming (FST) and sucrose preference tests were used to identify depression-like phenotypes, and reversal in these indices indicated the effectiveness of treatment with fluoxetine (FLU; 20 mg/kg/day, p.o.; selective serotonin reuptake inhibitor), imipramine (IMI; 10 mg/kg/day, p.o.; tricyclic antidepressant) and venlafaxine (VEN; 10 mg/kg/day, p.o.; dual serotonin/norepinephrine reuptake inhibitor) following restraint stress. The antioxidant status was investigated in the brain of these animals. The results evidenced a significant recovery in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione (GSH) levels by antidepressant treatments following a restraint stress-induced decline of these parameters. The severely accumulated lipid peroxidation product malondialdehyde (MDA) and protein carbonyl contents in stressed animals were significantly normalized by antidepressant treatments. The altered oxidative status is implicated in various aspects of cellular function affecting the brain. Thus, it is possible that augmentation of in vivo antioxidant defenses could serve as a convergence point for multiple classes of antidepressants as an important mechanism underlying the neuroprotective pharmacological effects of these drugs observed clinically in the treatment of various stress disorders. Consequently, pharmacological modulation of stress-induced oxidative damage as a possible stress-management approach should

  11. EMSAM (deprenyl patch: how a promising antidepressant was underutilized

    Directory of Open Access Journals (Sweden)

    Asnis GM

    2014-10-01

    Full Text Available Gregory M Asnis,1,2 Margaret A Henderson2 1Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY, USA; 2Anxiety and Depression Clinic, Montefiore Medical Center, New York, NY, USA Abstract: The EMSAM patch is a unique monoamine oxidase inhibitor (MAOI being the only antidepressant utilizing a transdermal delivery system. This was welcomed by clinicians who hoped that EMSAM would be better tolerated than oral MAOIs and non-MAOI antidepressants, as well as being effective for treatment in a wide spectrum of depressed patients including atypical depression, bipolar depression, and refractory depression. Unfortunately, the clinical use of EMSAM has been underutilized and its potential usefulness overlooked. This article suggests that fear of possible side effects, particularly the “cheese reaction” and serotonin syndrome, are some of the main contributors to underutilization by clinicians. These risks have been significantly exaggerated with the 6 mg/day dose not even requiring a special diet. Other contributing factors leading to underutilization are reviewed such as: the lack of studies addressing many important clinical questions; inadequate data analyses; not evaluating the effect of EMSAM on comorbid psychiatric conditions, particularly anxiety disorders; lack of antidepressant comparators versus EMSAM; no dose–response relationship examined; various depressive subtypes and conditions are unexplored, eg, bipolar depression and refractory depression; poor insurance coverage for an expensive medication; as well as minimal marketing efforts and postmarketing studies. On the other hand, many potential advantages of EMSAM are not highlighted enough in the literature and by pharmaceutical companies which might have increased clinical interest and utilization of the antidepressant. For example, the advantages of EMSAM include: avoidance of swallowing issues, as can be seen with oral antidepressants

  12. 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.

  13. 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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    -depth, qualitative interviews of 16 depressed patients one, four, eight and twelve months after hospital discharge supplemented by diagnostic interviews and self-report measures. Kleinman's notion of "explanatory model" was used as the theoretical perspective on the patients' illness narratives. Interview...... transcripts were analysed thematically with "explanatory models" as the starting point. RESULTS: Patients had ambiguous experiences of depression and antidepressants. Patients explained their illness and the medical treatment in experience-near terms. Explanations of the reasons for depression were...... 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....

  15. [Combined tricyclic antidepressants and ritalin in elderly depressives].

    Science.gov (United States)

    Naor, S; Talmon, Y; Guy, N

    1992-10-01

    Psychostimulants, including ritalin (methylphenidate), were used as antidepressives in the '50s but were then replaced by tricyclics and MAO inhibitors. Treatment of depression with psychostimulants is still controversial. Several anecdotal reports in the past decade approved the use of tricyclic antidepressants (TCA) together with methylphenidate in apathetic and withdrawal states in medically ill and in elderly patients. Ritalin elevates mood by releasing catecholamines and blocking their re-uptake, and also increases serum TCA levels. 5 men and 5 women between the ages of 65 and 79 were diagnosed as suffering from major depressive disorders, either single or recurrent, based on the Revised Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). They had been treated with TCA for up to several months with no response. Following addition of methylphenidate, 5-15 mg/d for 2 weeks, 4 men and 3 women improved rapidly, 2 of them within 24 hours. PMID:1459498

  16. [What is next in the development of antidepressives?].

    Science.gov (United States)

    Valchár, M

    1991-04-01

    After some findings concerning the mode of action of antidepressants, it was possible to hypothesize the molecular basis of depressive disorders (monoamine hypothesis, receptor hypothesis). These informations made the preparation of drugs acting by a completely new mechanism. Possible an antidepressant effect was observed after the administration of GABA-ergic agonists, or agents influencing dopaminergic transmission, S-adenosylmethionine, and drugs influencing second messenger systems. As a consequence of these findings, the GABA-ergic hypothesis, hypothesis of endogenous ligand (barinine hypothesis is discussed in more detail), and second messenger hypothesis of affective disorders were formulated. Agents influencing second messenger systems and S-adenosylmethionine seem to be a promising field of future investigation. PMID:1913947

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

    International Nuclear Information System (INIS)

    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

  18. The Antidepressant WebMarketing depression and making medicines work.

    Science.gov (United States)

    Medawar, C

    1997-01-01

    This paper was conceived as chapters two and three of the still unwritten book, and as a basis for discussion on an Internet website and elsewhere. These chapters examine hard evidence relating to a wholly rhetorical and hypothetical question, "Do antidepressants work?" The question provides the broadest possible framework for looking at the meaning and values of medicine. Implicitly, the question also asks: what is better than nothing, and how much better are antidepressant drugs than the placebos they are compared with in clinical trials? Between the lines of the paper lie basic questions about the ethics, activities, performance and impact of the three main centres of power in medicine - government, professionals and the pharmaceutical industry. The underlying issue is whether people who are miserably unfulfilled, sad, anguished or depressed are in hands as safe as they might imagine or need. PMID:23511318

  19. 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.

  20. The wisdom of crowds (vox populi) and antidepressant use.

    Science.gov (United States)

    Patten, Scott B

    2015-01-01

    Under certain conditions, groups of people may (collectively) make better judgments than experts. Galton connected this phenomenon to the phrase vox populi in a 1907 paper. Arguably, an example of the phenomenon may be found in recent stabilization of the frequency of antidepressant use, following decades of increases. There is no evidence that a change in physi-cian behaviour has caused this stabilization. The stable frequency more likely reflects decisions made by thousands of individual people based on their personal experiences. This may provide a statement from the vox populi on an optimal frequency of antidepressant use in contemporary populations under current conditions, a topic that has eluded the consensus of experts. PMID:25674154

  1. The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

    OpenAIRE

    Aton, Sara J.; Seibt, Julie; Dumoulin, Michelle C.; Coleman, Tammi; Shiraishi, Mia; Frank, Marcos G.

    2009-01-01

    Background Recent findings indicate that certain classes of hypnotics that target GABAA receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABAA receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, ...

  2. Perinatal Antidepressant Use: Understanding Women’s Preferences and Concerns

    OpenAIRE

    Battle, Cynthia L.; Salisbury, Amy L.; SCHOFIELD, CASEY A.; ORTIZ-HERNANDEZ, SAMIA

    2013-01-01

    Perinatal depression is prevalent and linked with a host of adverse consequences for women and newborns. Rates of engagement in depression treatment are, however, strikingly low among pregnant and postpartum women, with the majority of affected women receiving no mental health treatment. Research indicates that perinatal women are extremely reluctant to take antidepressant medications, yet the nature of women’s concerns and treatment decisionmaking patterns have not been well documented. Deve...

  3. Tricyclic antidepressant overdose: an unusual method of administration

    OpenAIRE

    Barton, Marc; Harris, Dan

    2010-01-01

    Drug poisoning as a result of tricyclic antidepressant overdose is frequently encountered in emergency departments and is a significant cause of mortality and morbidity. The usual route of administration is oral. Here we report the case of a 42-year-old man with a history of depression who had taken a large overdose of amitriptyline by the rectal route. This case highlights the management difficulties that arose as a result of rectal administration of the drug and possible ways in which treat...

  4. Translocator protein mediates the anxiolytic and antidepressant effects of midazolam.

    Science.gov (United States)

    Qiu, Zhi-Kun; Li, Ming-Sheng; He, Jia-Li; Liu, Xu; Zhang, Guan-Hua; Lai, Sha; Ma, Jian-Chun; Zeng, Jia; Li, Yan; Wu, Hong-Wei; Chen, Yong; Shen, Yong-Gang; Chen, Ji-Sheng

    2015-12-01

    The translocator protein (18 kDa) (TSPO) plays an important role in stress-related disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD), caused by neurosteroids (e.g. allopregnanolone). The present study sought to evaluate the significance of TSPO in anxiolytic and antidepressant effects induced by midazolam. The animals were administrated midazolam (0.25, 0.5 and 1 mg/kg, i.p.) and subjected to behavioral tests, including Vogel-type conflict test, elevated plus-maze test, forced swimming test. Midazolam produced anxiolytic- and antidepressant-like effects Vogel-type conflict test (1 mg/kg, i.p.), elevated plus-maze test (0.5 and 1 mg/kg, i.p.), and forced swimming test (0.5 and 1 mg/kg, i.p.). These effects of Midazolam were totally blocked by the TSPO antagonist PK11195 (3 mg/kg, i.p.). To evaluate the role of allopregnanolone in the anxiolytic- and antidepressant-like effects of midazolam, the animals were decapitated at the end of the behavioral tests. The allopregnanolone levels of the prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The allopregnanolone level of the prefrontal cortex and hippocampus was increased by midazolam (0.5, 1 mg/kg, i.p.) and the increase was reversed by PK11195 (3 mg/kg, i.p.). Overall, the results indicated that the anxiolytic- and antidepressant-like effects of midazolam were mediated by TSPO, via stimulation of allopregnanolone biosynthesis. PMID:26455280

  5. Drug Interaction in Psycho-Oncology: Antidepressants and Antineoplastics

    OpenAIRE

    de Miguel, C; E. Albuquerque

    2011-01-01

    Background and Objectives: Although there is a growing impact of psychiatric and depressive disorders in cancer patients, literature on the idiosyncrasies of antidepressants (ADs) used in those conditions and their interactions with antineoplastic agents (ANs) is scarce. Sharing the same biotransformation pathways enhances the risk of drug interaction between ADs and ANs, specifically when compounds are inducers, inhibitors or substrates of cytochrome P450 (CYP 450). In cancer patients, such ...

  6. Mechanisms underlying the antidepressant response and treatment resistance

    OpenAIRE

    Levinstein, Marjorie R.; Samuels, Benjamin A.

    2014-01-01

    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 ...

  7. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    OpenAIRE

    Marjorie Rose Levinstein; Benjamin Adam Samuels

    2014-01-01

    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 ...

  8. Tricyclic antidepressant overdose treated with adjunctive lipid rescue and plasmapheresis

    OpenAIRE

    Odigwe, Chibuzo Clement; Tariq, Madiha; Kotecha, Tulsi; Mustafa, Usman; Senussi, Nizar; Ikwu, Isaac; Bhattarcharya, Anirban; Ngene, John Ifeanyi; Ojiako, Kizito; Iroegbu, Nkemakolam

    2016-01-01

    Tricyclic antidepressant poisoning remains a major cause of morbidity and mortality, particularly in the setting of suicidal attempts. The current standard of care for treatment is the administration of sodium bicarbonate infusion. Adjunctive lipid emulsion therapy and plasmapheresis have received attention recently. We report an 18-year-old patient who was successfully managed with lipid emulsion and plasmapheresis as adjuncts to sodium bicarbonate treatment and review some of the recent lit...

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

    OpenAIRE

    Reshmi L. Singh, Ph.D; College of Pharmacy, University of Minnesota; Marcia M. Worley, Ph.D.; Cynthia Peden-McAlpine, Ph.D.

    2012-01-01

    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, phenomen...

  10. [Antidepressant active constituents in the roots of Morinda officinalis How].

    Science.gov (United States)

    Cui, C; Yang, M; Yao, Z; Cao, B; Luo, Z; Xu, Y; Chen, Y

    1995-01-01

    Five compounds having antidepressant activities have been isolated from the roots of Morinda officinalis, a Chinese traditional Yang-tonic drug. These compounds were identified as succinic acid (1), nystose (2), 1F-fructofuranosylnystose (3), inulin-type hexasaccharide (4) and heptasaccharide (5) by chemical and spectroscopic methods. All of the compounds are isolated from the species of genus Morinda for the first time. PMID:7626209

  11. Synthesis of antidepressant duloxetine via asymmetric transfer hydrogenation

    Institute of Scientific and Technical Information of China (English)

    Shan Zhen He; Xue Ming Li; Jia Dai; Ming Yan

    2008-01-01

    Antidepressant duloxetine (1) was prepared via asymmetric transfer hydrogenation of 3-(dimethylamino)-1-(thiophen-2-yl)propan-1-one (3). The Ru(Ⅱ), Rh(Ⅲ) and Ir(Ⅲ) complexes of several chiral ligands were examined as the catalyst and(S,S)-N-tosyl-1,2-diphenyl ethylenediamine (TsDPEN)-Ru(Ⅱ) complex was found to provide good yield and excellent enantios-electivity.

  12. 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.

  13. Antidepressants versus placebo in major depression: an overview

    OpenAIRE

    KHAN, Arif; Walter A Brown

    2015-01-01

    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 d...

  14. Tricyclic antidepressant overdose treated with adjunctive lipid rescue and plasmapheresis.

    Science.gov (United States)

    Odigwe, Chibuzo Clement; Tariq, Madiha; Kotecha, Tulsi; Mustafa, Usman; Senussi, Nizar; Ikwu, Isaac; Bhattarcharya, Anirban; Ngene, John Ifeanyi; Ojiako, Kizito; Iroegbu, Nkemakolam

    2016-07-01

    Tricyclic antidepressant poisoning remains a major cause of morbidity and mortality, particularly in the setting of suicidal attempts. The current standard of care for treatment is the administration of sodium bicarbonate infusion. Adjunctive lipid emulsion therapy and plasmapheresis have received attention recently. We report an 18-year-old patient who was successfully managed with lipid emulsion and plasmapheresis as adjuncts to sodium bicarbonate treatment and review some of the recent literature. PMID:27365872

  15. Antidepressant effect of Melissa officinalis in the forced swimming test

    Directory of Open Access Journals (Sweden)

    M Emamghoreishi

    2009-03-01

    Full Text Available ABSTRACT Background: In Iranian and other traditional medicines, an antidepressant effect has been indicated for Melissa officinalis (Lamiaceae. However, studies showing its antidepressant effect is lacking. Therefore, the present study was undertaken to examine whether the aqueous extract and essential oil from leaves of Melissa officinalis have an antidepressant-like activity in mice.  Materials and Methods: The effect of subchronic administration of different doses of the aqueous extract (25, 75, 150, 300 mg/kg or water; n=9-10 and the essential oil (10, 25, 75, 150, 300 mg/kg or almond oil; n=9-10 on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test. Fluoxetine (20mg/kg and imipramine (15 mg/kg were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. Results: All doses of the aqueous extract, used in this study, produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. Essential oil caused a dose-dependent reduction in immobility and an increase in climbing at all studied doses, compared to control group. Only the highest dose (300mg/kg of essential oil showed a significant increase in swimming behavior. The aqueous extract, but not the essential oil, decreased spontaneous activity in a dose dependent manner. Conclusion: The results of this study suggests that the Melissa officinalis possess an antidepressant-like activity similar to imipramine which may have a potential clinical value for treatment of depression.

  16. Antidepressant Treatment for Acute Bipolar Depression: An Update

    OpenAIRE

    Amit, Ben H.; Abraham Weizman

    2012-01-01

    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 subje...

  17. The Wisdom of Crowds (Vox Populi) and Antidepressant Use

    OpenAIRE

    Patten, Scott B

    2015-01-01

    Under certain conditions, groups of people may (collectively) make better judgments than experts. Galton connected this phenomenon to the phrase vox populi in a 1907 paper. Arguably, an example of the phenomenon may be found in recent stabilization of the frequency of antidepressant use, following decades of increases. There is no evidence that a change in physi-cian behaviour has caused this stabilization. The stable frequency more likely reflects decisions made by thousands of individual pe...

  18. Neuroplasticity and the next wave of antidepressant strategies.

    Science.gov (United States)

    Hayley, Shawn; Litteljohn, Darcy

    2013-01-01

    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 N-methyl-D-aspartate (NMDA) antagonist, ketamine, which already has well documented rapid antidepressant effects, and the trophic cytokine, erythropoietin (EPO), which we propose as a potential adjunctive antidepressant agent. PMID:24312008

  19. 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.

  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. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students

    Directory of Open Access Journals (Sweden)

    Vo K

    2015-01-01

    Full Text Available Kim Vo,1 Patricia J Neafsey,2 Carolyn A Lin3 1University of Connecticut Health Center, Farmington, 2School of Nursing and Center for Health Information and Prevention, University of Connecticut, Storrs, 3Department of Communication Sciences and Center for Health Information and Prevention, University of Connecticut, Storrs, CT, USA Abstract: Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Significant differences were found between students reporting (n=79; 4.0% and not reporting (n=1,897; 96% amphetamine-stimulant use in the past month – in terms of race/ethnicity, class standing, residence, health symptoms, self-health report – in addition to alcohol, tobacco, pain-reliever, and antidepressant use. Health symptoms reported more often by stimulant users included depression, diarrhea, difficulty sleeping, fatigue, dizziness, difficulty concentrating, and nicotine craving. Health care providers of college students should query these patients about symptoms that could be related to depression and amphetamine use. In particular, they should provide education at the point of care around the risks of amphetamine use in general and the specific risks in those students who have symptoms of depression and/or are taking antidepressant medication. Prevention programs should also target the risks of concurrent use of amphetamines, antidepressants, and other drugs among college students. Keywords: stimulant use, depression, college students, self-medication

  2. Effects of antidepressants on P2X7 receptors.

    Science.gov (United States)

    Wang, Wei; Xiang, Zheng-Hua; Jiang, Chun-Lei; Liu, Wei-Zhi; Shang, Zhi-Lei

    2016-08-30

    Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6-12 but not by acute application (10µM) or pre-incubation for 2-6h at a dose of 1µM, 3µM or 10µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects. PMID:27318632

  3. Second-tier natural antidepressants: review and critique.

    Science.gov (United States)

    Iovieno, Nadia; Dalton, Elizabeth D; Fava, Maurizio; Mischoulon, David

    2011-05-01

    The use of Complementary and Alternative Medicine (CAM) for physical and mental problems has increased significantly in the US over the past two decades, and depression is one of the leading indications for the use of CAM. This article reviews some of the lesser-known natural products with potential psychiatric applications that are starting to emerge with some scientific and clinical evidence and may constitute a next wave of natural antidepressants: Rhodiola rosea, chromium, 5-Hydroxytryptophan (5-HTP) and inositol. Background information, efficacy data, proposed mechanisms of action, recommended doses, side effects, and precautions are reviewed. We found some encouraging data for the use of these natural products in specific populations of depressed patients. R. rosea is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects. Chromium has a beneficial effect on eating-related atypical symptoms of depression, and may be a valuable agent in treating atypical depression and seasonal affective disorder. Inositol may be useful in the treatment of bipolar depression when combined with mood stabilizers. Evidence for the clinical efficacy of 5-HTP is also promising but still preliminary. Although more well-designed and larger controlled studies are needed before any substantive conclusions can be drawn, the available evidence is compelling and these natural products deserve further investigation as a possibly significant addition to the antidepressant armamentarium. PMID:20579741

  4. [Antidepressives of the 3rd, 4th and 5th generation].

    Science.gov (United States)

    Svestka, J

    1994-02-01

    Antidepressants are classified into five generations. Preparations of the first generation affect various neurotransmitter systems and are therefore associated with many undesirable effects (e.g. tricyclic antidepressants, maprotiline). The second generation of antidepressants is already devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker (e.g. mianserine, mirtazapine, trazodone). The antidepressant action of preparations of the third generation is mediated only by one of the three main neurotransmitter systems for depression (5-HT, noradrenaline, dopamine) and does not affect muscarine, histamine and adrenergic cerebral systems (e.g. SSRI, ipsapirone, viloxazine, reboxetine, bupropione). Recently antidepressants of the fourth generation were synthetized which influence only the serotonin, and noradrenaline or dopamine system (e.g. milnacipran, befloxatone). The fifth generation of antidepressants foresees the exclusive action on 5-HT, noradrenaline and dopamine systems of the CNS in varying ratios (e.g. venlafaxine, cericlamine). PMID:8174184

  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

    Treatment with some types of antidepressants has been associated with sudden cardiac death. It is unknown whether the increased risk is due to a class effect or related to specific antidepressants within drug classes. All patients in Denmark with an out-of-hospital cardiac arrest (OHCA) were...... identified (2001-2007). Association between treatment with specific antidepressants and OHCA was examined by conditional logistic regression in case-time-control models. We identified 19,110 patients with an OHCA; 2,913 (15.2%) were receiving antidepressant treatment at the time of OHCA, with citalopram...... 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...

  6. Evaluation of antidepressant and analgesic activity of tapentadol with mirtazapine: an experimental study

    OpenAIRE

    Pankaj K. Chaudhary; Atul Jain; Asha Pathak; Neha Sharma; Atul K. Mishra; Arvind K. Maurya; Vikas Gaur

    2015-01-01

    Background: Data comparing tapentadol with an antidepressant is limited. A comparison of tapentadol with mirtazapine at different dose has not been performed, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that tapentadol should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a study evaluate antidepressant and analgesic activi...

  7. The effect of knowledge and expectations on adherence to and persistence with antidepressants

    OpenAIRE

    Woodward SC; Bereznicki BJ; Westbury JL; Bereznicki LR

    2016-01-01

    Sophie Claire Woodward, Bonnie Jayne Bereznicki, Juanita Louise Westbury, Luke Ryan Elliot Bereznicki Pharmacy, School of Medicine, University of Tasmania, Hobart, TAS, Australia Purpose: Adherence to and persistence with antidepressants are often suboptimal. However, little is known about how patient knowledge and outcome expectations may influence antidepressant adherence and persistence.Method: Individuals who had been prescribed their first antidepressant to treat depression in the preced...

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

    Directory of Open Access Journals (Sweden)

    Harada T

    2014-11-01

    Full Text Available Tsuyoto Harada, Ken Inada, Kazuo Yamada, Kaoru Sakamoto, Jun Ishigooka Department of Psychiatry, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan Objective: Patients often develop neuropsychiatric symptoms such as anxiety and agitation after they have started taking an antidepressant, and this is thought to be associated with a potentially increased risk of suicide. However, the incidence of antidepressant-induced jitteriness/anxiety syndrome has not been fully investigated, and little has been reported on its predictors. The aim of this study was to survey the incidence of antidepressant-induced jitteriness/anxiety syndrome and clarify its predictors in a natural clinical setting.Materials and methods: Between January 2009 and July 2012, we prospectively surveyed 301 patients who had not taken any antidepressants for 1 month before presentation, and who were prescribed antidepressants for 1 month after their initial visit. Patients were classified as developing antidepressant-induced jitteriness/anxiety syndrome if they experienced any symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania during the first month.Results: Among the 301 patients, 21 (7.0% developed antidepressant-induced jitteriness/anxiety syndrome. Major depressive disorder and a diagnosis of mood disorder in first-degree relatives of patients were significantly associated with induction of antidepressant-induced jitteriness/anxiety syndrome (odds ratio 10.2, P=0.001; odds ratio 4.65, P=0.02; respectively. However, there was no such relationship for sex, age, class of antidepressant, combined use of benzodiazepines, or diagnosis of anxiety disorder.Conclusion: The findings of this study suggest that major depressive disorder and a diagnosis of mood disorder in first-degree relatives may be clinical predictors of antidepressant-induced jitteriness/anxiety syndrome

  9. 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 p...... intake consecutive to a chronic mild stress. These findings point out 5-HT(4) receptor agonists as a putative class of antidepressants with a rapid onset of action. Udgivelsesdato: 2007-Sep-6...

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

    OpenAIRE

    Gomez, R.; Huber, J.; G. Tombini; H.M.T. Barros

    2001-01-01

    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...

  11. Enhanced Antidepressant-Like Effects of Electroacupuncture Combined with Citalopram in a Rat Model of Depression

    OpenAIRE

    Yang, Jian; Pei, Yu; Pan, Yan-Li; Jia, Jun; Shi, Chen; Yu, Yan; Deng, Jia-Hui; Li, Bo; Gong, Xiao-Li; Wang,Xuan; Xiao-min WANG; Ma, Xin

    2013-01-01

    Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we ...

  12. Effects of calcium channel blocker, nifedipine, on antidepressant activity of fluvoxamine, venlafaxine and tianeptine in mice

    OpenAIRE

    SHARMA, Ashok K.; Anjan Khadka; Navdeep Dahiya

    2015-01-01

    Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fluvoxamine, venlafaxine and tianeptine is limited. Hence, the present study wa...

  13. `I'd rather not take Prozac': stigma and commodification in antidepressant consumer narratives

    OpenAIRE

    Smardon, Regina

    2008-01-01

    Abstract This article explores the idea that narrative is the primary vehicle through which antidepressant consumers negotiate their sense of identity and reality. Antidepressant consumers represent a unique consumer culture because of the stigma that society attaches to mental illness. Recent media attention, including direct to consumer (DTC) advertising, appears to decrease the stigma surrounding antidepressant use while at the same time commodifying and branding them for mass c...

  14. Late-life depression and mortality: influence of gender and antidepressant use.

    OpenAIRE

    Ryan, Joanne; Carriere, Isabelle; Ritchie, Karen; Stewart, Robert; Toulemonde, Gwladys; Dartigues, Jean-François; Tzourio, Christophe; Ancelin, Marie-Laure

    2008-01-01

    Background Depression may increase the risk of mortality among certain subgroups of older people, but the part played by antidepressants in this association has not been thoroughly explored. Aims To identify the characteristics of older populations who are most at risk of dying, as a function of depressive symptoms, gender and antidepressant use. Method Adjusted Cox proportional hazards models were used to determine the association between depression and/or antidepressant use and 4-year survi...

  15. Long-term antidepressant use: patient perspectives of benefits and adverse effects

    Science.gov (United States)

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

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

    International Nuclear Information System (INIS)

    The histamine-H1 receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a 3H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H1 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-H1 receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs

  17. Antidepressants for bipolar disorder A meta-analysis of randomized, double-blind, controlled trials

    Institute of Scientific and Technical Information of China (English)

    Yingli Zhang; Huan Yang; Shichang Yang; Wei Liang; Ping Dai; Changhong Wang; Yalin Zhang

    2013-01-01

    OBJECTIVE: To examine the efficacy and safety of short-term and long-term use of antidepres-sants in the treatment of bipolar disorder. DATA SOURCES:A literature search of randomized, double-blind, control ed trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Control ed Trials databases. The keywords“bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed mania and depression, rapid cycling and bipolar disorder”, AND “antidepressant agent, antidepressive agents second-generation, antidepressive agents tricyclic, monoamine oxidase inhibitor, noradrenaline uptake in-hibitor, serotonin uptake inhibitor, and tricyclic antidepressant agent” were used. The studies that were listed in the reference list of the published papers but were not retrieved in the above-mentioned databases were supplemented. STUDY SELECTION: Studies selected were double-blind randomized control ed trials assessing the efficacy and safety of antidepressants in patients with bipolar disorder. Al participants were aged 18 years or older, and were diagnosed as having primary bipolar disorder. Antidepressants or antidepressants combined with mood stabilizers were used in experimental interventions. Placebos, mood stabilizers, antipsychotics and other antide pressants were used in the control interventions. Studies that were quasi-randomized studies, or used antidepressants in combination with antipsy-chotics in the experimental group were excluded. Al analyses were conducted using Review Man-ager 5.1 provided by the Cochrane Col aboration. MAIN OUTCOME MEASURES:The primary outcome was the response and switching to mania. The secondary outcomes included remission, discontinuation rate, and suicidality. RESULTS: Among 5 001 treatment studies published, 14 double-blind randomized control ed trials involving 1 244 patients were included in the meta

  18. 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.

  19. Treatment of Generalized Anxiety Disorder: A Comprehensive Review of the Literature for Psychopharmacologic Alternatives to Newer Antidepressants and Benzodiazepines

    OpenAIRE

    Huh, John; Goebert, Deborah; Takeshita, Junji; Lu, Brett Y.; Kang, Mark

    2011-01-01

    Objective: Generalized anxiety disorder (GAD) is common, chronic, and debilitating. Treatment with benzodiazepines and newer antidepressants is often inadequate. This article reviews the effectiveness of alternative and augmenting medications, such as older antidepressants, antipsychotics, anticonvulsants, and β-blockers.

  20. Antidepressant Effects of Resveratrol in an Animal Model of Depression

    Science.gov (United States)

    Akinfiresoye, Laura L. Hurley, Luli; Kalejaiye, Olubukola; Tizabi, Yousef

    2014-01-01

    Resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a natural non-flavonoid polyphenol antioxidant extracted from red grapes in the processing of wine. Initially it was studied for its potential as anticancer drug, and later was found to reduce cardiovascular disease. More recently resveratrol was shown to alleviate depressive-like symptoms induced by stress or other means in mice and rats. The major purpose of this study was to investigate whether resveratrol would manifest an antidepressant effect in Wistar-Kyoto (WKY) rats, a putative and non-induced animal model of depression, and whether this effect might be associated with an increase in hippocampal and frontal cortical brain-derived neurotrophic factor (BDNF), a protein implicated in chronic effects of many antidepressants. Adult male WKY rats were injected with two doses of resveratrol (10 and 40 mg/kg, i.p.) and their behavior in the open field locomotor activity (LMA), forced swim test (FST: a measure of helplessness), and sucrose preference test (SPT: a measure of anhedonia) was evaluated after a single acute injection or following 7 days of daily treatment. Both acute and chronic administration of resveratrol resulted in a dose-dependent decrease in FST. However, only chronic resveratrol resulted in dose-dependent increase in sucrose consumption. LMA was not affected by any treatment. Parallel to the observed behavioral effects the level of hippocampal, but not frontal cortical, BDNF was also dose-dependently elevated after chronic resveratrol administration. These findings indicate an antidepressant-like effect of resveratrol in an animal model of depression possibly via activation of hippocampal BDNF, and suggest therapeutic potential of resveratrol in at least a subpopulation of depressed patients. PMID:24717328

  1. Evaluation of antidepressant activity of vanillin in mice

    OpenAIRE

    Ahsan Shoeb; Mukta Chowta; Gokul Pallempati; Amritha Rai; Ashish Singh

    2013-01-01

    Objective: The main objective of this study was to evaluate antidepressant activity of vanillin in mice models of depression. Materials and Methods: 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 (10mg/kg and 100mg/kg). All the drugs were administered orally one hour before the test procedure for acute s...

  2. 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....

  3. Antidepressant-induced Remission of Gardner Diamond Syndrome

    Directory of Open Access Journals (Sweden)

    Neena Sanjiv Sawant

    2012-01-01

    Full Text Available We describe the clinical presentation of a 25-year-old female patient who presented in dermatology with recurrent episodes of painful ecchymotic bruising over the anterior aspect of both arms and face. On enquiry, these episodes were precipitated by emotional stress and were preceded with a history of fall from the stairs. The patient also had multiple stressors in her day-to-day life and symptoms of depression. A diagnosis of mild depressive disorder without somatic complaints and Gardner Diamond syndrome was made. The patient was started on antidepressants, which not only improved her mood symptoms but also caused a remission of her painful bruises.

  4. [Between depression and fibroniyalgia: the fate of the antidepressant].

    Science.gov (United States)

    Drobizhev, M Yu; Fedotova, A V; Kikta, S V; Antokhin, E Yu

    2016-01-01

    The authors present the information about one of the least studied antidepressants- milnacipran. Recommendations of its clinical use have been long based on incorrect conceptions of its pharmacological properties. Currently, milnacipran is considered as ancirepinephrine and serotonin (to a lesser degree) reuptake inhibitor and NMDA receptor blocker. Milnacipran can be successfully used in apatic, asthenic, adynamic and anhedonic depressions as well as in fibromyalgia in patients with marked fatigability and pain. However the recommendations for the latter are not registered in Russia (maybe due to the differences in the diagnosis of fibromyalgia which is traditionally more often diagnosed as neurasthenia). PMID:27386594

  5. Ketamine enantiomers in the rapid and sustained antidepressant effects.

    Science.gov (United States)

    Muller, John; Pentyala, Sahana; Dilger, James; Pentyala, Srinivas

    2016-06-01

    Recent evidence has suggested that the N-methyl-D-aspartate receptor antagonist ketamine shows significant therapeutic effects in major depression and bipolar disorder. This effect is especially important in treatment-resistant depression and depression with suicidal ideation. In this review we explain the mechanism of action, drug efficacy, and the side effects of ketamine; the antidepressive effects of ketamine; the individual effects of ketamine isomers, R(-) ketamine and S(+) ketamine; the effects of the combination of ketamine with electroconvulsive therapy; and the possible use of ketamine in treating depression. PMID:27354907

  6. 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. Popula

  7. Hippocampal volume correlates with attenuated negative psychotic symptoms irrespective of antidepressant medication

    Directory of Open Access Journals (Sweden)

    Raffaele Bernasconi

    2015-01-01

    Conclusion: Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.

  8. Antidepressants self-poisoning and ICU admissions in a University Hospital in the Netherlands

    NARCIS (Netherlands)

    Bosch, Tessa M.; van der Werf, Tjip S.; Uges, Donald R.A.; Ligtenberg, Jack .M.J; Fijen, Jan-Willem; Tulleken, Jaap E.; Zijlstra, Jan G.

    2000-01-01

    Objectives: Many overdosed patients are admitted to an ICU. Antidepressants are frequently used. We examined clinical end-points of toxicity recorded during admission to our ICU of all antidepressants used in overdose. Design: Single centre; retrospective analysis, 5 consecutive years (1994 - 1998).

  9. 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…

  10. Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels.

    Science.gov (United States)

    Tsai, Shih-Jen

    2006-01-01

    Major depressive disorder (MDD) is a common mental disease, but with an unknown etiology. Antidepressants are the main biological treatment for MDD. However, current antidepressive agents have a slow onset of effect and a substantial proportion of MDD patients do not clinically improve, despite maximal medication. Thus, the exploration for new antidepressants with novel strategies may help to develop faster and more effective antidepressant agents. Studies in the recent decades have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may play an important role in their therapeutic mechanism. Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule. Recent work has found that cysteamine and a related agent, cystamine, have neuroprotective effects in Huntington's disease (HD) mice, through enhancing central BDNF levels. Furthermore, cystamine or cysteamine injection could increase serum BDNF levels in wild-type mice as well as HD mice. Since activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, cystamine or its derivatives could have potential antidepressant therapeutic effects. Among these agents, pantethine may be one of the most promising agents. It is a naturally occurring compound which can be administered orally with negligible side effects, and is metabolized to cysteamine. Further evaluation of the therapeutic and toxic effects of these cysteamine-related antidepressant agents in MDD animal models is needed before any clinical application. PMID:16797865

  11. Antidepressant Use and Body Mass Index Change in Overweight Adolescents: A Historical Cohort Study

    OpenAIRE

    Cockerill, Richard G.; Biggs, Bridget K.; Oesterle, Tyler S.; Croarkin, Paul E.

    2014-01-01

    Objective: Given the limited empirical data on antidepressant use and weight change in children, we performed a historical cohort study to assess change in age- and sex-standardized body mass index associated with antidepressant use among overweight adolescents diagnosed with a depressive disorder.

  12. 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 p

  13. Psychiatric and psychological factors in patient decision making concerning antidepressant use

    NARCIS (Netherlands)

    Dijkstra, Arie; Jaspers, Merlijne; van Zwieten, Marianne

    2008-01-01

    The observation that the use of antidepressants has strongly increased during the past decade implies that on a micro level doctors and patients more often decide that antidepressants are the appropriate treatment. Therefore, it is important to increase insight into patients' decision making regardi

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

    DEFF Research Database (Denmark)

    Jensen, Hans Mørch; Grøn, Randi; Lidegaard, Øjvind; Pedersen, Lars Henning; Andersen, Per Kragh; Kessing, Lars Vedel

    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....

  15. 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.

  16. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    Science.gov (United States)

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  17. 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.

  18. Antidepressants in the treatment of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Popper, C W

    1997-01-01

    Antidepressants differ in their effectiveness for treating attention-deficit/hyperactivity disorder (ADHD) in adults and children. None are as effective as psychostimulants for treating the attentional and cognitive symptoms, but they can help reduce impulsive and hyperactive behavior. Tricyclic antidepressants have well-demonstrated efficacy in treating behavioral symptoms, but desipramine should be avoided, at least in youths and adolescents (and perhaps adults), because safer tricyclics are available. Bupropion was effective in its few controlled trials, but tics and (especially in youth) skin rash limit its value. Venlafaxine appears effective, but controlled studies are needed. Serotonin selective reuptake inhibitors have not been tested in controlled trials, but they cause inconsistent changes, often aggravate ADHD symptoms, and can cause frontal apathy and disinhibition. Clonidine has not been adequately examined but seems to have small or uncertain effects. Psychostimulants remain the treatment of choice because of their unique effect on attention. Multimodal treatments (medications plus psychosocial) might not be more effective than medications alone. PMID:9418743

  19. Secondary Metabolites from Three Florida Sponges with Antidepressant Activity

    Science.gov (United States)

    Kochanowska, Anna J.; Rao, Karumanchi V.; Childress, Suzanne; El-Alfy, Abir; Matsumoto, Rae R.; Kelly, Michelle; Stewart, Gina S.; Sufka, Kenneth J.; Hamann, Mark T.

    2016-01-01

    Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety–depression continuum model. Among the isolated compounds, 5,6-dibromo-N,N-dimethyltryptamine (1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo-N,N-dimethyltryptamine (2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs. PMID:18217716

  20. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    Science.gov (United States)

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. PMID:27089522

  1. Antidepressant and Anxiolytic Effects of Cod Liver Oil in Rats

    Directory of Open Access Journals (Sweden)

    Tahira Perveen*, Faiza Razi, Saida Haider, Hina Qayyum and Darakhshaan J. Haleem

    2013-01-01

    Full Text Available Cod-liver oil is a rich source of omega 3 fatty acids and has been widely used as omega 3 fatty acids supplementation. Regarding omega-3 fatty acid beneficial effects in humans, this study was designed to investigate the effect of repeated administration of cod-liver oil on the locomotion and behaviors of rats, including depression, anxiety and the 5-Hydroxy tryptamine (5-HT metabolism. After four weeks oral administration of cod-liver oil, open field test was used to measure the locomotor and exploratory activity. Elevated plus maze test was used to measure anxiety. Cod-liver oil significantly increased locomotion and produced anxiolytic effects in rats. Antidepressant effect of cod-liver oil was monitored by forced swim test (FST in which struggling time of test animals was increased significantly. 5-HT turnover also increased significantly following the oral repeated administration of cod liver oil in test animals. The results suggest that cod-liver oil has antidepressant and anti-anxiety effects.

  2. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

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    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.

  3. Common mechanisms of pain and depression: Are antidepressants also analgesics?

    Directory of Open Access Journals (Sweden)

    Tereza Nekovarova

    2014-03-01

    Full Text Available Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system. The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.

  4. Antidepressant treatment of the depressed patient with insomnia.

    Science.gov (United States)

    Thase, M E

    1999-01-01

    Sleep disturbances are an integral part of depressive disorder. As such, they are a part of all contemporary sets of diagnostic criteria for major depression and of all major symptom-based rating scales for depression. Insomnia is a particularly frequent complaint, and it is reported by more than 90% of depressed patients. Although the "kindling" or "illness transduction" model of depression remains hypothetical, there is evidence that people with recurrent depression have more pronounced abnormalities of sleep neurophysiology than those experiencing a single or initial episode. Therefore, early relief of insomnia in a depressed patient, in addition to alleviating other symptoms, may increase adherence to treatment and increase daytime performance and overall functioning, while complete relief of insomnia may improve prognosis. Stimulation of serotonin-2 (5-HT2) receptors is thought to underlie insomnia and changes in sleep architecture seen with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This is the reason why hypnotics or low-dose trazodone are commonly coprescribed at the initiation of the treatment with either the SSRIs or SNRIs. On the other hand, antidepressant drugs with 5-HT2 blocking properties, such as mirtazapine or nefazodone, alleviate insomnia and improve sleep architecture. In depressed patients, mirtazapine produces a significant shortening of sleep-onset latency, increases a total sleep time, and leads to a marked improvement in sleep efficiency. Antidepressants with preferential 5-HT2 blocking properties are therefore a good treatment option for depressed patients with marked insomnia. PMID:10446739

  5. 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.

  6. 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. PMID:27150557

  7. 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.

  8. Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.

    Science.gov (United States)

    Lin, Jen-Cheng; Lee, Mei-Yi; Chan, Ming-Huan; Chen, Yi-Chyan; Chen, Hwei-Hsien

    2016-09-01

    Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia. PMID:27363702

  9. Increased use of antidepressants and decreasing suicide rates: a population-based study using Danish register data

    DEFF Research Database (Denmark)

    Erlangsen, Annette; Canudas-Romo, V.; Conwell, Yeates

    2008-01-01

    OBJECTIVE: The objective of the present study was to examine if the change in the suicide rate is associated with individuals' use of antidepressants as has been suggested by ecological studies. DESIGN: Decomposition of suicide rates by antidepressant treatment group. SETTING: Population-based re...... antidepressants seem to account for 10% of the decline in the suicide rate. Nevertheless, suicides might be prevented by more effective treatment......OBJECTIVE: The objective of the present study was to examine if the change in the suicide rate is associated with individuals' use of antidepressants as has been suggested by ecological studies. DESIGN: Decomposition of suicide rates by antidepressant treatment group. SETTING: Population......-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...

  10. Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.

    Science.gov (United States)

    Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

    2012-05-01

    Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (β=1.62, p=0.17), however, antidepressant adherence

  11. 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

  12. Modulation of muscarinic system with serotonin-norepinephrine reuptake inhibitor antidepressant attenuates depression in mice

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    Paramdeep Singh

    2015-01-01

    Full Text Available 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 < 0.0001 synergistic hyper-additive 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

  13. Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

    International Nuclear Information System (INIS)

    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 36Cl-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

  14. 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.

  15. Adherence to antidepressant medications: an evaluation of community pharmacists' counseling practices

    Directory of Open Access Journals (Sweden)

    Chong WW

    2013-08-01

    Full Text Available Wei Wen Chong,1,2 Parisa Aslani,1 Timothy F Chen1 1Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia; 2Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Recent studies have shown that pharmacists have a role in addressing antidepressant nonadherence. However, few studies have explored community pharmacists' actual counseling practices in response to antidepressant adherence-related issues at various phases of treatment. The purpose of this study was to evaluate counseling practices of community pharmacists in response to antidepressant adherence-related issues. Methods: A simulated patient method was used to evaluate pharmacist counseling practices in Sydney, Australia. Twenty community pharmacists received three simulated patient visits concerning antidepressant adherence-related scenarios at different phases of treatment: 1 patient receiving a first-time antidepressant prescription and hesitant to begin treatment; 2 patient perceiving lack of treatment efficacy for antidepressant after starting treatment for 2 weeks; and 3 patient wanting to discontinue antidepressant treatment after 3 months due to perceived symptom improvement. The interactions were recorded and analyzed to evaluate the content of consultations in terms of information gathering, information provision including key educational messages, and treatment recommendations. Results: There was variability among community pharmacists in terms of the extent and content of information gathered and provided. In scenario 1, while some key educational messages such as possible side effects and expected benefits from antidepressants were mentioned frequently, others such as the recommended length of treatment and adherence-related messages were rarely addressed. In all scenarios, about two thirds of pharmacists explored patients' concerns about antidepressant treatment. In scenarios 2 and 3, only half of all pharmacists

  16. Use of SSRI and SNRI Antidepressants during Pregnancy

    DEFF Research Database (Denmark)

    Zoega, Helga; Kieler, Helle; Nørgaard, Mette; Furu, Kari; Valdimarsdottir, Unnur; Brandt, Lena; Haglund, Bengt

    2015-01-01

    or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics. RESULTS: A total of 38 219 (3.3%) pregnancies......, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women....... women across four Nordic countries. METHODS: A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth...

  17. Thermodynamic properties of amphiphilic antidepressant drug citalopram HBr

    International Nuclear Information System (INIS)

    Association characteristics of antidepressant during Citalopram hydrobromide in water Have been examined and its thermodynamic parameters have been calculated using tensiometery and conductometry. The critical micelle concentration (cmc) was determined by surface tension measurement at 30 deg. C and Surface activity was studied by measuring surface parameters i.e. surface pressure, JI, surface excess concentration, area per molecule of drug and standard Gibbs free energy of adsorption, delta G. The electrical conductivity was measured as a function of concentration at various temperatures and cmc was calculated in the temperature range 20-50 deg. C. Thermodynamic parameters i.e. standard free energy of micellization, delta G standard enthalpy of micellization, delta H/sub m/ and standard entropy of micellization, delta S/sub m/ were calculated from cmc value using closed association model. (author)

  18. 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

    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...... double-blind, randomized, controlled trials. All patients completed a 5-week treatment period and fulfilled the DSM-III or DSM-III-R criteria for major depression. Clomipramine (150 mg/day) was the reference treatment, and comparable treatments were citalopram (40 mg/day), paroxetine (30 mg/day), and...... moclobemide (400 mg/day). Assessments were performed by using the 17-item Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. In a subgroup of 110 patients, weekly measurements of clomipramine plasma concentrations were obtained. Nonparametric statistical tests...

  19. [Comparative study of discriminative stimulus properties of antidepressants].

    Science.gov (United States)

    Korolev, A O; Kalinina, T S; Volkova, A V; Mokrov, G V; Kudriashov, N V; Voronina, T A

    2014-01-01

    Interoceptive stimulus properties of amitriptyline (54 mg/kg body weight), fluoxetine (10 mg/kg), and pyrrolo[1,2-a][1,4]diazepine derivative GMAL-24 (10 mg/kg) were studied in a standard operant model with liquid reinforcement of drug discrimination (DD) in male Wistar rats. A new experimental schedule that includes subchronic (7-day) administration of a training drug was used to perform DD learning. For the first time, it was found that amitriptyline has a discriminative interoceptive stimulus properties. Neither fluoxetine nor GMAL-24 did exhibit interoceptive properties. Imipramine (15 mg/kg, i.p.) fully substitutes for amitriptyline stimulus in substitution test. Fluoxetine (5 - 20 mg/kg, i.p.) failed to substitute with amitriptyline. Thus, amitriptyline/saline drug discrimination should be used for a comparative analysis of the central mechanisms of action of psychotropic substances, rather than for screening specific antidepressant activity. PMID:25322645

  20. Selective 5-HT2C agonists as potential antidepressants.

    Science.gov (United States)

    Leysen, D C

    1999-02-01

    The antidepressants currently used need improvement, especially in terms of efficacy, relapse rate and onset of action. In this review the clinical and experimental data which support the rationale for 5-HT2C agonists in the treatment of depression are listed. Next, the results obtained with the non-selective 5-HT2C agonists on the market and in clinical development are described. Finally, the preclinical data on the more selective 5-HT2C agonists are summarized. These recent preclinical results reveal a greater potency and effect size compared to fluoxetine, good tolerability and no evidence of tolerance development. Selective 5-HT2C agonists might become innovative drugs for the treatment of depression, panic, obsessive-compulsive disorder (OCD), some forms of aggression and eating disorders. PMID:16160946

  1. 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 ostatní: 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

  2. Acute antidepressant effects of intramuscular versus intravenous ketamine

    Directory of Open Access Journals (Sweden)

    Harihar Chilukuri

    2014-01-01

    Full Text Available Objective: Conventional antidepressants take two weeks before their therapeutic action begins. Recent studies have reported on the rapid antidepressant effect of ketamine when given as an intravenous (I.V. infusion. Little is known about its intramuscular (I.M. use in depression. Hence this study was conducted to compare the safety, tolerability and efficacy of I.M. versus. I.V. ketamine in Major Depression (ICD-10. Materials and Methods: It was a randomized open label parallel group study in a tertiary care teaching hospital. Study sample consisted of 27 subjects having major depression divided randomly into three groups of nine subjects each. Ketamine administered to each group in the dose of 0.5 mg/kg as an I.V. infusion, as 0.5 mg/kg I.M. or 0.25 mg/kg I.M. respectively. Depression rated on the Hamilton Depression Rating Scale (HAM-D before the injection, two hours later, the next day, and after three days. Data analyzed using the Statistical Package for Social Sciences (SPSS. Results: Mean age of the sample was 36.81 years (SD 11.815. Two hours after the injection, HAM-D fell by 58.86%, 60.29% & 57.36% in each group respectively. The improvement was sustained for next three days. Adverse effects noticed were rare, of mild nature and transient, lasting less than an hour. Conclusions: Intramuscular ketamine in the dose of 0.25 mg/kg is as effective and safe as 0.5 mg/kg given either I.M. or I.V., substantially alleviating depressive symptoms within a few hours and sustained for 3 days.

  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. Non-Antidepressant Psychopharmacologic Treatment of Specific Phobias.

    Science.gov (United States)

    Khalil, Rami Bou

    2013-02-01

    Specific phobias are among the most frequently diagnosed disorders in community with a twelve-month prevalence of 8.7% and a lifetime prevalence of 12.5%. Exposure-based therapies constitute the most effective treatment for this type of anxiety disorders. However, pharmacotherapies can still be considered for patients suffering from specific phobias in case they were non-adherent or resistant to exposure-based therapies or in case this kind of therapies was not accessible for them. Few data support the use of antidepressant in the treatment of specific phobias. A literature search via MedLine has been done in order to review all available studies in the domain of non-antidepressant pharmacotherapy of specific phobias. The importance of benzodiazepines such as diazepam, alprazolam and midazolam resides in the short-term reduction of subjective self-reported fear during the exposure to the feared object or situation. General anesthesia for the treatment of dental phobia does not seem to be efficient unless conducted with the inhalation anesthetic nitrous oxide which seems to be efficient on the short and on the long-term. Beta-adrenergic antagonists have been essayed with conflicting results. Cognitive enhancers such as D-cycloserine, glucocorticoids and yohimbine hydrochloride, seem to be more effective than placebo after a short term period of follow-up in treating specific phobia sympotms. In conclusion, promising efficient pharmacotherapies for specific phobias consists of drugs that enhance the efficacy of exposure-based therapies sessions by reducing anticipating phobia-related fear and/or by enhancing cognition during these sessions. PMID:23438730

  5. Antidepressant binding site in a bacterial homologue of neurotransmitter transporters.

    Science.gov (United States)

    Singh, Satinder K; Yamashita, Atsuko; Gouaux, Eric

    2007-08-23

    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 A 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 design of

  6. Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters

    International Nuclear Information System (INIS)

    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

  7. Signaling pathways regulating Homer1a expression: implications for antidepressant therapy.

    Science.gov (United States)

    Serchov, Tsvetan; Heumann, Rolf; van Calker, Dietrich; Biber, Knut

    2016-03-01

    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 mechanism for antidepressant therapy in general. However, the upstream signaling pathways that regulate or induce Homer1a expression are still not well understood. The main focus of the present review is to offer an overview of the current knowledge about the potential role of Homer1a in depression and the signaling pathways responsible for Homer1a regulation. It is suggested here that a detailed characterization of the signaling mechanisms leading to Homer1a expression might provide novel therapeutic targets for antidepressant drug development. PMID:26641965

  8. The unlicensed lives of antidepressants in India: generic drugs, unqualified practitioners, and floating prescriptions.

    Science.gov (United States)

    Ecks, Stefan; Basu, Soumita

    2009-03-01

    Antidepressant uses have been rising rapidly over the past decades. Two main theories have been advanced to explain this. One claims that socio-economic change causes a global rise of depressive illness. The other holds that European and North American corporations are aggressively marketing antidepressants to expand their global reach. Both theories assume that multinational capitalism drives rising depression rates. Based on ethnographic data from India, this article shows that antidepressants are increasingly used in this country as well, but for reasons than have been little explored yet. Taking fluoxetine (Prozac) as the main example, it is argued that the spread of antidepressants in India is ;unlicensed' by Euro-American corporations in at least three ways: (i) drug marketing is driven by Indian generic producers; (ii) fluoxetine is given by practitioners who have no license to do so; and (iii) knowledge of fluoxetine is spread through unlicensed ;floating' prescriptions that patients take from one prescriber to another. PMID:19293281

  9. Antidepressants for older people: what can we learn from the current evidence base?

    Science.gov (United States)

    Katona, Cornelius; Bindman, Dorothea C; Katona, Cara P

    2014-10-01

    This paper updates our previous review of the evidence base for managing depression in old age while focusing more specifically on the use of antidepressants. Overall, recent systematic reviews and meta-analyses indicate that antidepressants are effective in the acute treatment of depression in old age but that the superiority of active drug over placebo is quite modest. The depression of Alzheimer's disease is probably not treated effectively with antidepressants. The most consistent evidence is for the effectiveness of continued antidepressant treatment in those depressed patients who respond well to acute treatment. There remains a clear need for more research to identify effective treatments for resistant depression though therapeutic nihilism should be avoided if first-line treatment fails. PMID:24975955

  10. Inflammatory and Metabolic Dysregulation and the 2-Year Course of Depressive Disorders in Antidepressant Users

    NARCIS (Netherlands)

    Vogelzangs, Nicole; Beekman, Aartjan T. F.; Dortland, Arianne K. B. van Reedt; Schoevers, Robert A.; Giltay, Erik J.; de Jonge, Peter; Penninx, Brenda W. J. H.

    2014-01-01

    Scarce evidence suggests that inflammatory and metabolic dysregulation predicts poor response to antidepressants, which could result in worse depression outcome. This study prospectively examined whether inflammatory and metabolic dysregulation predicted the 2-year course of depressive disorders amo

  11. 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...... in relation to anxiety have given ambiguous results with both anxiolytic-like and anxiogenic-like effects observed after AMPAR blockade. This study systematically compared the effects of the AMPAR potentiator LY451646 and the AMPAR antagonist GYKI-53655 on depression-related behaviour using the mouse forced...... swim (FST) and tail suspension tests (TST), and anxiety-related behaviour using the elevated zero maze (EZM), marble burying (MB) and novelty-induced hypophagia (NIH) tests. The serotonin-selective antidepressant citalopram was included for comparison. Due to the importance of AMPARs in learning...

  12. Evaluation of antidepressant activity of ondansetron alone and in combination with fluoxetine-an experimental study

    Directory of Open Access Journals (Sweden)

    Sonal M. Parekar

    2016-02-01

    Conclusions: Our study concludes that ondansetron alone and in combination with fluoxetine possesses significant antidepressant activity in animal models of depression. [Int J Basic Clin Pharmacol 2016; 5(1.000: 90-97

  13. Evolution of the concepts of the molecular mechanism of the action of antidepressants (survey)

    International Nuclear Information System (INIS)

    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 [3H] WB 4101, [3H] LSD, and [3H] spiroperiodol (alpha1- and S2-receptors). Certain antidepressants also have a high affinity for the binding sites of [3H] clonidine and [3H] S (alpha2- and S1-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 [3H] LSD and [3H] spiroperiodol in the rat brain with high affinity and the binding of [3H] S with low affinity

  14. Effect of antidepressants and neuroleptics on phosphoinositide turnover in human platelets

    International Nuclear Information System (INIS)

    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

  15. The inhibition of phosphodiesterase type 5 as a novel target for antidepressant action

    DEFF Research Database (Denmark)

    Liebenberg, Nico

    2010-01-01

    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...... 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...

  16. Triiodothyronine augmentation for the treatment of depression in substance misusers unresponsive to tricyclic antidepressants

    OpenAIRE

    Kan, CK; Ho, TP

    2001-01-01

    We report on two substance misusers with depression resistant to tricyclic antidepressant treatment who responded to triiodothyronine augmentation. The management of resistant depression, augmentation strategies with particular reference to triiodothyronine, and the possible mechanism of action of triiodothyronine are discussed.

  17. Efficacy and safety of antidepressant's use in the treatment of depressive episodes in bipolar disorder - review of research.

    Science.gov (United States)

    Antosik-Wójcińska, Anna Zofia; Stefanowski, Bogdan; Święcicki, Łukasz

    2015-01-01

    The use of antidepressants in treatment of depression in course of bipolar disorders (BD) is controversial. In case of no improvement during monotherapy with mood stabilizer, the use of antidepressants is often necessary. The safety of this group (in context of phase change, mixed states and rapid cycling) is essential and is the subject of many research. In the paper, the authors review the literature concerning efficacy and safety of use of antidepressants in the treatment of affective disorders and long-term impact on the course of the disease. Selection of articles have been made by searching the Medline and Pubmed databases using keywords: antidepressant drugs, bipolar depression, bipolar disorder, efficacy, safety, mania, hypomania. The risk of mania is greater in bipolar disorder type I, than in type II or during treatment with Tricyclic antidepressants (TCAs) and treatment with venlafaxine. The use of SSRIs and bupropion is associated with a relatively small increase of phase change risk. There are different opinions concerning recommended duration of antidepressant treatment. Generally antidepressant use should end after 2-3 months of remission, the risk of recurrence of depression after discontinuation of antidepressants is, however, higher than in case of continuation. In BD type II or BD spectrum, antidepressant monotherapy is allowed in severe depression. In bipolar disorder type I and in case of phase change after antidepressants use in the past, use of antidepressants should be very cautious. Antidepressants are contraindicated in rapid cycling and in mixed episodes. Further work is needed to evaluate the efficacy and safety of antidepressants use. PMID:26909398

  18. 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

  19. Evaluation of Antidepressant-like Effect of Citrus Maxima Leaves in Animal Models of Depression

    OpenAIRE

    Potdar, Vikram H; Kibile, Swati J

    2011-01-01

    Objective(s) This study planned to assess antidepressant like activity of aqueous extract from leaves of Citrus maxima Merr. (Rutaceae). Materials and Methods Boiling was used for aqueous extraction. Acute toxicity study was performed in mice. Antidepressant activity was studied using locomotor activity test, modified forced swimming test (FST) and tail suspension test (TST). Three doses 100, 200 and 300 mg/kg of aqueous extract of leaves were selected for testing. Fluoxetine (20 mg/kg, i.p.)...

  20. 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.

  1. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    Science.gov (United States)

    Schultz, M.M.; Painter, M.M.; Bartell, S.E.; Logue, A.; Furlong, E.T.; Werner, S.L.; Schoenfuss, H.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 (Pimephales 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. ?? 2011 Elsevier B.V.

  2. Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats

    OpenAIRE

    Wibrand, Karin; Berge, Kjetil; Messaoudi, Michaël; Duffaud, Anaïs; Panja, Debabrata; Bramham, Clive R; Burri, Lena

    2013-01-01

    Background: The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats. Methods: Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance. Results: After 7 weeks of KO intake, both males and ...

  3. Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats

    OpenAIRE

    Wibrand, Karin; Berge, Kjetil; Messaoudi, Michaël; Duffaud, Anaïs; Panja, Debabrata; Bramham, Clive R; Burri, Lena

    2013-01-01

    Background The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats. Methods Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance. Results After 7 weeks of KO intake, both males and females t...

  4. Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

    OpenAIRE

    Elsbeth Jensen-Otsu; Austin, Gregory L.

    2015-01-01

    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 incl...

  5. Antidepressant-like Effect of Kaempferol and Quercitirin, Isolated from Opuntia ficus-indica var. saboten

    OpenAIRE

    Park, Soo-Hyun; Sim, Yun-Beom; Han, Pyung-Lim; Lee, Jin-Koo; Suh, Hong-Won

    2010-01-01

    Opuntia ficus-indica var. saboten. is widely cultivated in Jeju Island (South Korea) for use in manufacture of health foods. This study described antidepressant effect of two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. The expression of the hypothalamic POMC mRNA or plasma β-endorphin levels were increased by extract of Opuntia ficus-indica var. saboten or its flavoniods administered orally. In addition, antidepressant activity was studied using...

  6. Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

    OpenAIRE

    Løberg Else-Marie; Kroken Rune A; Jørgensen Hugo A; Kjelby Eirik; Johnsen Erik

    2011-01-01

    Abstract Background Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patient...

  7. Is the use of antidepressants associated with patient-reported outcomes following total hip replacement surgery?

    Science.gov (United States)

    Greene, Meridith E; Rolfson, Ola; Gordon, Max; Annerbrink, Kristina; Malchau, Henrik; Garellick, Göran

    2016-10-01

    Background and purpose - Patients with anxiety and/or depression tend to report less pain reduction and less satisfaction with surgical treatment. We hypothesized that the use of antidepressants would be correlated to patient-reported outcomes (PROs) 1 year after total hip replacement (THR), where increased dosage or discontinuation would be associated with worse outcomes. Patients and methods - THR cases with pre- and postoperative patient-reported outcome measures (PROMs) were selected from the Swedish Hip Arthroplasty Register (n = 9,092; women: n = 5,106). The PROMs were EQ-5D, visual analog scale (VAS) for pain, Charnley class, and VAS for satisfaction after surgery. These cases were merged with a national database of prescription purchases to determine the prevalence of antidepressant purchases. Regression analyses were performed where PROs were dependent variables and sex, age, Charnley class, preoperative pain, preoperative health-related quality of life (HRQoL), patient-reported anxiety/depression, and antidepressant use were independent variables. Results - Antidepressants were used by 10% of the cases (n = 943). Patients using antidepressants had poorer HRQoL and higher levels of pain before and after surgery and they experienced less satisfaction. Preoperative antidepressant use was independently associated with PROs 1 year after THR regardless of patient-reported anxiety/depression. Interpretation - Antidepressant usage before surgery was associated with reduced PROs after THR. Cases at risk of poorer outcomes may be identified through review of the patient's medical record. Clinicians are encouraged to screen for antidepressant use preoperatively, because their use may be associated with PROs after THR. PMID:27482877

  8. 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...

  9. Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study

    OpenAIRE

    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 tren...

  10. Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?

    OpenAIRE

    Cardamone, L.; Salzberg, MR; O'Brien, TJ; Jones, NC

    2013-01-01

    There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notabl...

  11. Social inequalities in antidepressant treatment and mortality: a longitudinal register study.

    OpenAIRE

    Kivimäki, M; Gunnell, D.; D.A. Lawlor; Davey Smith, G.; Pentti, J.; Virtanen, M; Elovainio, M; Klaukka, T; Vahtera, J.

    2007-01-01

    BACKGROUND: Despite an increased prevalence of depression among people of low socio-economic position, it remains unclear whether their treatment with antidepressants appropriately matches their increased need compared with people from more affluent backgrounds. This study examined socio-economic differences in antidepressant prescriptions and mortality related to depressive disorders. METHOD: A longitudinal register study of 17947 male and 47458 female local government employees with linked ...

  12. Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review

    OpenAIRE

    Nadeem Siddiqui; Andalip; Sandhya Bawa; Ruhi Ali; Obaid Afzal; M Jawaid Akhtar; Bishmillah Azad; Rajiv Kumar

    2011-01-01

    Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder...

  13. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Andersen, Jacob; Kristensen, Anders Skov; Bang-Andersen, Benny;

    2009-01-01

    The biogenic monoamine transporters are integral membrane proteins that perform active transport of extracellular dopamine, serotonin and norepinephrine into cells. These transporters are targets for therapeutic agents such as antidepressants, as well as addictive substances such as cocaine and...... antidepressant drugs that act on the serotonin and/or the norepinephrine transporters. Specifically, we focus on structure-activity relationships of these drugs with emphasis on relationships between their molecular properties and the current knowledge of transporter structure....

  14. The Food and Drug Administration’s Deliberations on Antidepressant Use in Pediatric Patients

    OpenAIRE

    Leslie, Laurel K.; Newman, Thomas B.; Chesney, P. Joan; Perrin, James M

    2005-01-01

    On February 2, 2004, the Food and Drug Administration organized a joint meeting of the Neuro-Psychopharmacologic Advisory Committee and Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee to examine the occurrence of suicidality in clinical trials that investigate the use of the newer anti-depressant drugs in pediatric patients. Committee members reconvened on September 13–14, 2004, and concluded that there was a causal link between the newer antidepressants and pediatric su...

  15. Prescribing Pattern of Antidepressant Drugs among General Practitioners and Psychiatrists: a study from Iran

    OpenAIRE

    Hamid Reza Motevallyzadeh; Mohammad Reza Baneshi; Maryam Rameshk; Nouzar Nakhaee

    2013-01-01

    Aim – This study was aimed to investigate the pattern of antidepressant drugs prescription among general practitioners and psychiatrists of Kerman/Iran with the goal of preventing irrational drug use. Methods – A total of 279737 prescriptions by general practitioners and psychiatrists of Kerman in 2010-2011 were reviewed. The frequency of antidepressant drugs prescription based on patients’ sex and age group (10-year age groups), the prescribed drug group and the prescriber (general practitio...

  16. Persistence and compliance to antidepressant treatment in patients with depression: A chart review

    Directory of Open Access Journals (Sweden)

    Sawada Norifusa

    2009-06-01

    Full Text Available Abstract Background Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not and compliance (i.e., whether patients take doses as instructed. However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10 (170 males; mean ± SD age 37.6 ± 13.9 years, who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR, defined as the total days a medication was dispensed to patients divided by the treatment period. Results Only 161 patients (44.3% continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride, and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14. An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8. Conclusion Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects.

  17. Use of antidepressant medications in relation to the incidence of breast cancer

    OpenAIRE

    Fulton-Kehoe, D; Rossing, M A; Rutter, C.; Mandelson, M T; Weiss, N S

    2006-01-01

    Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case–control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N=2904) and five controls were selected for each case (N=14396). Information on antidepressant use was ascertaine...

  18. Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures

    OpenAIRE

    Smaga, Irena; Bystrowska, Beata; Gawliński, Dawid; Pomierny, Bartosz; Stankowicz, Piotr; Filip, Małgorzata

    2014-01-01

    The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat...

  19. Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus.

    OpenAIRE

    Smith, M. A.; Makino, S.; Altemus, M; Michelson, D.; Hong, S. K.; Kvetnansky, R; Post, R. M.

    1995-01-01

    The mechanisms by which stress and anti-depressants exert opposite effects on the course of clinical depression are not known. However, potential candidates might include neurotrophic factors that regulate the development, plasticity, and survival of neurons. To explore this hypothesis, we examined the effects of stress and antidepressants on neurotrophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been implicate...

  20. Database processing for identification of concomitant drug frequencies in a forensic material positive for antidepressant drugs

    OpenAIRE

    Björn, Niklas

    2014-01-01

    This article presents a study conducted on data containing drug concentrations. The data was obtained from femoral venous blood samples collected at medico legal autopsies in Sweden. Cases positive for antidepressant drugs were scrutinized and divided in to two groups for 15 antidepressant drugs: B‑cases, where the cause of death was intoxication with more than one drug detected in the blood sample. C‑cases, where the cause of death was NOT intoxication and at least one drug (the antidepressa...

  1. Raphe-mediated signals control the hippocampal response to SRI antidepressants via miR-16

    OpenAIRE

    Launay, J. M.; Mouillet-Richard, S; Baudry, A.; Pietri, M; Kellermann, O.

    2011-01-01

    Serotonin reuptake inhibitor (SRI) antidepressants such as fluoxetine (Prozac), promote hippocampal neurogenesis. They also increase the levels of the bcl-2 protein, whose overexpression in transgenic mice enhances adult hippocampal neurogenesis. However, the mechanisms underlying SRI-mediated neurogenesis are unclear. Recently, we identified the microRNA miR-16 as an important effector of SRI antidepressant action in serotonergic raphe and noradrenergic locus coeruleus (LC). We show here tha...

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

    OpenAIRE

    Ioannidis John PA

    2008-01-01

    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-app...

  3. Neonatal Adaptation in Infants Prenatally Exposed to Antidepressants- Clinical Monitoring Using Neonatal Abstinence Score

    OpenAIRE

    Forsberg, Lisa; Navér, Lars; Lars L Gustafsson; Wide, Katarina

    2014-01-01

    Background Intrauterine exposure to antidepressants may lead to neonatal symptoms from the central nervous system, respiratory system and gastrointestinal system. Finnegan score (Neonatal Abstinence Score, NAS) has routinely been used to assess infants exposed to antidepressants in utero. Aim The purpose was to study neonatal maladaptation syndrome in infants exposed to selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI) in utero. Method Retro...

  4. 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.

  5. 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.

  6. "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. PMID:26498732

  7. Evaluation of Antidepressant activity of Simvastatin, Lovastatin and Atorvastatin in Male Swiss Mice - An Experimental Study

    Directory of Open Access Journals (Sweden)

    Gudadappanavar Anupama M

    2013-06-01

    Full Text Available Context: Depression is the commonest mood disorder, could also be secondary to a number of physical disorders. Pharmacological treatment of such co-morbidities is difficult. If statins show antidepressant activity that could appear to be better lipid-lowering agents as they provide additional benefits in cardiovascular disorders with co-morbidity like depression. Aims: To investigate the effect of simvastatin, lovastatin and atorvastatin for their antidepressant activity using forced swim test and tail suspension test on behavioral models of depression in male swiss mice. Design: Experimental Study Methods and Material: The in vivo antidepressant activity of simvastatin and lovastatin was studied using forced swim test and tail suspension test. The mice received the drug as per their weight and subjected for experimentation. Group mean immobility time was calculated in treated and control groups for comparison. Statistical analysis used: One-way analysis of variance (ANOVA followed by Bonferroni’s multiple comparison test. (P / 0.05 Results: Simvastatin and Lovastatin used in the present study showed significant antidepressant activity in both behavioral models of depression (p<0.05 while atorvastatin failed to show significant antidepressant action. Conclusion: The study suggests that the antidepressant activity of simvastatin and lovastatin, if could be extrapolated to clinical situations, appear to be better lipid-lowering agents as they provide additional benefits in cardiovascular disorders with co-morbidity like depression.

  8. Antidepressant-like activity of flunarizine in modified tail suspension test in rats

    Directory of Open Access Journals (Sweden)

    Vinod Shinde

    2015-01-01

    Full Text Available Background: Flunarizine, a Ca 2+ channel blocker, crosses blood brain barrier (BBB, antagonizes calcium influx and interferes with neurotransmitter system. Flunarizine 20 mg/kg exhibited significant antidepressant activity in our previous study using forced swim test (FST in mice, which was contradictory to the findings of other authors. Hence, the present study was designed to strengthen the results of our previous study, using the modified tail suspension test (TST in rats. Aim: Aim of this study was to evaluate the antidepressant activity of flunarizine versus standard antidepressant drug fluoxetine in modified TST in rats. Materials and Methods: The study approved by Institutional Animal Ethics Committee was conducted using 24 adult albino rats (n = 6 in each group. Antidepressant effect of normal saline (0.1 ml/100 g, fluoxetine (10 mg/kg, intraperitoneally (ip, and flunarizine (2 and 10 mg/kg, ip was evaluated by using modified TST in rats. Thirty minutes after administration of all test drugs the duration of immobility was recorded for a period of 5 min in all rats by using modified TST. The data was analyzed by Student′s t-test and one-way analysis of variance (ANOVA and P 0.05. Also, currently used human dose of flunarizine when extrapolated to rats (i. e., 2 mg/kg, ip failed to show significant antidepressant effect in modified TST in rats. Conclusion: The results of the present study indicate antidepressant-like activity of flunarizine.

  9. Antidepressant-like effects of Acorus calamus in forced swimming and tail suspension test in mice

    Institute of Scientific and Technical Information of China (English)

    Pawar Vinod S; Anup Akhade; Shrikrishna Baokar; Shivakumar H

    2011-01-01

    Objective: To evaluate the antidepressant activity of methanolic extract of rhizomes of Acoruscalamus (A. calamus). Methods: Tail suspension test (TST) and forced swimming test (FST) in mice were used to evaluate the antidepressant activity of methanolic extract of rhizomes of A. calamus. Methanolic extracts (50 and 100 mg/kg i.p.) were administered daily for 7 days. Imipramine 5 mg/kg was used as standard antidepressant agent throughout the study. Results: Test extracts of A. calamus decreased immobility periods significantly in a dose dependent manner in both TST and FST. The observed results were also comparable with known standard drug i.e. imipramine. The flavonoid apigenin, which selectively binds with high affinity to the central benzodiazepines receptor, possesses important anxiolytic and antidepressant activities. The review of literature reveals that the A. calamus contains saponin, glycosides, tannin and flavonoid. Conclusions:Methanolic extract of A. calamus rhizomes shows antidepressant activity probably through interaction with adrenergic, dopaminergic serotonergic and γ-aminobutyric acid (GABA) nergic system. Both the models have been proved to be equally valuable for demonstration of substances with a potential antidepressant activity.

  10. The effects of antenatal depression and antidepressant treatment on placental gene expression

    Directory of Open Access Journals (Sweden)

    Jocelien DA Olivier

    2015-01-01

    In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

  11. Antidepressant Prescription Claims Among Reproductive-Aged Women With Private Employer-Sponsored Insurance - United States 2008-2013.

    Science.gov (United States)

    Dawson, April L; Ailes, Elizabeth C; Gilboa, Suzanne M; Simeone, Regina M; Lind, Jennifer N; Farr, Sherry L; Broussard, Cheryl S; Reefhuis, Jennita; Carrino, Gerrard; Biermann, Janis; Honein, Margaret A

    2016-01-01

    Antidepressant medication use during pregnancy has been increasing in the United States (1). Many women require antidepressants on an ongoing basis, and a clear consensus on the safest medication options for both the mother and her fetus does not exist (2). Given that half of all U.S. pregnancies are unplanned (3), antidepressant use will occur during the first weeks of pregnancy, a critical period for fetal development. To understand trends among women of reproductive age, CDC used Truven Health's MarketScan Commercial Claims and Encounters data* to estimate the number of antidepressant prescriptions filled by women aged 15-44 years with private employer-sponsored insurance. During 2008-2013, an average of 15.4% of women aged 15-44 years filled at least one prescription for an antidepressant in a single year. The most frequently filled antidepressants included sertraline, bupropion, and citalopram. Prescribing of antidepressants is common, and research on antidepressant safety during pregnancy needs to be accelerated to provide evidence-based information to health care providers and women about the potential risks for antidepressant exposure before and during pregnancy and between pregnancies. PMID:26821271

  12. Tricyclic Neovibsanin Scaffold (TCNS) as an Effective Antidepressant Agent.

    Science.gov (United States)

    Qiao, D-D; Mi, G-L; Tang, M-Q

    2016-02-01

    Neovibsanin type natural products were found to display neurite outgrowth activity in PC12 cells. This suggests that such type of compounds could be promising candidates for the development of novel therapeutic agents to treat neurological diseases. In the present study rats after chronic mild stress (CMS) were treated with tricyclic neovibsanin scaffold (TCNS) to study its effect on depression. The results revealed that 15 mg/kg doses of TCNS reduced the duration of immobility in CMS model of depression. It led to a significant increase in neurite outgrowths which increased the synaptic and structural plasticity of neurons. Treatment with TCNS decreased the levels of MAO-A and caspase-3 expression both of which were found to be higher in CMS. TCNS also led to an increase in expression of heat shock protein 70 (Hsp70) in the hippocampus. These findings suggest that TCNS possesses antidepressant activity in CMS model of depression. Therefore the relief in depression by TCNS may be due to suppression of MAO-A expression and the apoptosis cascade by increased expression of Hsp70. PMID:25823508

  13. Subcellular localization of the antidepressant-sensitive norepinephrine transporter

    Directory of Open Access Journals (Sweden)

    Winder Danny G

    2009-06-01

    Full Text Available Abstract Background Reuptake of synaptic norepinephrine (NE via the antidepressant-sensitive NE transporter (NET supports efficient noradrenergic signaling and presynaptic NE homeostasis. Limited, and somewhat contradictory, information currently describes the axonal transport and localization of NET in neurons. Results We elucidate NET localization in brain and superior cervical ganglion (SCG neurons, aided by a new NET monoclonal antibody, subcellular immunoisolation techniques and quantitative immunofluorescence approaches. We present evidence that axonal NET extensively colocalizes with syntaxin 1A, and to a limited degree with SCAMP2 and synaptophysin. Intracellular NET in SCG axons and boutons also quantitatively segregates from the vesicular monoamine transporter 2 (VMAT2, findings corroborated by organelle isolation studies. At the surface of SCG boutons, NET resides in both lipid raft and non-lipid raft subdomains and colocalizes with syntaxin 1A. Conclusion Our findings support the hypothesis that SCG NET is segregated prior to transport from the cell body from proteins comprising large dense core vesicles. Once localized to presynaptic boutons, NET does not recycle via VMAT2-positive, small dense core vesicles. Finally, once NET reaches presynaptic plasma membranes, the transporter localizes to syntaxin 1A-rich plasma membrane domains, with a portion found in cholera toxin-demarcated lipid rafts. Our findings indicate that activity-dependent insertion of NET into the SCG plasma membrane derives from vesicles distinct from those that deliver NE. Moreover, NET is localized in presynaptic membranes in a manner that can take advantage of regulatory processes targeting lipid raft subdomains.

  14. The radioimmunoassay of clomipramine (Anafranil-Geigy). A tricyclic antidepressant

    International Nuclear Information System (INIS)

    A radioimmunoassay has been developed for the tricyclic antidepressant, clomipramine (Anafranil-Geigy) which allows accurate determination of plasma levels without a pre-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 didesmethylclomipramine <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 GC or GC/MS 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 a week per technician), make the assay ideal for supervision of patient compliance and routine assay of samples generated in large clinical trials. (author)

  15. Hippocampal VEGF is necessary for antidepressant-like behaviors but not sufficient for antidepressant-like effects of ketamine in rats.

    Science.gov (United States)

    Choi, Miyeon; Lee, Seung Hoon; Chang, Ho Lee; Son, Hyeon

    2016-07-01

    We investigated the effects of ketamine on both the temporal and spatial profiles of neural precursor cells located in the hippocampus, and on antidepressant-like behaviors in rats. A single dose of ketamine resulted in a significant increase in the number of 5-bromo-2-deoxyuridine-positive (BrdU(+)) cells in the dentate gyrus (DG) of rats at 24h, but not at 28days, after treatment completion. Ketamine caused antidepressant-like behaviors in the forced swim test (FST) and novelty suppressed feeding test (NSFT). Viral-mediated hippocampal knockdown of vascular endothelial growth factor (VEGF) produced depressive-like behaviors in the FST and NSFT, which were partially recovered by ketamine to the level observed in the control group. The behavioral effects of VEGF knock down were accompanied by a decrease in hippocampal neurogenesis, which was also partially recovered by ketamine. Our results suggest that basal hippocampal VEGF expression is necessary for ketamine-induced antidepressant-like behaviors in rats, but ketamine-induced VEGF expression only partially contributes to hippocampal neurogenesis and the antidepressant-like effects of ketamine. PMID:27063455

  16. Orchiectomy modifies the antidepressant-like response of nicotine in the forced swimming test.

    Science.gov (United States)

    Bonilla-Jaime, H; Limón-Morales, O; Arteaga-Silva, M; Hernández-González, M; Guadarrama-Cruz, G; Alarcón-Aguilar, F; Vázquez-Palacios, G

    2010-11-01

    Several studies have demonstrated that nicotine (NIC) exhibits antidepressant-like effects. In addition, it has been suggested that sexual hormones participate in the antidepressant actions of antidepressives. The present study was designed to analyze the effect of orchiectomy and the supplementation of testosterone propionate (TP) or 17β-estradiol (E(2)) on the antidepressant properties of NIC using the forced swimming test (FST), as well as to determine possible changes in the FST during different time periods after orchiectomy. In order to evaluate the influences of orchiectomy on the effects of NIC, the study first evaluated the effects of different time periods on orchiectomized rats (15, 21, 30, 45 and 60 days) that were subjected to the FST. Then, different doses of NIC (0.2, 0.4, 0.8, 1.6 mg/kg, sc) were administered for 14 days to both intact and orchiectomized rats (after 21 day) which were then also subjected to the FST. Finally, the influence of the TP or E(2) supplementation on the antidepressant-like effect of NIC on orchiectomized rats (after 21 days) was also analyzed. Results reveal that orchiectomy significantly increased immobility behavior and decreased swimming and climbing up to 60 days after castration. In contrast, NIC decreased immobility behavior and increased swimming in intact rats; whereas orchiectomy suppressed this antidepressant effect of NIC. Only with E(2) supplementation was it possible to restore the sensitivity of the castrated rats to NIC. These results suggest that E(2) was able to facilitate the antidepressant response of NIC in orchiectomized rats. PMID:20709090

  17. The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2008-01-01

    Full Text Available 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 antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

  18. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant.

    Science.gov (United States)

    Patel, Krisna; Allen, Sophie; Haque, Mariam N; Angelescu, Ilinca; Baumeister, David; Tracy, Derek K

    2016-04-01

    Bupropion has been used as an antidepressant for over 20 years, though its licence for such use varies and it is typically a third- or fourth-line agent. It has a unique pharmacology, inhibiting the reuptake of noradrenaline and dopamine, potentially providing pharmacological augmentation to more common antidepressants such as selective serotonergic reuptake inhibitors (SSRIs). This systematic review and meta-analysis identified 51 studies, dividing into four categories: bupropion as a sole antidepressant, bupropion coprescribed with another antidepressant, bupropion in 'other' populations (e.g. bipolar depression, elderly populations) and primary evaluation of side effects. Methodologically more robust trials support the superiority of bupropion over placebo, and most head-to-head antidepressant trials showed an equivalent effectiveness, though some of these are hindered by a lack of a placebo arm. Most work on the coprescribing of bupropion with another antidepressant supports an additional effect, though many are open-label trials. Several large multi-medication trials, most notably STAR*D, also support a therapeutic role for bupropion; in general, it demonstrated similar effectiveness to other medications, though this literature highlights the generally low response rates in refractory cohorts. Effectiveness has been shown in 'other' populations, though there is an overall dearth of research. Bupropion is generally well tolerated, it has very low rates of sexual dysfunction, and is more likely to cause weight loss than gain. Our findings support the use of bupropion as a sole or coprescribed antidepressant, particularly if weight gain or sexual dysfunction are, or are likely to be, significant problems. However there are notable gaps in the literature, including less information on treatment naïve and first presentation depression, particularly when one considers the ever-reducing rates of response in more refractory illness. There are some data to support

  19. Is increased antidepressant exposure a contributory factor to the obesity pandemic?

    Science.gov (United States)

    Lee, S H; Paz-Filho, G; Mastronardi, C; Licinio, J; Wong, M-L

    2016-01-01

    Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic-pituitary-adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of

  20. Is increased antidepressant exposure a contributory factor to the obesity pandemic?

    Science.gov (United States)

    Lee, S H; Paz-Filho, G; Mastronardi, C; Licinio, J; Wong, M-L

    2016-01-01

    Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination

  1. The mesolimbic dopamine system as a target for rapid antidepressant action.

    Science.gov (United States)

    Willner, P

    1997-07-01

    Chronic treatment with antidepressant drugs produces a variety of changes in dopaminergic neurotransmission, most notably a sensitization of behavioural responses to agonists acting at dopamine D2/D3 receptors within the nucleus accumbens. Evidence from animal models of depression (the forced swim test and the chronic mild stress procedure) indicates that these effects are crucial for the therapeutic effect of antidepressants in these models. Antidepressant-like effects in animal models are also seen with drugs that act directly on the dopaminergic system. Because of its prolonged time-course, the chronic mild stress procedure can be used to examine onset latencies. Some dopamine-active drugs (e.g. the catechol-O-methyltransferase inhibitor tolcapone; D2/D3 agonists administered intermittently) are active in this procedure but have a time-course comparable to that of conventional antidepressants. Other dopamine-active drugs may have a more rapid onset; the evidence to date suggests this possibility for the D2/D3 agonist pramipexole and the preferential presynaptic antagonist amisulpride. In clinical studies, rapid-onset latencies have been claimed for the D2/D3 agonist roxindole, the preferential presynaptic antagonist sulpiride and the relatively selective dopamine-uptake inhibitor amineptine. The mechanisms that might give rise to a rapid onset of dopamine-mediated antidepressant effects are discussed. PMID:9347387

  2. Identification of primary care patients at risk of nonadherence to antidepressant treatment

    Directory of Open Access Journals (Sweden)

    Ann-Charlotte Åkerblad

    2009-01-01

    Full Text Available Ann-Charlotte Åkerblad1, Finn Bengtsson2, Margareta Holgersson3, Lars von Knorring1, Lisa Ekselius11Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala University, Uppsala, Sweden; 2Division of Clinical Pharmacology, Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 3Quintiles AB, Uppsala, SwedenIntroduction: Poor adherence to antidepressant treatment is common, and results in increased disability and costs. Several factors are thought to influence patients’ ability and willingness to adhere. So far, however, consensus is lacking regarding patient characteristics that predict nonadherence. The purpose of this study was to identify predictors of nonadherence to antidepressant treatment that can be ascertained at treatment start.Method: The present study used data from a randomized controlled trial with the main objective of studying the effect of two different compliance-enhancing programs on treatment adherence and treatment response in 1031 primary care patients with major depression. In this study, logistic regression analyses were performed to examine patient- and illness-related characteristics potentially associated with nonadherence.Results: Nonadherence to antidepressant treatment was predicted by age under 35 or over 64 years, presence of personality disorder, sensation-seeking personality traits, substance abuse, and absence of concomitant medications.Conclusion: Certain patient- and illness-related characteristics may imply an increased risk of nonadherence to antidepressant treatment. Giving special attention to subjects with such characteristics may improve adherence.Keywords: unipolar depression, antidepressant, adherence, compliance, SSRI, predictors

  3. [Use of antidepressants in the treatment of negative symptoms of schizophrenia].

    Science.gov (United States)

    Palomba, A; Lodovighi, M-A; Belzeaux, R; Adida, M; Azorin, J-M

    2015-12-01

    Negative symptoms account for a clinical dimension of schizophrenia. They are partly the cause of functional disability of this disease. Clinical experience shows that antipsychotics have little or no effect on these symptoms. The aim of this review is to gather existing data on the treatment of negative symptoms with antidepressants. The combination of antipsychotics with antidepressants is a therapeutic strategy commonly used for the treatment of these symptoms. The pro-dopaminergic effects of antidepressants explain their effectiveness on negative symptoms. There are many comparative, randomized, controlled studies evaluating the efficacy of antidepressant associated with antipsychotic for the treatment of negative symptoms. Furthermore three meta-analyses have been conducted. The overall results suggest that the use of antidepressants may contribute to clinical improvement of negative symptoms in schizophrenia. The limitations of these studies are the small number of patients included and the definition and assessment of negative symptoms. The existing scales are not sufficiently discriminating. Further research using new measurement tools should help refine these results. PMID:26776391

  4. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID-ACTING ANTIDEPRESSANTS.

    Science.gov (United States)

    Abdallah, Chadi G; Adams, Thomas G; Kelmendi, Benjamin; Esterlis, Irina; Sanacora, Gerard; Krystal, John H

    2016-08-01

    Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last 20 years due to the discovery that a single subanesthetic dose leads to a rapid antidepressant effect in individuals with treatment-resistant depression. Animal and human research suggest that ketamine's antidepressant effects are mediated by a glutamate surge that leads to a cascade of events that result in synaptogenesis and reversal of the negative effects of chronic stress and depression, particularly within the prefrontal cortex (PFC). Preclinical and clinical data have provided compelling insights into the mechanisms underlying the rapid-acting antidepressant effects of ketamine. This review discusses stress-related neurobiology of depression and the safety, tolerability, and efficacy of ketamine for MDD, along with a review of ketamine's mechanism of action and prospective predictors of treatment response. Research limitations and future clinical prospects are also discussed. PMID:27062302

  5. Antidepressant Effects of AMPA and Ketamine Combination: Role of Hippocampal BDNF, Synapsin, and mTOR

    Science.gov (United States)

    Akinfiresoye, Luli; Tizabi, Yousef

    2013-01-01

    Rationale A number of preclinical and clinical studies suggest ketamine, a glutamate NMDA (N-methyl-D-aspartate) receptor antagonist, has a rapid and lasting antidepressant effect when administered either acutely or chronically. It has been postulated that this effect is due to stimulation of AMPA (alpha-amino-3-hydroxy-5-methyl–4-isoxazolepropionic acid) receptors. Objective In this study, we tested whether AMPA alone has an antidepressant effect and if the combination of AMPA and ketamine provides added benefit in Wistar-Kyoto (WKY) rats, a putative animal model of depression. Results Chronic AMPA treatment resulted in a dose dependent antidepressant effect in both the forced swim test (FST) and sucrose preference test. Moreover, chronic administration (10–11d) of combinations of AMPA and ketamine, at doses that were ineffective on their own, resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain derived neurotrophic factor (BDNF), synapsin, and mammalian target of rapamycin (mTOR). Conclusion These findings are the first to provide evidence for an antidepressant effect of AMPA, and suggest the usefulness of AMPA-ketamine combination in treatment of depression. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis and synaptogenesis, suggesting a mechanism of their action. PMID:23732839

  6. Potential antidepressant-like properties of the TC G-1008, a GPR39 (zinc receptor) agonist.

    Science.gov (United States)

    Młyniec, Katarzyna; Starowicz, Gabriela; Gaweł, Magdalena; Frąckiewicz, Ewelina; Nowak, Gabriel

    2016-09-01

    Some forms of depression appear to be more related to the glutamatergic system. G-coupled protein receptor 39 (GPR39) is the metabotropic zinc receptor, which may be involved in the pathophysiology of depression and in the antidepressant response. Its deficiency abolishes the antidepressant response, which means that GPR39 is required to obtain a therapeutic effect in depression. This raises the possibility that agonists of the zinc receptor may have a role in antidepressant treatment. To explore this possibility we investigated animal behaviour in the forced swim test, the tail suspension test (to assess antidepressant-like properties), the light/dark test and the elevated plus maze test (to assess anxiolytic-like properties), following acute administration of a GPR39 agonist (TC G-1008). We found an antidepressant response (as measured by the forced swim test but not by the tail suspension test) in mice following the GPR39 agonist treatment. Additionally, we observed the opposite results in the light/dark box (decreased overall distance; increased time spent in the lit compartment; decreased time spent in the dark compartment; increased freezing time) and elevated plus maze (no significant changes), which may be a consequence of the sedative effect of TC G-1008. We also found hippocampal GPR39 and brain-derived neurotrophic factor (BDNF) up-regulation following administration of the GPR39 agonist, which may be undiscovered so far as a possible novel agent in the treatment of mood disorders. PMID:27235821

  7. Drug use pattern of antidepressant agents in psychiatric patients – A prospective study

    Directory of Open Access Journals (Sweden)

    Aksha Memon

    2013-07-01

    Full Text Available Background: Depression is a major public health problem. It causes clinically significant distress, impairment of social, occupational or other important areas of function. Objective: To evaluate the prescribing pattern of antidepressant agents in patients attending psychiatry OPD at a tertiary care teaching hospital. Method: A prospective study was carried out at psychiatry outpatient department (OPD at VS General Hospital for 6 months. Patients who were prescribed any of the antidepressant medications irrespective of clinical indication either as monotherapy or in combination with other psychotherapeutic agents were included in the study. Result: Total 455 patients were enrolled for 6 months. Major Depressive Disorder (MDD was the most common diagnosis (85.93%. Tricyclic antidepressants (TCAs was the most commonly prescribed drug group (56.7% followed by selective serotonin reuptake inhibitors (SSRIs (46.8%. Amongst TCAs, imipramine was most frequently prescribed drug (65.89% followed by sertraline (56.8% among the SSRIs. Both the TCAs and newer antidepressants were prescribed with equal frequencies. Conclusion: Amongst antidepressants most frequently prescribed medication was imipramine followed by sertraline.

  8. Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy

    Directory of Open Access Journals (Sweden)

    Paul R Albert

    2010-06-01

    Full Text Available Major depression is the most common form of mental illness, and is treated with antidepressant compounds that increase serotonin (5-HT neurotransmission. Increased 5-HT1A autoreceptor levels in the raphe nuclei act as a “brake” to inhibit the 5-HT system, leading to depression and resistance to antidepressants. Several 5-HT1A receptor agonists (buspirone, flesinoxan, ipsapirone that preferentially desensitize 5-HT1A autoreceptors have been tested for augmentation of antidepressant drugs with mixed results. One explanation could be the presence of the C(-1019G 5-HT1A promoter polymorphism that prevents gene repression of the 5-HT1A autoreceptor. Furthermore, down-regulation of 5-HT1A autoreceptor expression, not simply desensitization of receptor signaling, appears to be required to enhance and accelerate antidepressant action. The current review focuses on the transcriptional regulators of 5-HT1A autoreceptor expression, their roles in permitting response to 5-HT1A-targeted treatments and their potential as targets for new antidepressant compounds for treatment-resistant depression.

  9. [Antidepressant-resistant depression and bipolar spectrum - diagnostic and therapeutic considerations].

    Science.gov (United States)

    Rihmer, Zoltán; Gonda, Xénia; Rihmer, Annamária; Döme, Péter

    2016-01-01

    According to the results of epidemiological studies mood disorders with unipolar (major and minor depressive disorder; dysthymia) or bipolar features are among the most prevalent psychiatric disorders. These disorders with their frequent comorbidities (alcohol and/or drug use disorders, smoking, suicide, cardiovascular disorders) pose great public health challenge and cause substantial individual and familar burdens as well. Since SSRIs and other new antidepressant agents entered the market the possibilities to treat depression improved substantially but 25-35 percent of major depressives do not respond even to the second antidepressant trial but the rate of patients who are resistant after the third and fourth adequate antidepressant trial are around only 15-25 and 10 percent, respectively. Pharmacotherapy-resistant depression is a multicausal phenomenon. Along with its well-known risk-factors investigations of the past decade have revealed that unrecognised or hidden (subsyndromal or subthreshold) bipolarity is one of the most frequent causes of treatment resistance. In the case of bipolar depression (either as a part of syndromal bipolar I or II disorder or a subsyndromal manifestation) antidepressant monotherapy should be avoided and, instead of it, the administration of a mood stabilizer (primarily lithium and lamotrigine) or some atypical antipsychotics (preferably quetiapine) are recommended. If antidepressant is inevitably necessary in bipolar depression, we should use it always in combination with mood stabilizers or atypical antipsychotics. PMID:27244871

  10. Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

    KAUST Repository

    Martin, Jean Luc

    2013-09-01

    There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

  11. The sedating antidepressant trazodone impairs sleep-dependent cortical plasticity.

    Directory of Open Access Journals (Sweden)

    Sara J Aton

    Full Text Available BACKGROUND: Recent findings indicate that certain classes of hypnotics that target GABA(A receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABA(A receptor agonists zaleplon and eszopiclone in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1 known as ocular dominance plasticity. METHODOLOGY/PRINCIPAL FINDINGS: After a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg, zaleplon (10 mg/kg, or eszopiclone (1-10 mg/kg, and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG activity, only trazodone (which did not alter EEG activity significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions.

  12. Antidepressant therapies inhibit inflammation and microglial M1-polarization.

    Science.gov (United States)

    Kalkman, Hans O; Feuerbach, Dominik

    2016-07-01

    Macrophages and their counterparts in the central nervous system, the microglia, detect and subsequently clear microbial pathogens and injured tissue. These phagocytic cells alter and adapt their phenotype depending on their prime activity, i.e., whether they participate in acute defence against pathogenic organisms ('M1'-phenotype) or in clearing damaged tissues and performing repair activities ('M2'-phenotype). Stimulation of pattern recognition receptors by viruses (vaccines), bacterial membrane components (e.g., LPS), alcohol, or long-chain saturated fatty acids promotes M1-polarization. Vaccine or LPS administration to healthy human subjects can result in sickness symptoms and low mood. Alcohol abuse and abdominal obesity are recognized as risk factors for depression. In the M1-polarized form, microglia and macrophages generate reactive oxygen and nitrogen radicals to eradicate microbial pathogens. Inadvertently, also tetrahydrobiopterin (BH4) may become oxidized. This is an irreversible reaction that generates neopterin, a recognized biomarker for depression. BH4 is a critical cofactor for the synthesis of dopamine, noradrenaline, and serotonin, and its loss could explain some of the symptoms of depression. Based on these aspects, the suppression of M1-polarization would limit the inadvertent catabolism of BH4. In the current review, we evaluate the evidence that antidepressant treatments (monoamine reuptake inhibitors, PDE4 inhibitors, lithium, valproate, agomelatine, tianeptine, electroconvulsive shock, and vagus nerve stimulation) inhibit LPS-induced microglia/macrophage M1-polarization. Consequently, we propose that supplementation with BH4 could limit the reduction in central monoamine synthesis and might represent an effective treatment for depressed mood. PMID:27101921

  13. Antidepressant use and risk for mortality in 121,252 heart failure patients with or without a diagnosis of clinical depression

    DEFF Research Database (Denmark)

    Brouwers, Corline; Christensen, Stefan B; Damen, Nikki L; Denollet, Johan; Torp-Pedersen, Christian; Gislason, Gunnar H; Pedersen, Susanne S

    2016-01-01

    clinical depression were independently associated with antidepressant use. Patients using no antidepressants with clinical depression and patients using antidepressants, with or without clinical depression, had a significantly higher risk for all-cause mortality (HR, 1.25; 95% CI, 1.15-1.36; HR, 1.24; 95....... CONCLUSION: Patients with HF taking antidepressants had an increased risk for all-cause and CV-mortality, irrespectively of having clinical depression. These results highlight the importance of further examining the antidepressant prescription pattern in patients with HF, as this may be crucial in......BACKGROUND: Depression is a risk factor for mortality in patients with heart failure (HF), however, treating depression with antidepressant therapy does not seem to improve survival. We examined the prevalence of antidepressant use in HF patients, the correlates of antidepressant use subsequent to...

  14. Rapid Antidepressant Changes with Sleep Deprivation in Major Depressive Disorder are Associated with Changes in Vascular Endothelial Growth Factor (VEGF): a Pilot Study

    OpenAIRE

    Ibrahim, Lobna; Duncan, Wallace; Luckenbaugh, David A.; Yuan, Peixiong; Machado-Vieira, Rodrigo; Carlos A Zarate

    2011-01-01

    While conventional antidepressants benefit many patients with major depressive disorder (MDD), as much as eight to 12 weeks can elapse before significant improvements in depressive symptoms are seen. Treatments that act more rapidly in MDD are urgently needed. Sleep deprivation (SD) has been shown to produce a rapid antidepressant response within one day in 50–60% of patients with MDD; thus, identifying its antidepressant mechanism may contribute to the development of antidepressants that act...

  15. Design, Synthesis, and Potential Antidepressant-like Activity of 7-prenyloxy-2,3-dihydroflavanone Derivatives.

    Science.gov (United States)

    Zhen, Xing-Hua; Quan, Ying-Chun; Peng, Zhou; Han, Yan; Zheng, Zhou-Jun; Guan, Li-Ping

    2016-06-01

    A series of 7-prenyloxy-2, 3-dihydroflavanone derivatives were synthesized and screened for their antidepressant-like activity. Among them, it was observed that compounds 5j and 5k were found to be the most antidepressant-like activity. In addition, it was found that compounds 5j and 5k significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus, and cortex. Compounds 5j and 5k also significantly increased the contents of 5-HIAA in the hippocampus and cortex, shut down 5-HT metabolism compared with mice treated with stress vehicle. These results suggested that compounds 5j and 5k displayed potent antidepressant-like properties that were mediated via neurochemical systems. PMID:26705885

  16. Is nitric oxide signalling involved in the antidepressant action of ketamine?

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina;

    2012-01-01

    Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect in...... depressed patients following a single intravenous administration that is sustained for ± 7 days. A number of downstream cellular mechanisms appear to mediate the antidepressant action of ketamine, and the majority of evidence point to a rapid activation of protein translation leading to increased synaptic...... receptors, while the uncoupling of the nNOS-NMDA receptor complex prevents NMDA-induced excitotoxicity. Thus, it is possible that the inhibition of nitric oxide (NO) signalling underlies a key upstream mechanism in the antidepressant action of ketamine. Methods: We used a genetic rat model of depression...

  17. [Antidepressants and their onset of action: a major clinical, methodological and pronostical issue].

    Science.gov (United States)

    Gourion, D

    2008-01-01

    Although antidepressant medications are effective in about 50-70% of patients with major depressive disorder (MDD), they have a delayed onset of therapeutic effect. This latency is one of the current major limitations of these medications, in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. It is becoming increasingly clear that differences may exist between antidepressants and some evidence suggests that some antidepressant agents may begin to work faster than others. Escitalopram, duloxetine, venlafaxine, and mirtazapine have shown statistically significant differences in some measures of antidepressant action within the first two weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. Results of the current review should be regarded with certain important limitations in mind. First, differences in times to onset of antidepressant response have been shown in clinical efficacy studies not specifically designed to detect differences in onset of action (post-hoc analysis). Second, results observed in 'pure' clinical trial samples should not be directly generalized to the real clinical practice since it has been proven in clinical settings that less than one in seven depressed patients would be eligible to participate in antidepressant clinical trials. For instance, depressed patients who are suicidal or who score higher than 30 on the 17-item HAM-D are excluded from antidepressant clinical trials. Third, caution is warranted when applying these findings to clinical populations with more severe depressions with respect to the fact that among clinical populations, severity of depression coincides with comorbidity, including such psychiatric disorders as anxiety disorders, personality disorders and

  18. Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

    Directory of Open Access Journals (Sweden)

    Jian-hua Liu

    2012-01-01

    Full Text Available Adenylyl cyclase (AC-cyclic adenosine monophosphate (cAMP-cAMP-dependent protein kinase A (PKA cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA treatment for chronic mild stress (CMS-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.

  19. Treating depression with antidepressants: drug-placebo efficacy debates limit broader considerations.

    Science.gov (United States)

    Yapko, Michael D

    2013-01-01

    The core issue regarding antidepressants for many clinicians is whether they perform significantly better than placebos. However, this article suggests eight additional concerns beyond drug efficacy alone to consider regarding antidepressants including: (1) formulating only a one-dimensional, biological view of depression; (2) defining the client's role as passive in treatment; (3) economic corruption of the research and reporting; (4) false or misleading consumer advertising; (5) conflicting data that confuse practitioners and consumers alike; (6) over- and under-prescription of medications; (7) drug side-effects; and (8) harm to the environment. The enhanced effects of psychotherapy utilizing hypnosis offer a means of avoiding most, if not all, of the problems associated with the use of antidepressants as a primary form of treatment. PMID:23488253

  20. GPR39 Zn(2+)-sensing receptor -a new target in antidepressant development?

    DEFF Research Database (Denmark)

    Młyniec, Katarzyna; Singewald, Nicolas; Holst, Birgitte; Nowak, Gabriel

    2015-01-01

    exhibits an antidepressant-like profile, as demonstrated in both preclinical and clinical studies. Recent reports indicate that the GPR39 Zn(2+)-sensing receptor is an important target for zinc "transmission" (its activation modulates/induces diverse biochemical pathways involved in neuroprotection......). Preclinical studies provide evidence that zinc deficiency leads to depressive-like behavior related to down-regulation of the GPR39 Zn(2+)-sensing receptor. Zinc binds to the GPR39 and triggers signals, leading to CRE-dependent gene transcription, resulting in increases in proteins such as brain......-derived neurotrophic factor (BDNF), that plays a pivotal role in antidepressant action. Chronic administration of many antidepressants induces GPR39 up-regulation, which suggests that the Zn(2+)-sensing receptor may be considered as a new target for drug development in the field of depression....

  1. Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of a frequent interaction in the elderly.

    Science.gov (United States)

    Govoni, S; Racchi, M; Masoero, E; Zamboni, M; Ferini-Strambi, L

    2001-03-01

    Depression is the most prevalent functional psychiatric disorder in late life. The problem of motor disorders associated with antidepressant use is relevant in the elderly. Elderly people are physically more frail and more likely to be suffering from physical illness, and any drug given may exacerbate pre-existing diseases, or interact with other drug treatments being administered for physical conditions. Antidepressants have been reported to induce extrapyramidal symptoms, including parkinsonism. These observations prompted us to review the neurobiological mechanism that may be involved in this complex interplay including neurotransmitters and neuronal circuits involved in movement and emotion control and their changes related to aging and disease. The study of the correlations between motor and mood disorders and their putative biochemical bases, as presented in this review, provide a rationale either to understand or to foresee motor side effects for psychotropic drugs, in particular antidepressants. PMID:11317214

  2. Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA

    NARCIS (Netherlands)

    Prieto-Alhambra, D.; Petri, H.; Goldenberg, J. S B; Khong, T. P.; Klungel, O. H.; Robinson, N. J.; De Vries, F.

    2014-01-01

    The association between antidepressant use and hip fracture remains unclear. We conducted a systematic review to estimate Population Attributable Risks (PAR) for France, Germany, Italy, Spain, UK, and the USA. We report a heterogeneous prevalence of antidepressant use and related PARs, both lowest f

  3. The antidepressant tianeptine persistently modulates glutamate receptor currents of the hippocampal CA3 commissural associational synapse in chronically stressed rats

    NARCIS (Netherlands)

    Kole, MHP; Swan, L; Fuchs, E

    2002-01-01

    Recent hypotheses on the action of antidepressants imply a modulation of excitatory amino acid transmission. Here, the effects of long-term antidepressant application in rats with the drug tianeptine were examined at hippocampal CA3 commissural associational (c/a) glutamate receptor ion channels, em

  4. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

    OpenAIRE

    Jia, Lin; Shang, Yuan-Yuan; Li, Yu-Yuan

    2008-01-01

    AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and selective serotonin reuptake inhibitor (SSRI) antidepressant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancreatic carcinoma xenografts in nude mice.

  5. The effect of knowledge and expectations on adherence to and persistence with antidepressants

    Directory of Open Access Journals (Sweden)

    Woodward SC

    2016-05-01

    Full Text Available Sophie Claire Woodward, Bonnie Jayne Bereznicki, Juanita Louise Westbury, Luke Ryan Elliot Bereznicki Pharmacy, School of Medicine, University of Tasmania, Hobart, TAS, Australia Purpose: Adherence to and persistence with antidepressants are often suboptimal. However, little is known about how patient knowledge and outcome expectations may influence antidepressant adherence and persistence.Method: Individuals who had been prescribed their first antidepressant to treat depression in the preceding 6 months were recruited to an online survey via Facebook. Knowledge, education received, and initial outcome expectations were analyzed for associations with persistence and adherence.Results: Two hundred and twenty surveys were analyzed. A total of 117 participants had taken their antidepressant for at least 3 months; another 25 had never started or stopped after <3 months without consulting their doctor. Differences in expectations and various educational messages among persistent and nonpersistent participants were identified. Having received the instruction “don’t stop it without checking with your doctor” was a significant independent predictor of persistence (odds ratio [OR] =5.9, 95% confidence interval [CI] =1.4–24.5. At the time of the survey, 82.7% of participants were taking an antidepressant and 77.9% were adherent. Significant independent predictors of adherence were a greater age (OR =1.1, 95% CI =1.0–1.2, knowledge (OR =1.6, 95% CI =1.1–2.3, being informed of common side effects (OR =5.5, 95% CI =1.1–29.0, and having discussed ways to solve problems (OR =3.9, 95% CI =1.1–14.5.Conclusion: Improving outcome expectations and particular educational messages may increase adherence and persistence. Greater knowledge may enhance adherence. Further investigation is warranted to determine whether a focus on these simple educational messages will improve outcomes in patients who commence an antidepressant.Keywords: counseling

  6. A genome-wide association study points to multiple loci predicting antidepressant treatment outcome in depression

    Science.gov (United States)

    Binder, Elisabeth B.; Bettecken, Thomas; Uhr, Manfred; Ripke, Stephan; Kohli, Martin A.; Hennings, Johannes M.; Horstmann, Sonja; Kloiber, Stefan; Menke, Andreas; Bondy, Brigitta; Rupprecht, Rainer; Domschke, Katharina; Baune, Bernhard T.; Arolt, Volker; Rush, A. John; Holsboer, Florian; Müller-Myhsok, Bertram

    2015-01-01

    Context Efficacy of antidepressant treatment in depression is unsatisfactory as one in three patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome. Objective To identify genetic and clinical determinants of antidepressant treatment outcome in depression. Design Genome-wide pharmacogenetic association study with two independent replication samples. Setting We performed a genome-wide association (GWA) study in patients from the Munich-Antidepressant-Response-Signature (MARS) project and in pooled DNA from an independent German replication sample. A set of 328 single nucleotide polymorphisms (SNPs) highly related to outcome in both GWA studies was genotyped in a sample of the Sequenced-Treatment-Alternatives-to-Relieve-Depression (STAR*D) study. Participants 339 inpatients suffering from a depressive episode (MARS sample), further 361 depressed inpatients (German replication sample), and 832 outpatients with major depression (STAR*D sample). Main Outcome Measures We generated a multi-locus genetic variable describing the individual number of alleles of the selected SNPs associated with beneficial treatment outcome in the MARS sample (“response” alleles) to evaluate additive genetic effects on antidepressant treatment outcome. Results Multi-locus analysis revealed a significant contribution of a binary variable categorizing patients as carriers of a high vs. low number of response alleles in predicting antidepressant treatment outcome in both samples, MARS and STAR*D. In addition, we observed that patients with a comorbid anxiety disorder in combination with a low number of response alleles showed the least favorable outcome. Conclusion Our results demonstrate the importance of multiple genetic factors in combination with clinical features to predict antidepressant treatment outcome underscoring the multifactorial nature of this trait. PMID

  7. Chronic stress and antidepressant induced changes in Hdac5 and Sirt2 affect synaptic plasticity.

    Science.gov (United States)

    Erburu, M; Muñoz-Cobo, I; Domínguez-Andrés, J; Beltran, E; Suzuki, T; Mai, A; Valente, S; Puerta, E; Tordera, R M

    2015-11-01

    Changes in histone acetylation could contribute to the pathogenesis of depression and antidepressant therapy. Using the chronic social defeat stress (CSDS) model of depression and different antidepressant treatments we studied the regulation of histone deacetylases (Hdac׳s) and synaptic plasticity markers in the prefrontal cortex (PFC). Further, functional implication of identified Hdac׳s in brain plasticity was explored. Mice were exposed to CSDS (10 days) followed by saline or imipramine (4 weeks). PFC Hdac׳s mRNA abundance was studied and compared to human׳s. Further, protein expression of acetylated histones (AcH3 and AcH4), neuroplasticity markers (CREB and pro-BDNF) and selected Hdac׳s were analyzed. Moreover, other antidepressants (fluoxetine and reboxetine) and selective HDAC inhibitors were studied. CSDS increased Hdac5 and Sirt2 mRNA whereas repeated imipramine did the opposite. Accordingly, stress and imipramine induced opposite changes on AcH3, AcH4 and CREB expression. At protein level, CSDS upregulated nuclear fraction of Hdac5 and repeated imipramine and reboxetine increased its phosphorylated form (p-Hdac5), mainly located in the cytoplasm. Moreover, Sirt2 was downregulated by all monoaminergic antidepressants. Further, repeated treatment with the class IIa Hdac inhibitor MC1568 and the Sirt2 inhibitor 33i for three weeks increased synaptic plasticity in the prefrontal cortex. Our results suggest that Hdac5 and Sirt2 upregulation could constitute stable stress-induced neuronal adaptations. Noteworthy, the SIRT2 upregulation in depressed patients supports the interest of this target for therapeutic intervention. On the other hand, cytoplasmic Hdac5 export and Sirt2 downregulation induced by monoaminergic antidepressants could contribute to the well-known beneficial effects of antidepressants on brain plasticity. PMID:26433268

  8. The effect of knowledge and expectations on adherence to and persistence with antidepressants

    Science.gov (United States)

    Woodward, Sophie Claire; Bereznicki, Bonnie Jayne; Westbury, Juanita Louise; Bereznicki, Luke Ryan Elliot

    2016-01-01

    Purpose Adherence to and persistence with antidepressants are often suboptimal. However, little is known about how patient knowledge and outcome expectations may influence antidepressant adherence and persistence. Method Individuals who had been prescribed their first antidepressant to treat depression in the preceding 6 months were recruited to an online survey via Facebook. Knowledge, education received, and initial outcome expectations were analyzed for associations with persistence and adherence. Results Two hundred and twenty surveys were analyzed. A total of 117 participants had taken their antidepressant for at least 3 months; another 25 had never started or stopped after <3 months without consulting their doctor. Differences in expectations and various educational messages among persistent and nonpersistent participants were identified. Having received the instruction “don’t stop it without checking with your doctor” was a significant independent predictor of persistence (odds ratio [OR] =5.9, 95% confidence interval [CI] =1.4–24.5). At the time of the survey, 82.7% of participants were taking an antidepressant and 77.9% were adherent. Significant independent predictors of adherence were a greater age (OR =1.1, 95% CI =1.0–1.2), knowledge (OR =1.6, 95% CI =1.1–2.3), being informed of common side effects (OR =5.5, 95% CI =1.1–29.0), and having discussed ways to solve problems (OR =3.9, 95% CI =1.1–14.5). Conclusion Improving outcome expectations and particular educational messages may increase adherence and persistence. Greater knowledge may enhance adherence. Further investigation is warranted to determine whether a focus on these simple educational messages will improve outcomes in patients who commence an antidepressant. PMID:27226710

  9. [Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder].

    Science.gov (United States)

    Tanaka, Teruaki; Inoue, Takeshi; Suzuki, Katsuji; Kitaichi, Yuji; Masui, Takuya; Denda, Kenzo; Koyama, Tsukasa

    2007-01-01

    Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to

  10. Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

    Science.gov (United States)

    Feltmann, Kristin; Konradsson-Geuken, Åsa; De Bundel, Dimitri; Lindskog, Maria; Schilström, Björn

    2015-12-01

    Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression. PMID:26501179

  11. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders;

    2010-01-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core ...... of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity....

  12. Prevalence and factors associated with off-label antidepressant prescriptions for insomnia

    Directory of Open Access Journals (Sweden)

    Lai L

    2011-07-01

    Full Text Available L Leanne Lai¹, Mooi Heong Tan¹, Yen Chi Lai²¹Department of Sociobehavioral and Administrative Pharmacy, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA; ²Department of Internal Medicine, Golen Hospital, Pintong City, TaiwanBackground: The primary objective of our study was to investigate the prevalence of off-label antidepressant drug use in insomnia. The secondary objective was to compare prescribing patterns between off-label antidepressants vs hypnotics approved by the US Food and Drug Administration for insomnia, with particular emphasis on socioeconomic characteristics of patients and physicians.Methods: We undertook a secondary data analysis using the national longitudinal database from the 2006 National Ambulatory Medical Care Survey. Subjects were identified from outpatient visits in which at least one insomnia drug was prescribed. A series of weighted Chi-squared statistics was used to compare drug use for insomnia across various patient and physician characteristics. Multivariate logistic regression was conducted to identify factors associated with off-label antidepressant drug use.Results: Among 901.95 million outpatient visits that took place in the US in 2006, an estimated 30.43 million visits included at least one drug prescription for insomnia. Off-label antidepressants were prescribed significantly more frequently (45.1% than nonbenzodiazepine z-hypnotics (43.2% and benzodiazepines (11.7%. Insomnia prescribing patterns were significantly influenced by physician specialty and physician office settings. Pediatricians (odds ratio [OR]: 65.892; 95% confidence interval [CI]: 5.536–810.564 and neurologists (OR: 4.784; 95% CI: 2.044–11.201 were more likely to prescribe off-label antidepressants than psychiatrists. Self-paying patients were more likely to receive off-label antidepressants as treatment for insomnia than patients with private insurance (OR 2.594; 95% CI: 1.128–5.967.Conclusion: Our

  13. Comparison of the antidepressant effects of venlafaxine and dosulepin in a naturalistic setting

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Jørgensen, Martin Balslev; Dam, Henrik;

    2009-01-01

    The relative efficacy of the various classes of antidepressants has not been established. Observational studies in naturalistic settings are important in evaluating treatment outcomes with antidepressants, since controlled clinical trials include only a minority of patients present in clinical...... practice. This study sought to evaluate in a naturalistic setting the treatment outcomes of dosulepin and venlafaxine for patients with depressive episodes. At the university hospital in Copenhagen, Denmark, between 1998 and early 2001, the first-line treatment for psychiatric inpatients with depression...... because of an underpowered design) after replacing dosulepin with venlafaxine as first-line drug for depression in a naturalistic inpatient setting....

  14. Antidepressant-like effects and mechanisms of flavonoids and related analogues.

    Science.gov (United States)

    Guan, Li-Ping; Liu, Bing-Yu

    2016-10-01

    Flavonoids, possessing a basic phenylbenzopyrone core, are important components of the human diet, and are found in many medicinal plants. Flavonoids include chalcones, flavanones and their derivatives. Synthetic and natural isolated flavonoids display an enormous number of biological activities such as antitumor, antiplatelet, anti-malarial, anti-inflammatory, antidepressant and anticonvulsant properties. This review article focuses on the antidepressant-like effect, structure-activity relationship and mechanism of action of total flavonoid extracts isolation from natural sources, flavonoid compounds and their related analogues. PMID:27214511

  15. 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

    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...... obvious need of intensive care. Of the 157 patients included, 12 patients (8%) developed events during the ICU stay. Only 3 patients received intubation, vasoactive drugs and/or dialysis. None developed ventricular dysrhythmias. There were no fatalities. All the patients with low-risk assessment by ADORA...

  16. Selective serotonin reuptake inhibitor (SSRI antidepressants, prolactin and breast cancer

    Directory of Open Access Journals (Sweden)

    Janet eAshbury

    2012-12-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are a widely prescribed class of anti-depressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003-2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with nonusers of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively, regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40 for long-term users of sertraline (≥24 prescriptions, given the small number of exposed cases (n=12, the borderline statistical significance and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.

  17. Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression.

    Science.gov (United States)

    Vai, Benedetta; Poletti, Sara; Radaelli, Daniele; Dallaspezia, Sara; Bulgarelli, Chiara; Locatelli, Clara; Bollettini, Irene; Falini, Andrea; Colombo, Cristina; Smeraldi, Enrico; Benedetti, Francesco

    2015-08-30

    The identification of antidepressant response predictors in bipolar disorder (BD) may provide new potential enhancements in treatment selection. Repeated total sleep deprivation combined with light therapy (TSD+LT) can acutely reverse depressive symptoms and has been proposed as a model antidepressant treatment. This study aims at investigating the effect of TSD+LT on effective connectivity and neural response in cortico-limbic circuitries during implicit processing of fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling (DCM) were combined to study the effect of chronotherapeutics on neural responses in healthy controls (HC, n = 35) and BD patients either responder (RBD, n = 26) or non responder (nRBD, n = 11) to 3 consecutive TSD+LT sessions. Twenty-four DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were constructed. After treatment, patients significantly increased their neural responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint neural responses than RBD. The increased activity in ACC and in medial prefrontal cortex, associated with antidepressant treatment, was positively associated with the improvement of depressive symptomatology. Only RBD patients increased intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the task on Amy-DLPFC connection. A successful antidepressant treatment was associated with an increased functional activity and connectivity within cortico-limbic networks, suggesting the possible role of these measures in providing possible biomarkers for treatment efficacy. PMID:26195295

  18. Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice

    Directory of Open Access Journals (Sweden)

    Vanzella Cláudia

    2012-04-01

    Full Text Available Abstract Background Hibiscus tiliaceus L. (Malvaceae is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. Methods Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. Results Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. Conclusion Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect.

  19. Do Antidepressant Advertisements Educate Consumers and Promote Communication Between Patients with Depression and Their Physicians?

    Science.gov (United States)

    Bell, Robert A.; Taylor, Laramie D.; Kravitz, Richard L.

    2010-01-01

    Objective To examine how online depression support group members respond to direct-to-consumer (DTC) antidepressant advertising. Methods Survey of 148 depression forum members, administered via an online questionnaire. Results Chronicity was high, as 79.1% had received a diagnosis of depression 3 or more years earlier. Respondents reported seeing advertisements for an average of 4.3 of 7 brands investigated. A majority rated the information quality of these advertisements as “poor” or “fair.” Attitudes toward antidepressant advertisements were neutral (mean: 2.96 on a 5-point scale). More than half (52.4%) visited official websites provided in these advertisements, 39.9% had talked with a doctor after seeing an advertisement, 20.3% made an advertisement-induced prescription request, and 25.7% said these advertisements reminded them to take their antidepressants. Amount of attention given to these advertisements correlated positively with belief in the brain chemical imbalance causal model, but belief in this model did not predict prescription requests. Conclusion Awareness of DTC antidepressant advertisements is high among individuals with depression, but so is skepticism. Practice Implications Among members of an on-line support group, these advertisements encourage patient-doctor dialogue, prescription requests, and adherence, but might also reduce the acceptability of psychotherapy and encourage doctor switching in a small number of patients. PMID:20176456

  20. Does good leadership buffer effects of high emotional demands at work on risk of antidepressant treatment?

    DEFF Research Database (Denmark)

    Madsen, Ida E H; Hanson, Linda L Magnusson; Rugulies, Reiner Ernst; Theorell, Töres; Burr, Hermann; Diderichsen, Finn; Westerlund, Hugo

    2014-01-01

    Emotionally demanding work has been associated with increased risk of common mental disorders. Because emotional demands may not be preventable in certain occupations, the identification of workplace factors that can modify this association is vital. This article examines whether effects of...... emotional demands on antidepressant treatment, as an indicator of common mental disorders, are buffered by good leadership....

  1. Evaluation of anti-depressant effect of lemon grass (Cymbopogon citratus in albino mice

    Directory of Open Access Journals (Sweden)

    Sujata Dudhgaonkar

    2014-08-01

    Results: Lemon grass at the above doses significantly reduced the immobility time in both the tests compared with the control (C. citratus has significant anti-depressant activity comparable to imipramine. [Int J Basic Clin Pharmacol 2014; 3(4.000: 656-660

  2. Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

    Science.gov (United States)

    Osborn, Meagan; Rustom, Nazneen; Clarke, Melanie; Litteljohn, Darcy; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

    2013-01-01

    Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity. PMID:24019878

  3. Effect of lipopolysaccharide and antidepressant drugs on glucocorticoid receptor-mediated gene transcription

    Czech Academy of Sciences Publication Activity Database

    Budziszewska, B.; Basta-Kaim, A.; Kubera, M.; Jaworska, L.; Leskiewicz, M.; Tetich, M.; Otczyk, M.; Zajícová, Alena; Holáň, Vladimír; Lasoń, W.

    2005-01-01

    Roč. 57, č. 4 (2005), s. 540-544. ISSN 1734-1140 Grant ostatní: State Committee for Scientific Research (KBN)(PL) 6P05A076 Institutional research plan: CEZ:AV0Z5052915 Keywords : glucocorticoid receptor * antidepressant drugs * interleukin-6 Subject RIV: EB - Genetics ; Molecular Biology

  4. Mixed-effects Poisson regression analysis of adverse event reports: the relationship between antidepressants and suicide.

    Science.gov (United States)

    Gibbons, Robert D; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K; Bhaumik, Dulal K; Brown, C Hendricks; Kapur, Kush; Marcus, Sue M; Hur, Kwan; Mann, J John

    2008-05-20

    A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  5. Binding of the Multimodal Antidepressant Drug Vortioxetine to the Human Serotonin Transporter

    DEFF Research Database (Denmark)

    Andersen, Jacob; Ladefoged, Lucy Kate; Wang, Danyang;

    2015-01-01

    Selective inhibitors of the human serotonin transporter (hSERT) have been first-line treatment against depression for several decades. Recently, vortioxetine was approved as a new therapeutic option for the treatment of depression. Vortioxetine represents a new class of antidepressant drugs...

  6. Relationship between antidepressant effect and plasma level of nortriptyline. Clinical studies.

    Science.gov (United States)

    Kragh-Søorensen, P; Hansen, C E; Baastrup, P C

    1976-01-01

    Strong evidence has been found for the assumption that NT inhibits its own antidepressive effect at high, but non toxic plasma levels in patients suffering from endogenous depression. Based on three investigations we will recommend an optimal therapeutic plasma range for NT between 50 and 150 ng NT/ml. PMID:790409

  7. Prescribing pattern of antidepressants in psychiatric unit of a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    E. Avanthi

    2014-08-01

    Conclusions: Depression is more commonly seen in married people predominantly in females and housewives. Fluoxetine is more commonly used followed by escitalopram. Selective serotonin reuptake inhibitors are preferred over other antidepressant because of their relative lesser side effects. [Int J Basic Clin Pharmacol 2014; 3(4.000: 667-670

  8. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants.

    Science.gov (United States)

    Duman, Ronald S; Aghajanian, George K; Sanacora, Gerard; Krystal, John H

    2016-03-01

    Depression is a common, devastating illness. Current pharmacotherapies help many patients, but high rates of a partial response or no response, and the delayed onset of the effects of antidepressant therapies, leave many patients inadequately treated. However, new insights into the neurobiology of stress and human mood disorders have shed light on mechanisms underlying the vulnerability of individuals to depression and have pointed to novel antidepressants. Environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology, resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function. Although current antidepressants, such as serotonin-reuptake inhibitors, produce subtle changes that take effect in weeks or months, it has recently been shown that treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants. Within a similar time scale, these new agents have also been shown to reverse the synaptic deficits caused by stress. PMID:26937618

  9. Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Holubová, Kristina; Kletečková, Lenka; Škurlová, Martina; Říčný, J.; Stuchlík, Aleš; Valeš, Karel

    2016-01-01

    Roč. 233, č. 11 (2016), s. 2077-2097. ISSN 0033-3158 R&D Projects: GA MZd(CZ) NT13403 Institutional support: RVO:67985823 Keywords : ketamine * rapamycin * antidepressants * anxiety * cognitive deficit * bulbectomy * mTOR * BDNF Subject RIV: FH - Neurology Impact factor: 3.875, year: 2014

  10. Regioselective synthesis and evaluation of 3-alkylidene-1, 3-dihydroisobenzofurans as potential antidepressant agents

    Indian Academy of Sciences (India)

    C Praveen; C Iyyappan; K Girija; K Suresh Kumar; P T Perumal

    2012-03-01

    3-Alkylidene-1,3-dihydroisobenzofurans exhibited moderate antidepressant activity as evaluated by forced swim and tail suspension test methods. Virtual screening was carried out by docking the designed compounds into the serotonin binding sites of arabinase protein to predict the analogue binding mode of the compounds to the SSRIs.

  11. Antidepressant Drugs for Chronic Urological Pelvic Pain: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Christos Papandreou

    2009-01-01

    Full Text Available The use of antidepressant drugs for the management of chronic pelvic pain has been supported in the past. This study aimed to evaluate the available evidence for the efficacy and acceptability of antidepressant drugs in the management of urological chronic pelvic pain. Studies were selected through a comprehensive literature search. We included all types of study designs due to the limited evidence. Studies were classified into levels of evidence according to their design. Ten studies were included with a total of 360 patients. Amitriptyline, sertraline, duloxetine, nortriptyline, and citalopram are the antidepressants that have been reported in the literature. Only four randomized controlled trials (RCTs were identified (two for amitriptyline and two for sertraline with mixed results. We conclude that the use of antidepressants for the management of chronic urological pelvic pain is not adequately supported by methodologically sound RCTs. From the existing studies amitriptyline may be effective in interstitial cystitis but publication bias should be considered as an alternative explanation. All drugs were generally well tolerated with no serious events reported.

  12. Potential antidepressant properties of cysteamine on hippocampal BDNF levels and behavioral despair in mice.

    Science.gov (United States)

    Shieh, Chu-Hsin; Hong, Chen-Jee; Huang, Yn-Ho; Tsai, Shih-Jen

    2008-08-01

    Several studies have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels, suggesting that BDNF signaling is important for the therapeutic mechanism of antidepressants. Recent work has found that cysteamine and its related agent, cystamine, are neuroprotective in Huntington's disease mice, and act by enhancing the secretion of central BDNF. In the present study, the potential antidepressant effects of cysteamine were examined by behavioral paradigms and biochemical assay. Male BALB/CByJ mice were given a single dose of normal saline, 10 mg/kg of imipramine or either 50, 100 or 200 mg/kg of cysteamine (i.p.) 30 min before undergoing the forced-swimming test (FST) or the tail suspension test (TST). Other groups of mice treated with the same drugs and doses, without behavioral tests, were sacrificed for hippocampal BDNF measurements. We found that, compared with the control group, the cysteamine 200-mg/kg group showed a significant reduction in immobility time in the FST (Pcysteamine 200-mg/kg group (Pcysteamine may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels. PMID:18582526

  13. Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andres; Bloch, Michael H.

    2011-01-01

    Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main…

  14. Review of the Efficacy and Safety of Antidepressants in Youth Depression

    Science.gov (United States)

    Cheung, Amy H.; Emslie, Graham J.; Mayes, Taryn L.

    2005-01-01

    Background: Depression in children and adolescents is a cause of substantial morbidity and mortality in this population. It is a common disorder that affects 2% of children and up to 6% of adolescents. Although antidepressants are used frequently for the treatment of this disorder, there has been recent controversy about the efficacy and safety of…

  15. Using tests and models to assess antidepressant-like activity in rodents

    Directory of Open Access Journals (Sweden)

    Kedzierska Ewa

    2016-06-01

    Full Text Available In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.

  16. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

  17. Antidepressant- like effects of BCEF0083 in the chronic unpredictable stress models

    Institute of Scientific and Technical Information of China (English)

    LanlanZhou; LiangMING; ChuangengMa; YanCheng; QinJiang

    2004-01-01

    AIM: Depression is a complicated disease, There are no satisfactory drugs to therapy depression so far. BCEF is a new type of bioactive compounds from entomogenous fungi. Depression animal models are effective to evaluate the antidepressant property of drugs. Several animal models of depression have been inn'oduced, however, only a few have been

  18. Relationship of Prior Antidepressant Exposure to Long-Term Prospective Outcome in Bipolar I Disorder Outpatients

    NARCIS (Netherlands)

    Post, Robert M.; Leverich, Gabriele S.; Altshuler, Lori L.; Frye, Mark A.; Suppes, Trisha; McElroy, Susan L.; Keck, Paul E.; Nolen, Willem A.; Rowe, Mike; Kupka, Ralph W.; Grunze, Heinz; Goodwin, Frederick K.

    2012-01-01

    Objective:The long-term impact of prior antidepressant exposure on the subsequent course of bipolar illness remains controversial. Method: 139 outpatients (mean age, 42 years) with bipolar I disorder diagnosed by DSM-IV criteria had a detailed retrospective examination of their prior course of illne

  19. Antidepressant effect of bioactive compounds from Paecilomyces tenuipes in mice and rats

    Institute of Scientific and Technical Information of China (English)

    Hongwei Kan; Liang Ming; Chunru Li; Hongxing Kan; Bei Sun; Yan Liang

    2010-01-01

    A bioactive compound from Paecilomyces tenuipes(BCPT)has an inhibitory effect on monoamine oxidase A(MAO-A)in vitro.Researchers have thought that BCPT may be a potential antidepressant.The MAO-A suppressor moclobemide served as a control,and this study investigated the mechanisms of BCPT as an antidepressant.Results demonstrated that BCPT induced significantly increased sucrose intake in chronic unpredictable stressed rats,shortened immobility time in forced swimming mice,improved the scores of blepharoptosis and akinesia in reserpine-treated mice,increased the number of 5-hydroxy tryptophan-induced head-twitches,remarkably enhanced the expression of hippocampus mineralcorticoid receptor and glucocorticoid receptor mRNA,decreased the ratio of mineralcorticoid receptor to glucocorticoid receptor and raised the levels of dopamine,norepinephrine and 5-hydroxytryptamine,while decreasing hydroxyindole acetic acid levels or dihydroxy-phenyl acetic acid in chronic unpredictable stressed rats.Behavioral test results suggested that BCPT potentially had antidepressant-like activity.Meanwhile,BCPT increased the levels of neurotransmitters,and mineralcorticoid receptor and glucocorticoid receptor mRNA in the hippocampus,which may be an important mechanism of its antidepressant effect.

  20. Antidepressant-like Effect of Insulin in Streptozotocin-induced Type 2 Diabetes Mellitus Rats.

    Science.gov (United States)

    Sestile, Caio C; Maraschin, Jhonatan C; Rangel, Marcel P; Cuman, Roberto K N; Audi, Elisabeth A

    2016-09-01

    This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM. PMID:26857652

  1. Antidepressant and neurocognitive effects of isoflurane anesthesia versus electroconvulsive therapy in refractory depression.

    Directory of Open Access Journals (Sweden)

    Howard R Weeks

    Full Text Available BACKGROUND: Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT. Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. METHOD: Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20 or isoflurane (n = 8 over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24 and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency were assessed at Pretreatment, Post all treatments and 4-week Follow-up. RESULTS: Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. CONCLUSIONS: Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.

  2. Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    A. Etiévant

    2015-08-01

    Full Text Available Although deep brain stimulation (DBS shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K+ buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz DBS. It is proposed that an unaltered neuronal–glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

  3. The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants.

    Science.gov (United States)

    Köhler, Stephan; Cierpinsky, Katharina; Kronenberg, Golo; Adli, Mazda

    2016-01-01

    The monoamine hypothesis of depression posits that an imbalance in monoaminergic neurotransmission is causally related to the clinical features of depression. Antidepressants influencing serotonin mainly aim at raising serotonin concentrations, thereby increasing serotonergic transmission at the level of the synapse, for example by inhibiting the serotonin transporter. However, the serotonin system is multifaceted. Different serotonin receptor subtypes turn the serotonergic system into a complex neurochemical arrangement that influences diverse neurotransmitters in various brain regions. Classical antidepressants as well as other psychopharmacological agents have various crucial effects on serotonin receptors. We aim at providing a clinically useful characterization of serotonin receptor subtypes in the treatment of depression. Clarifying the mode of action and the interplay of serotonin receptors with pharmacological agents should help antidepressant mechanisms and typical side effects to be better understood. Against this background, we feature the novel antidepressants vortioxetine, vilazodone and milnacipran/levomilnacipran with regard to their serotonin receptor targets such as the 5-HT1A, 5-HT3 and 5-HT7 which may account for their specific effects on certain symptoms of depression (e.g. cognition and anxiety) as well as a characteristic side-effect profile. PMID:26464458

  4. Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use

    NARCIS (Netherlands)

    Dortland, A. K. B. van Reedt; Giltay, E. J.; van Veen, T.; Zitman, F. G.; Penninx, B. W. J. H.

    2010-01-01

    Objective: The metabolic syndrome (MetSyn) predisposes to cardiovascular disease and diabetes mellitus. There might also be an association between the MetSyn and anxiety and depression, but its nature is unclear. We aimed to investigate whether diagnosis, symptom severity and antidepressant use are

  5. Prevalence of depression, quality of life and antidepressant treatment in the Danish General Suburban Population Study

    DEFF Research Database (Denmark)

    Ellervik, Christina; Kvetny, Jan; Christensen, Kaj Sparle;

    2014-01-01

    describe the prevalence of antidepressants received by the respondents in the GESUS study and the correspondence to their subjective well-being on the WHO-5 questionnaire. METHODS: To evaluate the validity (scalability) of the MDI and the WHO-5 in the GESUS study we performed the non-parametric Mokken...

  6. N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.

    Science.gov (United States)

    Lin, Jen-Cheng; Chan, Ming-Huan; Lee, Mei-Yi; Chen, Yi-Chyan; Chen, Hwei-Hsien

    2016-11-01

    Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine. The present study determined the effects of DMG on the ketamine-induced psychotomimetic, anesthetic and antidepressant-like effects in mice. DMG pretreatment reversed the ketamine-induced locomotor hyperactivity and impairment in the rotarod performance, novel location and novel object recognition tests, and prepulse inhibition. In addition, DMG alone exhibited antidepressant-like effects in the forced swim test and produced additive effects when combined with ketamine. However, DMG did not affect ketamine-induced anesthesia. These results reveal that DMG could antagonize ketamine's psychotomimetic effects, yet produce additive antidepressant-like effects with ketamine, suggesting that DMG might have antipsychotic potential and be suitable as an add-on therapy to ketamine for patients with treatment-resistant depression. PMID:27296677

  7. Antidepressant-like effect of agmatine is not mediated by serotonin

    DEFF Research Database (Denmark)

    Krass, Maarja; Wegener, Gregers; Vasar, Eero;

    2008-01-01

    The aim of this study was to characterize the behavioral effects of systemically administered agmatine in animal models predictive of antidepressant- and anxiolytic-like activity and clarify whether the effects of agmatine depend on the intact serotonergic system. Only the highest dose of agmatin...

  8. Longitudinal Evidence for Unfavorable Effects of Antidepressants on Heart Rate Variability

    NARCIS (Netherlands)

    Licht, Carmilla M. M.; de Geus, Eco J. C.; van Dyck, Richard; Penninx, Brenda W. J. H.

    2010-01-01

    Background: It was previously shown that antidepressants are associated with diminished vagal control over the heart. Longitudinal studies are needed to test the causality of this association further. Methods: Longitudinal data were obtained in the Netherlands Study of Depression and Anxiety. At bas

  9. 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; Koldsø, Heidi; Schiøtt, Birgit; Strømgaard, Kristian; Kristensen, Anders S

    2014-01-01

    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...

  10. Pharmaceutical Citizenship: Antidepressant Marketing and the Promise of Demarginalization in India.

    Science.gov (United States)

    Ecks, Stefan

    2005-12-01

    Among practitioners of biomedicine, to speak of people as 'marginalized' often amounts to saying that they do not have access to medical substances. Thus conceived, the best way to remove marginality seems to be to give medicines to those deprived of them. The peculiar relationship between marginality and pharmaceuticals is especially poignant in the case of antidepressant drugs, as these drugs appear to bring the patient 'back into society', but not any society, but middle-class consumer society. What is now special about antidepressants is that there is nothing special about them: antidepressants are like consumer items among thousands of other consumer items. This paper explores the relations between medicines and marginality with reference to the marketing of antidepressant drugs in Kolkata (Calcutta), India. Drawing on ethnographic fieldwork in the Kolkata metropolitan area from July 1999 to December 2000 and in August/September 2003, this paper examines how people with depression are constituted as 'marginal' in the sense of 'being deprived of medication', and how the biomedical promise of an effective pharmacological treatment becomes a promise of 'pharmaceutical citizenship'. In view of Bengali notions of mental health as a state of detachment, the paper asks if pharmacological demarginalization holds the same promise in the Indian context that it holds in the West. PMID:26873669

  11. Síndrome de discontinuación de antidepresivos Withdrawal Syndrome of Antidepressants

    Directory of Open Access Journals (Sweden)

    Sandra Baeza

    2002-01-01

    Full Text Available Considerando el amplio uso de los antidepresivos evaluamos la existencia y características del síndrome de discontinuación de antidepresivos. Método. Usando MEDLINE identificamos reportes y artículos de revisión relevantes acerca de síntomas secundarios al retiro de antidepresivos. Resultados. Existe amplia evidencia acerca de un síndrome de discontinuación tras el retiro de antidepresivos tricíclicos, inhibidores de la monoaminooxidasa e inhibidores de recaptura de serotonina, habiéndose descrito desde molestias leves a cuadros severos con síntomas psicóticos y agitación, siendo en general más graves los síntomas asociados a discontinuación de inhibidores de la monoamino-oxidasa y tricíclicos. Conclusiones. La información obtenida debe ser considerada por los clínicos al momento de prescribir el inicio o retiro de antidepresivos. Debe tenerse en cuenta el síndrome de discontinuación de antidepresivos en pacientes que presentan bruscas exacerbaciones sintomáticas. Se sugiere como medida preventiva la disminución gradual de las dosis antes de suspender un antidepresivoIntroduction. Antidepressants have been used widely without take in account the potential risks of the discontinuation process. Even more, a lot of physicians do not know the characteristics of this syndrome. Methods. Using MEDLINE we identified review papers and reports about antidepressants withdrawal symptoms. Results. We found wide evidence about an antidepressant withdrawal syndrome associated with tricyclics antidepressants, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors. It could be mild but sometimes it is severe, with agitation and psychotic symptoms inclusive. The most severe withdrawal symptoms tends to occur using tricyclics antidepressants and monoamine oxidase inhibitors. Conclusion. This information must be considered when clinicians decide to begin or to suppress an antidepressant treatment, and specially when there

  12. 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

  13. Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS

    Science.gov (United States)

    Schultz, M.M.; Furlong, E.T.

    2008-01-01

    Treated wastewater effluent is a potential environmental point source for antidepressant pharmaceuticals. A quantitative method was developed for the determination of trace levels of antidepressants in environmental aquatic matrixes using solid-phase extraction coupled with liquid chromatography- electrospray ionization tandem mass spectrometry. Recoveries of parent antidepressants from matrix spiking experiments for the individual antidepressants ranged from 72 to 118% at low concentrations (0.5 ng/L) and 70 to 118% at high concentrations (100 ng/L) for the solid-phase extraction method. Method detection limits for the individual antidepressant compounds ranged from 0.19 to 0.45 ng/L. The method was applied to wastewater effluent and samples collected from a wastewater-dominated stream. Venlafaxine was the predominant antidepressant observed in wastewater and river water samples. Individual antidepressant concentrations found in the wastewater effluent ranged from 3 (duloxetine) to 2190 ng/L (venlafaxine), whereas individual concentrations in the waste-dominated stream ranged from 0.72 (norfluoxetine) to 1310 ng/L (venlafaxine). ?? 2008 American Chemical Society.

  14. Evaluating antidepressant treatment prior to adding second-line therapies among patients with treatment-resistant depression.

    Science.gov (United States)

    Hassan, Amany K; Farmer, Kevin C; Brahm, Nancy C; Neas, Barbara R

    2016-04-01

    Background Patients with depression can be mistakenly labeled as treatment-resistant if they fail to receive an adequate first-line antidepressant trial. Adding second-line agents to the treatment regimens can create an additional burden on both the patients and the healthcare system. Objectives To determine if depressed patients receive an adequate antidepressant trial prior to starting second-line therapy and to investigate the association between the type of second-line treatment and severity of illness or depression among unipolar versus bipolar patients. Setting Oklahoma Medicaid claims data between 2006 and 2011. Methods Subjects were depression-diagnosed adult patients with at least two prescriptions of antidepressants followed by a second-line agent. Patients were categorized into one of three groups: an atypical antipsychotic, other augmentation agents (lithium, buspirone, and triiodothyronine), or adding antidepressants, based on the type of second-line therapy. An adequate trial was defined per the American Psychiatric Association guidelines. Factors associated with the type of treatment were tested using multinomial logistic regression models stratified by type of depression (unipolar vs. bipolar patients). Main outcome measure Variables used to measure receiving an adequate antidepressant trial included: trial duration, adherence, dose adequacy, and number of distinct antidepressant trials. Results A total of 3910 patients were included in the analysis. Most subjects reached the recommended antidepressant dose. However, 28 % of patients had an antidepressant trial duration depression. These findings support policies that require reviewing the recommended dose and duration of the first-line antidepressant before adding second-line agents. Healthcare providers need to review the patient's history and reconsider the evidence for prescribing second-line agents. PMID:26935957

  15. Long-Term Weight Change after Initiating Second-Generation Antidepressants.

    Science.gov (United States)

    Arterburn, David; Sofer, Tamar; Boudreau, Denise M; Bogart, Andy; Westbrook, Emily O; Theis, Mary Kay; Simon, Greg; Haneuse, Sebastien

    2016-01-01

    (1) OBJECTIVE: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2) METHODS: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3) RESULTS: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: -11.3, -2.8; p-value bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: -2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02); (4) CONCLUSION: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications. PMID:27089374

  16. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk.

    Science.gov (United States)

    Borg, Linda; Julkunen, Anna; Rørbaek Madsen, Kristian; Strøm, Thomas; Toft, Palle

    2016-07-01

    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 intensive care treatment. This retrospective study was conducted in adult patients admitted to the ICU at Odense University Hospital after an overdose with AP and/or AD between 1 January 2009 and 1 September 2014. Patients with predefined adverse signs in the emergency department were excluded due to obvious need of intensive care. Of the 157 patients included, 12 patients (8%) developed events during the ICU stay. Only 3 patients received intubation, vasoactive drugs and/or dialysis. None developed ventricular dysrhythmias. There were no fatalities. All the patients with low-risk assessment by ADORA within the first 6 hr did not develop events within the first 24 hr after hospital admission. The vast majority of patients with AD and/or AP overdose and no adverse signs at admission did not require intensive care treatment. Low-risk ADORA identified patients with antidepressant as well 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. PMID:26663682

  17. Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

    Science.gov (United States)

    Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit

    2016-01-01

    Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy. PMID:26555033

  18. In vivo studies of effects of antidepressants on parotid salivary secretion in the rat.

    Science.gov (United States)

    Johnsson, Martin; Winder, Michael; Zawia, Hana; Lödöen, Ida; Tobin, Gunnar; Götrick, Bengt

    2016-07-01

    Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (-40 to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and β-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia. PMID:27023402

  19. Neonatal adaptation in infants prenatally exposed to antidepressants--clinical monitoring using Neonatal Abstinence Score.

    Directory of Open Access Journals (Sweden)

    Lisa Forsberg

    Full Text Available BACKGROUND: Intrauterine exposure to antidepressants may lead to neonatal symptoms from the central nervous system, respiratory system and gastrointestinal system. Finnegan score (Neonatal Abstinence Score, NAS has routinely been used to assess infants exposed to antidepressants in utero. AIM: The purpose was to study neonatal maladaptation syndrome in infants exposed to selective serotonin reuptake inhibitors (SSRI or serotonin-norepinephrine reuptake inhibitors (SNRI in utero. METHOD: Retrospective cohort study of women using antidepressants during pregnancy and their infants. Patients were identified from the electronic health record system at Karolinska University Hospital Huddinge containing pre-, peri- and postnatal information. Information was collected on maternal and infant health, social factors and pregnancy. NAS sheets were scrutinized. RESULTS: 220 women with reported 3rd trimester exposure to SSRIs or SNRIs and who gave birth between January 2007 and June 2009 were included. Seventy seven women (35% used citalopram, 76 used (35% sertraline, 34 (15% fluoxetine and 33 (15% other SSRI/SNRI. Twenty-nine infants (13% were admitted to the neonatal ward, 19 were born prematurely. NAS was analyzed in 205 patients. Severe abstinence was defined as eight points or higher on at least two occasions (on a scale with maximum 40 points, mild abstinence as 4 points or higher on at least two occasions. Seven infants expressed signs of severe abstinence and 46 (22% had mild abstinence symptoms. Hypoglycemia (plasma glucose <2.6 mmol/L was found in 42 infants (19%. CONCLUSION: Severe abstinence in infants prenatally exposed to antidepressants was found to be rare (3% in this study population, a slightly lower prevalence than reported in previous studies. Neonatal hypoglycemia in infants prenatally exposed to antidepressant may however be more common than previously described.

  20. Antidepressants reduce extinction-induced withdrawal and biting behaviors: a model for depressive-like behavior.

    Science.gov (United States)

    Huston, J P; van den Brink, J; Komorowski, M; Huq, Y; Topic, B

    2012-05-17

    The withholding of expected rewards results in extinction of behavior and, hypothetically, to depression-like symptoms. In a test of this hypothesis, we examined the effects of extinction of food-reinforced lever-pressing on collateral behaviors that might be indices of depression. Operant extinction is known to be aversive to the organism and results in avoidance behavior. We hypothesized that avoidance of, or withdrawal from, the former source of reward may serve as a marker for "despair." Adult male Wistar rats (n=6-7 animals per group) were exposed to a Skinner box attached to a second compartment of the same size, providing opportunity for the animals to leave the operant chamber and to enter the "withdrawal" compartment. The animals spent a portion of the time during the extinction trials in this second chamber. To assess the predictive validity of this behavior as a potential marker of "despair," we tested the effects of chronic administration of two common antidepressant drugs on this measure. The tricyclic antidepressant imipramine (20 mg/kg) as well as the selective serotonin reuptake inhibitor citalopram (20 mg/kg) reduced the number of entries and time spent in the withdrawal compartment. We propose that entries into and time spent in the withdrawal compartment may operationalize "avoidance," a core symptom of major depression. Rearing as well as biting behaviors during the extinction trials were also attenuated by the antidepressant treatment. These results lend support to the hypothesis that extinction of positively reinforced operants evokes behaviors that reflect elements of "despair/depression" because these behaviors are modulated by antidepressant treatment. The avoidance of the operant chamber as a consequence of extinction, together with rearing and biting behaviors, may serve as useful measures for the testing of antidepressant treatments. PMID:22410342

  1. Long-Term Weight Change after Initiating Second-Generation Antidepressants

    Directory of Open Access Journals (Sweden)

    David Arterburn

    2016-04-01

    Full Text Available (1 Objective: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2 Methods: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3 Results: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: −11.3, −2.8; p-value < 0.01; smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: −2.3, 6.8; p-value = 0.33. Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02; (4 Conclusion: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications.

  2. Inhibition of G protein-activated inwardly rectifying K+ channels by different classes of antidepressants.

    Directory of Open Access Journals (Sweden)

    Toru Kobayashi

    Full Text Available Various antidepressants are commonly used for the treatment of depression and several other neuropsychiatric disorders. In addition to their primary effects on serotonergic or noradrenergic neurotransmitter systems, antidepressants have been shown to interact with several receptors and ion channels. However, the molecular mechanisms that underlie the effects of antidepressants have not yet been sufficiently clarified. G protein-activated inwardly rectifying K(+ (GIRK, Kir3 channels play an important role in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to have therapeutic potential for several neuropsychiatric disorders and cardiac arrhythmias. In the present study, we investigated the effects of various classes of antidepressants on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2 or GIRK1/GIRK4 subunits, extracellular application of sertraline, duloxetine, and amoxapine effectively reduced GIRK currents, whereas nefazodone, venlafaxine, mianserin, and mirtazapine weakly inhibited GIRK currents even at toxic levels. The inhibitory effects were concentration-dependent, with various degrees of potency and effectiveness. Furthermore, the effects of sertraline were voltage-independent and time-independent during each voltage pulse, whereas the effects of duloxetine were voltage-dependent with weaker inhibition with negative membrane potentials and time-dependent with a gradual decrease in each voltage pulse. However, Kir2.1 channels were insensitive to all of the drugs. Moreover, the GIRK currents induced by ethanol were inhibited by sertraline but not by intracellularly applied sertraline. The present results suggest that GIRK channel inhibition may reveal a novel characteristic of the commonly used antidepressants, particularly sertraline, and contributes to some of the therapeutic effects and adverse effects.

  3. Antidepressant-like effect of Tagetes lucida Cav. extract in rats: involvement of the serotonergic system.

    Science.gov (United States)

    Gabriela, Guadarrama-Cruz; Javier, Alarcón-Aguilar Francisco; Elisa, Vega-Avila; Gonzalo, Vázquez-Palacios; Herlinda, Bonilla-Jaime

    2012-01-01

    It has been demonstrated that the decoction of the aerial parts of Tagetes lucida Cav. produces an antidepressant effect during the forced swimming test (FST) in rats. The aim of this study was to evaluate the effect of different organic extracts and one aqueous extract of the aerial parts of T. lucida on the FST. In addition, the possible involvement of the serotonergic system in the antidepressant-like effect of T. lucida in the FST was evaluated, as was its potential toxicological effect. The different extracts of T. lucida (methanol, hexane, dichloromethane and aqueous, 10 and 50 mg/kg), as well as fluoxetine (FLX, 5 mg/kg), were administered per os (p.o.) to rats for 14 days. All animals were subjected to the FST. Only the aqueous extract of T. lucida at a dose of 50 mg/kg significantly reduced immobility behavior and increased swimming in the FST, similar to FLX. Later, the aqueous extract of T. lucida (50mg/kg) was administered for 1, 7 and 14 days. An antidepressant effect was observed after 7 days of treatment. To evaluate the participation of the serotoninergic system, the animals were pretreated with PCPA, an inhibitor of serotonin synthesis (100 mg/kg/day for 4 consecutive days). The animals were treated with the aqueous extract of T. lucida (50 mg/kg) and FLX (5 mg/kg) 24 h after the final injection and were then subjected to the FST. Pretreatment with PCPA inhibited the antidepressant effect of both T. lucida and FLX. Finally, T. lucida was administered p.o. and intraperitoneal route to evaluate its acute toxicological effect. The aqueous extract of T. lucida, administered p.o., did not produce lethality or any significant changes in behavior. In conclusion, the aqueous extract of T. lucida manifested an antidepressant-like effect in the FST mediated by the serotonergic system, with no adverse effects when administered p.o. PMID:22809029

  4. Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lan-lan; MING Liang; MA Chuan-geng; CHENG Yan; JIANG Qin

    2005-01-01

    Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

  5. 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

  6. Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains.

    Science.gov (United States)

    Eisensamer, Brigitte; Uhr, Manfred; Meyr, Sabrina; Gimpl, Gerald; Deiml, Tobias; Rammes, Gerhard; Lambert, Jeremy J; Zieglgänsberger, Walter; Holsboer, Florian; Rupprecht, Rainer

    2005-11-01

    Despite different chemical structure and pharmacodynamic signaling pathways, a variety of antidepressants and antipsychotics inhibit ion fluxes through 5-HT3 receptors in a noncompetitive manner with the exception of the known competitive antagonists mirtazapine and clozapine. To further investigate the mechanisms underlying the noncompetitive inhibition of the serotonin-evoked cation current, we quantified the concentrations of different types of antidepressants and antipsychotics in fractions of sucrose flotation gradients isolated from HEK293 (human embryonic kidney 293) cells stably transfected with the 5-HT3A receptor and of N1E-115 neuroblastoma cells in relation to the localization of the 5-HT3 receptor protein within the cell membrane. Western blots revealed a localization of the 5-HT3 receptor protein exclusively in the low buoyant density (LBD) fractions compatible with a localization within raft-like domains. Also, the antidepressants desipramine, fluoxetine, and reboxetine and the antipsychotics fluphenazine, haloperidol, and clozapine were markedly enriched in LBD fractions, whereas no accumulation occurs for mirtazapine, carbamazepine, moclobemide, and risperidone. The concentrations of psychopharmacological drugs within LBD fractions was strongly associated with their inhibitory potency against serotonin-induced cation currents. The noncompetitive antagonism of antidepressants at the 5-HT3 receptor was not conferred by an enhancement of receptor internalization as shown by immunofluorescence studies, assessment of receptor density in clathrin-coated vesicles, and electrophysiological recordings after coexpression of a dominant-negative mutant of dynamin I, which inhibits receptor internalization. In conclusion, enrichment of antidepressants and antipsychotics in raft-like domains within the cell membrane appears to be crucial for their antagonistic effects at ligand-gated ion channels such as 5-HT3 receptors. PMID:16267227

  7. Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice

    Science.gov (United States)

    Valecha, Rekha; Dhingra, Dinesh

    2016-01-01

    Introduction: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in unstressed mice and to explore its mechanism of action. Methods: The seed oil (50, 100, and 200 mg/kg, PO) and fluoxetine per se were administered for 14 successive days to Swiss young albino mice. On the 14th day, 60 min after drug administration, animals were subjected to Tail Suspension Test (TST) and Forced Swim Test (FST). The mechanism of action was also studied. Results: The oil significantly decreased immobility period of mice in both tail suspension test and forced swim test, indicating its significant antidepressant-like activity. The efficacy was found to be comparable to fluoxetine (P<0.0001). ED50 value of celastrus seed oil using FST and TST were 17.38 and 31.62 mg/kg, respectively. The oil did not show any significant effect on locomotor activity. It significantly inhibited brain MAO–A activity and decreased plasma corticosterone levels. Sulpiride (selective D2-receptor antagonist), p-CPA (tryptophan hydroxylase inhibitor), and baclofen (GABAB agonist) significantly attenuated the oil-induced antidepressant-like effect, when assessed during TST. Discussion: Celastrus paniculatus seed oil produced significant antidepressant-like effect in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors; as well as inhibition of MAO–A activity and decrease in plasma corticosterone levels. PMID:27303599

  8. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    OpenAIRE

    Bahareh Amin; Alireza Nakhsaz; Hossein Hosseinzadeh

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effe...

  9. Species-scanning mutagenesis of the serotonin transporter reveals residues essential in selective, high-affinity recognition of antidepressants

    DEFF Research Database (Denmark)

    Mortensen, O V; Kristensen, A S; Wiborg, O

    2001-01-01

    The serotonin transporter (SERT) is a high-affinity sodium/chloride-dependent neurotransmitter transporter responsible for reuptake of serotonin from the extracellular space. SERT is a selective target of several clinically important antidepressants. In a cross-species analysis comparing human and...... antidepressants citalopram, fluoxetine, paroxetine and imipramine were several-fold higher at hSERT compared with bSERT. No species selectivity was observed for the antidepressants fluvoxamine, and sertraline or for the psychostimulants cocaine, the cocaine analogue beta-carbomethoxy-3beta-(4-iodophenyl...

  10. 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

  11. Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test.

    Science.gov (United States)

    Kawaura, Kazuaki; Miki, Risa; Shima, Eriko; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2010-09-13

    Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40mg/kg i.p. significantly reduced immobility. At 40mg/kg i.p., it increased climbing behavior. Even at 40mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect. PMID:20621160

  12. Vortioxetine (Brintellix®) and levomilnacipran (Fetzima®): the two newest additions to the antidepressant formulary.

    Science.gov (United States)

    Roman, Marian W; Wilkinson, Shannon M

    2014-12-01

    In the final months of 2013, the US Food and Drug Administration approved two new antidepressant formulations. This column presents a review of the pertinent literature on both: vortioxetine (Brintellix(®)) and levomilnacipran (Fetzima(®)). PMID:25426751

  13. 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

  14. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus

    OpenAIRE

    Vahdati Hassani, Faezeh; Naseri, Vahideh; Razavi, BiBi Marjan; Mehri, Soghra; Abnous, Khalil; Hosseinzadeh, Hossein

    2014-01-01

    Background Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein...

  15. Evaluation of anti-depressant and anxiolytic activity of Rasayana Ghana Tablet (A compound Ayurvedic formulation) in albino mice

    OpenAIRE

    Deole, Yogesh S.; Chavan, Sulakshan S.; Ashok, B. K.; Ravishankar, B.; Thakar, A.B.; Chandola, H. M.

    2011-01-01

    In recent years, many Ayurvedic formulations are being researched to provide an effective antidepressant and anxiolytic drug in the field of psycho-pharmacology. The present study was planned to evaluate the anti-depressant and anxiolytic activity of Rasayana Ghana Tablet comprising three herbs Guduchi (Tinospora cordifolia Miers), Aamalaki (Emblica officinalis Garten) (RGT) and Gokshura (Tribulus terrestris Linn). Swiss albino mice were divided into four groups of six animals each, comprisin...

  16. The Comparison of Efficacy of Tricyclic Antidepressant with and without Non Steroidal Anti Inflammatory Drugs in Chronic Low Back Pain

    OpenAIRE

    A.R. Yavarikia

    2007-01-01

    Introduction & Objectives: Low back pain (LBP) is one of common medical problems with several accepted medical modalities such as drugs, physiotherapy, surgery, etc. We studied the efficacy of tricyclic antidepressant (TCA), and tricyclic antidepressant plus non steroidal anti inflammatory drugs (TCA + NSAID) in 200 patients with chronic LBP. Materials & Methods: In an experimental clinical trial study on patients with chronic low back pain without organic findings, patients were divided in t...

  17. Evaluation of anti-depressant effect of lemon grass (Cymbopogon citratus) in albino mice

    OpenAIRE

    Sujata Dudhgaonkar; Manali Mahajan; Swapnil Deshmukh; Pallavi Admane; Huma Khan

    2014-01-01

    Background: Depression is a common serious psychiatric disorder and the available anti-depressant treatments are associated with many unwanted side-effects. Thus, various herbal products have been tried. The advantages of herbal treatments would include its complementary nature to the conventional treatment, thus making the latter a safer and cheaper option for depressive disorders. The objective of the present study was to evaluate the anti-depressant activity of lemon grass (Cymbopogon citr...

  18. Evaluation of the Anxiolytic and Antidepressant Effects of Alcoholic Extract of Kaempferia parviflora in Aged Rats

    OpenAIRE

    Jintanaporn Wattanathorn; Prasert Pangpookiew; Kittisak Sripanidkulchai; Supaporn Muchimapura; Bungorn Sripanidkuchai

    2007-01-01

    To date, the search for novel pharmacotherapy from medicinal plants for psychiatric illnesses has significantly progressed. The present study was performed to evaluate the anxiolytic and antidepressant like activities of the K.parviflora rhizome extract. Aged male Wistar rats were orally administered the alcoholic extract of this plant at various doses ranging from 100, 200 and 300 mg kgË1 BW once daily for 7 days. The anxiolytic and antidepressant activities were performed after both single ...

  19. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF

    OpenAIRE

    Laura L. Hurley; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol; Tizabi, Yousef

    2012-01-01

    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in ant...

  20. The High-Affinity Binding Site for Tricyclic Antidepressants Resides in the Outer Vestibule of the Serotonin TransporterⓈ

    OpenAIRE

    Sarker, Subhodeep; Weissensteiner, René; Steiner, Ilka; Sitte, Harald H; Ecker, Gerhard F.; Freissmuth, Michael; Sucic, Sonja

    2010-01-01

    The structure of the bacterial leucine transporter from Aquifex aeolicus (LeuTAa) has been used as a model for mammalian Na+/Cl−-dependent transporters, in particular the serotonin transporter (SERT). The crystal structure of LeuTAa liganded to tricyclic antidepressants predicts simultaneous binding of inhibitor and substrate. This is incompatible with the mutually competitive inhibition of substrates and inhibitors of SERT. We explored the binding modes of tricyclic antidepressants by homolo...

  1. Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

    OpenAIRE

    Murrough, James W.; Burdick, Katherine E.; Levitch, Cara F.; Perez, Andrew M; Brallier, Jess W; Chang, Lee C.; Foulkes, Alexandra; Charney, Dennis S.; Mathew, Sanjay J.; Iosifescu, Dan V.

    2014-01-01

    The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current stud...

  2. Chemical dampening of Ly6Chi monocytes in the periphery produces anti-depressant effects in mice

    OpenAIRE

    Xiao Zheng; Sijing Ma; An Kang; Mengqiu Wu; Lin Wang; Qiong Wang; Guangji Wang; Haiping Hao

    2016-01-01

    The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6Chi monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly...

  3. Neurogenomic Evidence for a Shared Mechanism of the Antidepressant Effects of Exercise and Chronic Fluoxetine in Mice

    OpenAIRE

    Huang, Guo-Jen; Ben-David, Eyal; Tort Piella, Agnès; Edwards, Andrew; Flint, Jonathan; Shifman, Sagiv

    2012-01-01

    Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug – fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The ...

  4. Hippocampal-Dependent Antidepressant Action of the H3 Receptor Antagonist Clobenpropit in a Rat Model of Depression

    OpenAIRE

    Femenía, Teresa; Magara, Salvatore; DuPont, Caitlin M.; Lindskog, Maria

    2015-01-01

    Background: Histamine is a modulatory neurotransmitter regulating neuronal activity. Antidepressant drugs target modulatory neurotransmitters, thus ultimately regulating glutamatergic transmission and plasticity. Histamine H3 receptor (H3R) antagonists have both pro-cognitive and antidepressant effects; however, the mechanism by which they modulate glutamate transmission is not clear. We measured the effects of the H3R antagonist clobenpropit in the Flinders Sensitive Line (FSL), a rat model ...

  5. Effectiveness and safety of antidepressants for ADHD in population between 6 and 19 years: a systematic review

    OpenAIRE

    José Calleja; José Uribarri

    2012-01-01

    Introduction: Attention deficit hyperactivity disorder (ADHD) is generally treated with pharmacologic and non-pharmacologic interventions. Pharmacological treatment is necessary for most patients. Antidepressants are an option so it is important to know about their effectiveness and safety. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of antidepressants in the treatment of ADHD in the 6-19 year-old population. Methods: A systematic ...

  6. Study protocol for the randomised controlled trial: Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study)

    OpenAIRE

    McAllister-Williams, R Hamish; Smith, Eleanor; Anderson, Ian M.; Barnes, Jane; Gallagher, Peter; Grunze, Heinz CR; Haddad, Peter M; House, Allan O; Hughes, Tom; Lloyd, Adrian J; McColl, Elaine MM; Pearce, Simon HS; Siddiqi, Najma; Sinha, Baxi; Speed, Chris

    2013-01-01

    Background Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake ...

  7. The effects of maternal depression and use of antidepressants during pregnancy on risk of a child small for gestational age

    DEFF Research Database (Denmark)

    Jensen, Hans Mørch; Grøn, Randi; Lidegaard, Ojvind; Pedersen, Lars Henning; Andersen, Per Kragh; Kessing, Lars Vedel

    2013-01-01

    Use of antidepressants during pregnancy has been associated with an increased rate of children small for gestational age (SGA), but it is unclear whether this is due to an effect of the underlying depressive disorder.......Use of antidepressants during pregnancy has been associated with an increased rate of children small for gestational age (SGA), but it is unclear whether this is due to an effect of the underlying depressive disorder....

  8. Antidepressant efficacy of high and low frequency transcranial magnetic stimulation in the FSL/FRL genetic rat model of depression.

    Science.gov (United States)

    Hesselberg, Marie Louise; Wegener, Gregers; Buchholtz, Poul Erik

    2016-11-01

    Repetitive Magnetic Stimulation (rTMS) has appeared to be a potential non-invasive antidepressant method, which implies non-convulsive focal stimulation of the brain through a time varying magnetic field. The antidepressant potential of rTMS has been supported by animal studies showing a number of interesting similarities between magnetic stimulation and electroconvulsive stimulation (ECS). Despite these positive results, this method still contains many unknown issues. Importantly, there are fundamental uncertainties concerning the optimal combination of stimulus parameters (frequency, intensity, duration, and number of pulses) to obtain an antidepressant effect. Therefore, the present study aimed to qualify the choice of rTMS stimulus frequency in a well-validated genetic animal model of depression, the FSL/FRL rats. We compared the antidepressant effect of low frequency, high frequency rTMS and ECS to sham treatment in FRL and FSL rats using 6 parallel groups. We used the Forced Swim Test and the Open Field Test to screen the depression-like state in rats. We found that both the high frequency and the low frequency rTMS resulted in a significant antidepressant effect. However, this effect was inferior to the effect of ECS. The low frequency and high frequency groups, which received the same total impulse load and stimulus intensity, did not differ with respect to antidepressant efficacy in this study. In conclusion, this study provides robust evidence that both rTMS interventions are efficacious, although not as efficient as ECS. PMID:27473004

  9. Investigating nitric oxide signalling involvement in the antidepressant action of ketamine

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina;

    2012-01-01

    Stress-induced excessive glutamate transmission at N-methyl-D-aspartate receptors (NMDA-R’s) may underlie a primary mechanism in the physiology that leads to depression, and ketamine, an NMDA-R antagonist, has been shown to rapidly relieve depression in humans. A number of downstream mechanisms...... have been suggested to mediate the antidepressant action of ketamine, including the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), protein kinase B (or Akt) and the mammalian target of rapamycin (mTOR). However, the mechanism(s) that are affected immediately downstream of NMDA......-R’s remain unclear. Neuronal nitric oxide synthase (nNOS) is directly coupled to and activated by NMDA-R’s, and the uncoupling of the nNOS-NMDA-R complex prevents NMDA-R-mediated excitotoxicity. Therefore, we investigated whether the antidepressant mechanism of ketamine involves the inhibition of nitric...

  10. 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

    A total of 219 inpatients with a DSM-III diagnosis of major depression, 150 women and 69 men, were followed prospectively for 3-10 years and mortality was recorded. The patients were previous participants in psychopharmacological multicenter trials, which were carried out for the purpose 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...... according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had a...

  11. 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

    A total of 219 inpatients with a DSM-III diagnosis of major depression, 150 women and 69 men, were followed prospectively for 3-10 years and mortality was recorded. The patients were previous participants in psychopharmacological multicenter trials, which were carried out for the purpose of...... according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had a...... 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...

  12. Two cellular hypotheses explaining the initiation of ketamine's antidepressant actions: Direct inhibition and disinhibition.

    Science.gov (United States)

    Miller, Oliver H; Moran, Jacqueline T; Hall, Benjamin J

    2016-01-01

    A single, low dose of ketamine evokes antidepressant actions in depressed patients and in patients with treatment-resistant depression (TRD). Unlike classic antidepressants, which regulate monoamine neurotransmitter systems, ketamine is an antagonist of the N-methyl-D-aspartate (NMDA) family of glutamate receptors. The effectiveness of NMDAR antagonists in TRD unveils a new set of targets for therapeutic intervention in major depressive disorder (MDD) and TRD. However, a better understanding of the cellular mechanisms underlying these effects is required for guiding future therapeutic strategies, in order to minimize side effects and prolong duration of efficacy. Here we review the evidence for and against two hypotheses that have been proposed to explain how NMDAR antagonism initiates protein synthesis and increases excitatory synaptic drive in corticolimbic brain regions, either through selective antagonism of inhibitory interneurons and cortical disinhibition, or by direct inhibition of cortical pyramidal neurons. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID:26211972

  13. Elevated plasma fibrinogen, psychological distress, antidepressant use, and hospitalization with depression

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

    2013-01-01

    OBJECTIVES: Low-grade systemic inflammation may contribute to the development of depression. We tested the hypothesis that elevated plasma levels of the inflammatory marker fibrinogen are associated with psychological distress, use of antidepressant medication, and with hospitalization......, and hospitalization with depression (p-trend 2×10(-11) to 5×10(-95)). Furthermore, when different classes of antidepressant medication were examined, a stepwise increase in fibrinogen percentile categories was associated with a stepwise increase in risk of use of Selective Serotonin Reuptake Inhibitors and Tricyclic...... with depression in the general population. METHODS: We examined 73,367 20-100 year old men and women from two large population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study. We measured plasma fibrinogen and recorded symptoms of psychological distress, use...

  14. Changes in presynaptic release, but not reuptake, of bioamines induced by long-term antidepressant treatment

    International Nuclear Information System (INIS)

    This paper describes an investigation into the effect of long-term administration of antidepressants on neuronal uptake of NA and 5-HT and on their release, induced by electrical stimulation, in rat brain slices. The effects of the test substances on neuronal uptake of 14C-NA and 3H-5-HT by the slices was investigated. Values of IC50 and EC2 were found and compared in the experiments and control. The inhibitory effect of clonidine (10-4 M) and of 5-HT (10-5 M) on presynaptic release of 14C-NA and 3H-5-HT also was studied in brain slices from intact rats and rats treated for two weeks with antidepressants

  15. Comparison of the kinetic interactions of the neuroleptics perphenazine and zuclopenthixol with tricyclic antidepressives.

    Science.gov (United States)

    Linnet, K

    1995-06-01

    Using data from a therapeutic drug monitoring database, kinetic interactions between the neuroleptics zuclopenthixol and perphenazine and tricyclic antidepressives were studied. Out of 290 patients monitored for amitriptyline and 611 patients monitored for nortriptyline, 77 patients were comedicated with perphenazine and 50 patients with zuclopenthixol. Comedication with perphenazine increased the median steady-state serum concentration to daily dose ratio (C/D) of nortriptyline by 30-45%, whereas the median C/D of amitriptyline was unaffected. On the contrary, median C/D values of nortriptyline and amitriptyline were not significantly influenced by comedication with zuclopenthixol. Thus, in accordance with previous studies, perphenazine increases the concentration of tricyclic antidepressives to a moderate extent. Zuclopenthixol, on the other hand, does not exert any impact under routine therapeutic drug monitoring, even though the drug is known to partly depend on metabolism by the isozyme cytochrome P450 2D6. PMID:7624929

  16. Screening of the antidepressant components in aqueous extract of detoxified cottonseeds

    International Nuclear Information System (INIS)

    Objective: To screen the antidepressant components in aqueous extract of detoxified cottonseeds (CTN). Methods: The synaptic membrane of rat cerebral cortex was extracted and incubated with CTN or its five flavonoid compounds (CTN-4, 7, 8, 9, 10) respectively. The adenylyl cyclase (AC) activity was measured by radioimmunoassay. Results: Just like the positive drug buspirone, a 5-HT1A receptor partial agonist, CTN and its five flavonoid compounds all activated AC in synaptic membrane in a dose-dependent manner, with compound CTN-8 being the most effective. Conclusion: The CTN-8, quercetin-3-O-apionyl-rutinoside, may be one of the most effective antidepressant components in CTN, and be a 5-HT1A receptor agonist. (authors)

  17. Enhanced sensitivity of muscarinic cholinergic receptor associated with dopaminergic receptor subsensitivity after chronic antidepressant treatment

    International Nuclear Information System (INIS)

    The chronic effects of antidepressant treatment on striatal dopaminergic (DA) and muscarinic cholinergic (mACh) receptors of the rat brain have been examined comparatively in this study using 3H-spiroperidol (3H-SPD) and 3H-quinuclidinyl benzilate (3H-QNB) as the respective radioactive ligands. Imipramine and desipramine were used as prototype antidepressants. Although a single administration of imipramine or desipramine did not affect each receptor sensitivity, chronic treatment with each drug caused a supersensitivity of mACh receptor subsequent to DA receptor subsensitivity. Furthermore, it has been suggested that anti-mACh properties of imipramine or desipramine may not necessarily be related to the manifestation of mACh receptor supersensitivity and that sustained DA receptor subsensitivity may play some role in the alterations of mACh receptor sensitivity

  18. Social functioning: should it become an endpoint in trials of antidepressants?

    Science.gov (United States)

    Bech, Per

    2005-01-01

    DSM-IV has recommended use of the Social and Occupational Functioning Scale (SOFAS) as a clinician-rated global assessment scale for measuring social functioning; this scale is analogous to the Clinical Global Impression (CGI) scale traditionally used as a secondary outcome measure in patients with depressive symptoms. However, we believe that health-related quality of life is the most appropriate indicator of social functioning when considering this dimension as an endpoint in clinical trials of antidepressants. As health-related quality of life is a purely subjective measure, patient-rated questionnaires have been found to be most important in this context. In this respect, the Sheehan Disability Scale has been recommended as the most relevant global self-reported assessment of social functioning in trials of antidepressants.A review of questionnaires found that the three most frequently used scales selectively directed at obtaining information about social functioning in trials of antidepressants are the Social Adjustment Scale - Self Report (SAS-SR), the Social Adaptation Self-Evaluation Scale (SASS) and the Short-Form Health Survey (SF-36). However, the number of placebo-controlled trials of antidepressants that have used these scales is still too limited to allow comparisons in terms of responsiveness.Health-related quality of life includes dimensions other than social functioning, e.g. physical health and mental health (including both cognitive and affective problems). The SF-36 includes subscales relating to physical and mental health, which, like the social functioning subscales, are measured in terms of degrees of well being. Another quality-of-life questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), covers social, mental and physical problems, in this case measured in terms of degrees of satisfaction. Recently, the Q-LES-Q has been reduced from a comprehensive scale including 60-92 items to a brief version including 15

  19. DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses.

    Science.gov (United States)

    Vialou, Vincent; Robison, Alfred J; Laplant, Quincey C; Covington, Herbert E; Dietz, David M; Ohnishi, Yoshinori N; Mouzon, Ezekiell; Rush, Augustus J; Watts, Emily L; Wallace, Deanna L; Iñiguez, Sergio D; Ohnishi, Yoko H; Steiner, Michel A; Warren, Brandon L; Krishnan, Vaishnav; Bolaños, Carlos A; Neve, Rachael L; Ghose, Subroto; Berton, Olivier; Tamminga, Carol A; Nestler, Eric J

    2010-06-01

    In contrast with the many studies of stress effects on the brain, relatively little is known about the molecular mechanisms of resilience, the ability of some individuals to escape the deleterious effects of stress. We found that the transcription factor DeltaFosB mediates an essential mechanism of resilience in mice. Induction of DeltaFosB in the nucleus accumbens, an important brain reward-associated region, in response to chronic social defeat stress was both necessary and sufficient for resilience. DeltaFosB induction was also required for the standard antidepressant fluoxetine to reverse behavioral pathology induced by social defeat. DeltaFosB produced these effects through induction of the GluR2 AMPA glutamate receptor subunit, which decreased the responsiveness of nucleus accumbens neurons to glutamate, and through other synaptic proteins. Together, these findings establish a previously unknown molecular pathway underlying both resilience and antidepressant action. PMID:20473292

  20. No interactions between genetic polymorphisms and stressful life events on outcome of antidepressant treatment

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj;

    2009-01-01

    Genetic polymorphisms seem to influence the response on antidepressant treatment and moderate the impact of stress on depression. The present study aimed to assess, whether allelic variants and stressful life events interact on the clinical outcome of depression. In a sample of 290 systematically...... recruited patients diagnosed with a single depressive episode according to ICD-10, we assessed the outcome of antidepressant treatment and the presence of stressful life events in a 6-month period preceding onset of depression by means of structured interviews. Further, we genotyped nine polymorphisms...... in the genes encoding the serotonin transporter, brain derived neurotrophic factor, catechol-O-methyltransferase, angiotensin converting enzyme, tryptophan hydroxylase, and the serotonin receptors 1A, 2A, and 2C. We found no evidence that the effects of the genetic polymorphisms on treatment outcome were...

  1. Research progress of antidepressants%抗抑郁药的研究新进展

    Institute of Scientific and Technical Information of China (English)

    李亮亮

    2014-01-01

    Depression is becoming a serious global problem.Now antidepressants are divided into four types:monoamine oxidase inhibitors(MAOIs),tricyclicantide pressants(TCAs),selective serotonin reuptake inhibitors (SS-RIs) and new antidepressants.%抑郁症正成为一个严重的全球问题。目前抗抑郁药物分四大类:单胺氧化酶抑制剂(Monoamine oxidase inhibitors,MAOIs)、三环类药物(Tricyclicantide pressants,TCAs)、选择性5-色胺再摄取抑制剂(Selective serotonin reuptake inhibitors,SSRIs)、新型抗抑郁药。

  2. LeuT-Desipramine Structure Reveals How Antidepressants Block Neurotransmitter Reuptake

    Energy Technology Data Exchange (ETDEWEB)

    Zhou,Z.; Zhen, J.; Karpowich, N.; Goetz, R.; Law, C.; Reith, M.; Wang, D.

    2007-01-01

    Tricyclic antidepressants exert their pharmacological effect -- inhibiting the reuptake of serotonin, norepinephrine, and dopamine -- by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.

  3. Elevated Risk of Preeclampsia in Pregnant Women With Depression: Depression or Antidepressants?

    OpenAIRE

    Palmsten, Kristin; Setoguchi, Soko; Margulis, Andrea V; Patrick, Amanda R.; Hernández-Díaz, Sonia

    2012-01-01

    A previous study suggested an increased risk of preeclampsia among women treated with selective serotonin reuptake inhibitors (SSRIs). Using population-based health-care utilization databases from British Columbia (1997–2006), the authors conducted a study of 69,448 pregnancies in women with depression. They compared risk of preeclampsia in women using SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) between gestational weeks 10 and 20 with risk...

  4. ANTIDEPRESSANT RESPONSE TO PARTIAL SLEEP DEPRIVATION IN UNIPOLAR DEPRESSION IS NOT RELATED TO STATE ANXIETY

    OpenAIRE

    Clark, Camellia P.; Golshan, Shahrokh

    2008-01-01

    One night of total or partial sleep deprivation (SD) produces a temporary remission in up to 60% of patients with major depression, yet mechanisms remain unclear. We investigated whether the antidepressant effects of SD are caused, even partially, by an improvement in anxiety. As part of a functional magnetic resonance imaging study, 19 unmedicated major depression patients and eight controls completed the Spielberger State/Trait Anxiety Inventory (STAI) (state version) at baseline and sleep-...

  5. Does amygdalar perfusion correlate with antidepressant response to partial sleep deprivation in major depression?

    OpenAIRE

    Clark, Camellia P.; Brown, Gregory G.; Archibald, Sarah L.; Fennema-Notestine, Christine; Braun, Deborah R.; Thomas, Linda S.; Sutherland, Ashley N.; Gillin, J. Christian

    2005-01-01

    This study used functional MRI (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: (1) baseline perfusion in right and left amygdalae will be greater in responders than in nonresponders; (2) following partial sleep deprivation (PSD), perfusion in responders’ right and left amygdalae would decrease. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI ...

  6. Purchases of Prescription Antidepressants in the Swedish Population in Relation to Major Workplace Downsizing.

    Science.gov (United States)

    Magnusson Hanson, Linda L; Westerlund, Hugo; Chungkham, Holendro Singh; Vahtera, Jussi; Sverke, Magnus; Alexanderson, Kristina

    2016-03-01

    Organizational downsizing may be a risk factor for morbidity among both the displaced and those who remain in work. However, the knowledge is limited regarding its impact on clinically relevant mental health problems. Our objective was to investigate purchases of prescription antidepressants across 5 years in relation to workplace downsizing. We studied all Swedish residents 2004 throughout 2010, 22-54 years old in 2006, gainfully employed, and with a stable labor market position up to 2006. People primarily employed at a workplace with ≥18% staff reduction were considered exposed to major downsizing (in 2006-2007, 2007-2008, or 2008-2009). We applied repeated measures regression analyses through generalized estimating equations, calculating odds of any purchase of prescription antidepressants (inferred from the prescribed drug register) within five 12-month periods from 2 years before to 2 years after the period of major downsizing and compared the trends for newly exposed (n = 632,500) and unexposed (n = 1,021,759) to major downsizing. The odds of purchasing prescription antidepressants for exposed increased more than for nonexposed, mainly peridownsizing (1 year before to 1 year after), and postdownsizing (1 year after to 2 years after) for survivors (odds ratio 1.24 vs. 1.14 peridownsizing and 1.12 vs. 1.00 postdownsizing) and those changing workplace (odds ratio 1.22 vs. 1.14 peridownsizing and 1.10 vs. 1.00 postdownsizing) with no previous sickness absence or disability pension (≥7% more than unexposed peri- and postdownsizing). This large-scale study indicates that downsizing is associated with a slight increase in the odds of purchasing prescription antidepressants among people without previous sickness absence or disability pension. PMID:26501153

  7. Identification of primary care patients at risk of nonadherence to antidepressant treatment

    OpenAIRE

    Ann-Charlotte Åkerblad; Finn Bengtsson; Margareta Holgersson; Lars von Knorring; Lisa Ekselius

    2008-01-01

    Ann-Charlotte Åkerblad1, Finn Bengtsson2, Margareta Holgersson3, Lars von Knorring1, Lisa Ekselius11Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala University, Uppsala, Sweden; 2Division of Clinical Pharmacology, Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 3Quintiles AB, Uppsala, SwedenIntroduction: Poor adherence to antidepressant treatment is common, and results in increased disability and c...

  8. Antidepressants stimulate hippocampal neurogenesis by inhibiting p21 expression in the subgranular zone of the hipppocampus.

    Directory of Open Access Journals (Sweden)

    Robert N Pechnick

    Full Text Available The relationships among hippocampal neurogenesis, depression and the mechanism of action of antidepressant drugs have generated a considerable amount of controversy. The cyclin-dependent kinase (Cdk inhibitor p21(Cip1 (p21 plays a crucial role in restraining cellular proliferation and maintaining cellular quiescence. Using in vivo and in vitro approaches the present study shows that p21 is expressed in the subgranular zone of the dentate gyrus of the hippocampus in early neuronal progenitors and in immature neurons, but not in mature neurons or astroglia. In vitro, proliferation is higher in neuronal progenitor cells derived from p21-/- mice compared to cells derived from wild-type mice. Proliferation is increased in neuronal progenitor cells after suppression of p21 using lentivirus expressing short hairpin RNA against p21. In vivo, chronic treatment with the non-selective antidepressant imipramine as well as the norepinephrine-selective reuptake inhibitor desipramine or the serotonin-selective reuptake inhibitor fluoxetine all decrease p21 expression, and this was associated with increased neurogenesis. Chronic antidepressant treatment did not affect the expression of other Cdk inhibitors. Untreated p21-/- mice exhibit a higher degree of baseline neurogenesis and decreased immobility in the forced swim test. Although chronic imipramine treatment increased neurogenesis and reduced immobility in the forced swim test in wild-type mice, it reduced neurogenesis and increased immobility in p21-/- mice. These results demonstrate the unique role of p21 in the control of neurogenesis, and support the hypothesis that different classes of reuptake inhibitor-type antidepressant drugs all stimulate hippocampal neurogenesis by inhibiting p21 expression.

  9. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

    OpenAIRE

    Rafael G. dos Santos; Osório, Flávia L.; José Alexandre S. Crippa; Hallak, Jaime E. C.

    2016-01-01

    Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies ...

  10. Identification of antidepressant drug leads through the evaluation of marine natural products with neuropsychiatric pharmacophores

    OpenAIRE

    Diers, Jeffrey A.; Ivey, Kelly D.; El-Alfy, Abir; Shaikh, Jamaluddin; Wang, Jiajia; Kochanowska, Anna J.; Stoker, John F.; Mark T. Hamann; Matsumoto, Rae R.

    2007-01-01

    The marine environment is a valuable resource for drug discovery due to its diversity of life and associated secondary metabolites. However, there is very little published data on the potential application of marine natural products to treat neuropsychiatric disorders. Many natural products derived from chemically defended organisms in the marine environment have pharmacophores related to serotonin or clinically utilized antidepressant drugs. Therefore, in the present study, compounds selecte...

  11. Neurobiological aspects of depressive disorder and antidepressant treatment: role of glia

    Czech Academy of Sciences Publication Activity Database

    Páv, M.; Kovářů, H.; Fišerová, Anna; Havrdová, E.; Lisá, Věra

    2008-01-01

    Roč. 57, č. 2 (2008), s. 151-164. ISSN 0862-8408 R&D Projects: GA ČR GA524/05/0267; GA AV ČR IAA500200620 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : major depression * mood disorder * antidepressant Subject RIV: EC - Immunology Impact factor: 1.653, year: 2008

  12. Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages.

    Science.gov (United States)

    Nazimek, Katarzyna; Kozlowski, Michael; Bryniarski, Pawel; Strobel, Spencer; Bryk, Agata; Myszka, Michal; Tyszka, Anna; Kuszmiersz, Piotr; Nowakowski, Jaroslaw; Filipczak-Bryniarska, Iwona

    2016-08-01

    Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive

  13. Prevalence and factors associated with off-label antidepressant prescriptions for insomnia

    OpenAIRE

    Lai, Leanne

    2011-01-01

    L Leanne Lai¹, Mooi Heong Tan¹, Yen Chi Lai²¹Department of Sociobehavioral and Administrative Pharmacy, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA; ²Department of Internal Medicine, Golen Hospital, Pintong City, TaiwanBackground: The primary objective of our study was to investigate the prevalence of off-label antidepressant drug use in insomnia. The secondary objective was to compare prescribing patterns between of...

  14. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling

    OpenAIRE

    Hines, D J; Schmitt, L I; Hines, R. M.; Moss, S J; Haydon, P. G.

    2013-01-01

    Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions...

  15. Sustained Neurobehavioral Effects of Exposure to SSRI Antidepressants During Development: Molecular to Clinical Evidence

    OpenAIRE

    Oberlander, TF; Gingrich, JA; Ansorge, MS

    2009-01-01

    Selective serotonin reuptake inhibitor (SSRI) antidepressants are frequently used in the management of antenatal maternal mood disturbances. SSRIs readily cross the placenta and increase central serotonergic tone in the fetus. Given serotonin’s key neurodevelopmental role, such prenatal exposure raises concerns about its impact on child development. Preclinical studies report enduring molecular, physiological, and behavioral consequences of developmental SSRI exposure. In humans, sustained de...

  16. Antinociceptive and antidepressant-like action of endomorphin-2 analogs with proline surrogates in position 2.

    Science.gov (United States)

    Perlikowska, Renata; Piekielna, Justyna; Mazur, Marzena; Koralewski, Robert; Olczak, Jacek; do Rego, Jean-Claude; Fichna, Jakub; Modranka, Jakub; Janecki, Tomasz; Janecka, Anna

    2014-09-01

    In our efforts to develop new candidate drugs with antinociceptive and/or antidepressant-like activity, two novel endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH2) analogs, containing proline surrogates in position 2 were synthesized using commercially available racemic trans-4-phenylpyrrolidine-3-carboxylic acid (4-Ph-β-Pro). The obtained mixture of two diastereoisomeric peptides (2a and 2b) was separated by HPLC and both enantiopure analogs were used in the in vitro and in vivo studies. To assign the absolute configuration to the 4-Ph-β-Pro residues in both peptides, the stereoselective synthesis of (3R,4S)-4-phenylpyrrolidine-3-carboxylic acid was performed and this enantiomer was introduced into position 2 of EM-2 sequence. Based on the HPLC retention times we were able to assign the absolute configuration of 4-Ph-β-Pro residues in both peptide analogs. Analog 2a incorporating (3R,4S)-4-Ph-β-Pro residue produced strong analgesia in mice after intracerebroventricular (icv) administration which was antagonized by the μ-opioid receptor (MOR) antagonist, β-funaltrexamine (β-FNA). This analog also influenced an emotion-related behavior of mice, decreasing immobility time in the forced swimming and tail suspension tests, without affecting locomotor activity. The antidepressant-like effect was reversed by the δ-selective antagonist, naltrindole (NLT) and κ-selective nor-binaltorphimine (nor-BNI). Thus, the experiments with selective opioid receptor antagonists revealed that analgesic action of analog 2a was mediated through the MOR, while the δ- and κ-receptors (DOR and KOR, respectively) were engaged in the antidepressant-like activity. Analog 2b with (3S,4R)-4-Ph-β-Pro in position 2 showed no antinociceptive or antidepressant-like activity in animal studies. PMID:25047937

  17. Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action

    OpenAIRE

    Cao, Jun-Li; Covington, Herbert E.; Friedman, Allyson K.; Wilkinson, Matthew B.; Walsh, Jessica J.; Cooper, Donald C.; Nestler, Eric J.; Han, Ming-Hu

    2010-01-01

    We previously reported that the activity of mesolimbic dopamine neurons of the ventral tegmental area (VTA) is a key determinant of behavioral susceptibility vs. resilience to chronic social defeat stress. However, this was based solely on ex vivo measurements, and the in vivo firing properties of VTA dopamine neurons in susceptible and resilient mice, as well as the effects of antidepressant treatments, remain completely unknown. Here, we show that chronic (10-day) social defeat stress signi...

  18. Adherence to antidepressant medications: an evaluation of community pharmacists’ counseling practices [Corrigendum

    Directory of Open Access Journals (Sweden)

    Chong WW

    2013-10-01

    Full Text Available Chong WW, Aslani P, Chen TF. Patient Prefer Adherence. 2013;7:813–825.On page 815, Figure 1 should have the following note listed beneath it: "Note: Reprinted from Res Social Adm Pharm, Chong WW, Aslani P, Chen TF, Pharmacist–patient communication on use of antidepressants: A simulated patient study in community pharmacy, Epub, Copyright © 2013, with permission from Elsevier.27"Read the original article

  19. Ion-Selective Membrane Electrode for the Determination of a Novel Phenylpiperazine Antidepressant, Nefazodone

    OpenAIRE

    Erdem, Arzum; ÖZKAN, Dilşat; KERMAN, Kağan; MERİÇ, Burcu

    2000-01-01

    The construction and performance characteristics of ion-selective membrane electrodes for a newly found phenylpiperazine antidepressant, Nefazodone (NFN), based on its ion-pair complexes with phosphotungstate (PT), tetraphenylborate (TPB), tungstosilicate (TS) and reineckate (RN) in a poly(vinyl chloride) (PVC) matrix are described. The best ion-selective electrode for determination of NFN contains NFN-PT as the active material. This electrode exhibits a Nernstian response (62.6 ± 0.4 mV per ...

  20. Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats.

    Science.gov (United States)

    Wollnik, F

    1992-10-01

    Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro 19-6327, a selective MAO type B inhibitor; c) desipramine, a preferential norepinephrine reuptake inhibitor; d) clomipramine and e) fluoxetine, both serotonin reuptake inhibitors; and f) levoprotiline, an atypical antidepressant whose biochemical mechanism is still unknown. Wheel-running activity rhythms were studied in three inbred strains of laboratory rats (ACI, BH, LEW) under constant darkness (DD). Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Chronic treatment with moclobemide and desipramine consistently increased the overall level, as well as the circadian amplitude, of the activity rhythm. Furthermore, the abnormal activity pattern of the LEW strain was changed into a unimodal activity pattern like that of other laboratory rats. The free-running period tau was slightly shortened by moclobemide and dramatically shortened by desipramine. Effects of moclobemide and desipramine treatment on overall activity level and duration were reversed shortly after termination of treatment, whereas long aftereffects were observed for the free-running period. All other substances tested had no systematic effects on the activity rhythms of any of the strains. The fact that moclobemide and desipramine altered the period, amplitude, and pattern of circadian activity rhythms is consistent with the hypothesis that monoaminergic transmitters

  1. Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats

    OpenAIRE

    Wollnik, Franziska

    1992-01-01

    Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro...

  2. A longitudinal functional neuroimaging study in medication-naive depression after antidepressant treatment.

    Directory of Open Access Journals (Sweden)

    Hiroi Tomioka

    Full Text Available Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS as a tool in assisting the diagnosis of major depressive disorder (MDD; however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC. We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover, the correlation analysis indicates that the NIRS signals before the initiation of treatment may be a biological marker to predict patient's clinical response to antidepressant treatment. The present study provides further evidence to support a potential application of NIRS for the diagnosis and treatment of depression.

  3. Sociodemographic and clinical predictors of compliance with antidepressants for depressive disorders: systematic review of observational studies

    OpenAIRE

    Rivero-Santana, Amado; Perestelo-Perez, Lilisbeth; Pérez-Ramos, Jeanette; Serrano-Aguilar, Pedro; De las Cuevas, Carlos

    2013-01-01

    Background The literature shows that compliance with antidepressant treatment is unsatisfactory. Several personal and disease-related variables have been shown to be related to compliance behavior. The objective of this study was to review the literature about sociodemographic and clinical predictors of compliance in patients with depressive disorders. Methods The Medline, Embase, Cochrane Central, PsycInfo, and Cinahl databases were searched until May 2012. Studies that analyzed sociodemogra...

  4. An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice

    OpenAIRE

    Sheline, Yvette I.; West, Tim; Yarasheski, Kevin; Swarm, Robert; Jasielec, Mateusz S.; Fisher, Jonathan R.; Ficker, Whitney D.; Yan, Ping; Xiong, Chengjie; Frederiksen, Christine; Grzelak, Monica V.; Chott, Robert; Bateman, Randall J.; Morris, John C.; Mark A. Mintun

    2014-01-01

    Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor (SSRI), decreased Aβ in brain interstitial fluid (ISF) in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested th...

  5. Antidepressant Effects of Ketamine on Depression-like Behavior in Juvenile Mice after Neonatal Dexamethasone Exposure

    OpenAIRE

    Li, Su-xia; Zhang, Ji-chun; Wu, Jin; Hashimoto, Kenji

    2014-01-01

    Objective Pediatric depression is associated with significant functional impairment at school and at work. Recently, we reported on depression-like behavior in juvenile mice neonatally exposed to dexamethasone (DEX) as a potential animal model for pediatric depression. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has promoted rapid and long-lasting antidepressant effects in patients with treatment-resistant major depression. This study was conducted to examine whether ketamine...

  6. Antidepressant-like Responses to Lithium in Genetically Diverse Mouse Strains

    OpenAIRE

    Adem CAN; Blackwell, Robert A.; Piantadosi, Sean C.; Dao, David T.; O’Donnell, Kelley C.; Gould, Todd D.

    2011-01-01

    A mood stabilizing and antidepressant response to lithium is only found in a subgroup of bipolar disorder and depression patients. Identifying strains of mice that are responsive and non-responsive to lithium may elucidate genomic and other biological factors that play a role in lithium responsiveness. Mouse strains were tested in the forced swim, tail suspension, and open field tests after acute and chronic systemic, and intracerebroventricular and chronic lithium treatments. Serum and brain...

  7. Antidepressants for bipolar disorder: A meta-analysis of randomized, double-blind, controlled trials

    OpenAIRE

    Zhang, Yingli; Yang, Huan; Yang, Shichang; Liang, Wei; DAI, Ping; Wang, Changhong; Zhang, Yalin

    2013-01-01

    OBJECTIVE: To examine the efficacy and safety of short-term and long-term use of antidepressants in the treatment of bipolar disorder. DATA SOURCES: A literature search of randomized, double-blind, controlled trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Controlled Trials databases. The keywords “bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed ma...

  8. Antidepressant-like Effects of Buprenorphine are Mediated by Kappa Opioid Receptors.

    Science.gov (United States)

    Falcon, Edgardo; Browne, Caroline A; Leon, Rosa M; Fleites, Vanessa C; Sweeney, Rachel; Kirby, Lynn G; Lucki, Irwin

    2016-08-01

    Previous studies have identified potential antidepressant effects of buprenorphine (BPN), a drug with high affinity for mu opioid receptor (MORs) and kappa opioid receptors (KORs) and some affinity at delta opioid receptor (DOR) and opioid receptor-like 1 (ORL-1) receptors. Therefore, these studies examined which opioid receptors were involved in BPN's effects on animal behavior tests sensitive to antidepressant drugs. The acute effects of BPN were tested in the forced swim test (FST) using mice with genetic deletion of individual opioid receptors or after pharmacological blockade of receptors. For evaluating the effects of BPN on chronic stress, separate groups of mice were exposed to unpredictable chronic mild stress (UCMS) for 3 weeks and treated with BPN for at least 7 days before behavioral assessment and subsequent measurement of Oprk1, Oprm1, and Pdyn mRNA expression in multiple brain regions. BPN did not reduce immobility in mice with KOR deletion or after pretreatment with norbinaltorphimine, even though desipramine remained effective. In contrast, BPN reduced immobility in MOR and DOR knockout mice and in mice pretreated with the ORL-1 antagonist JTC-801. UCMS reduced sucrose preference, decreased time in the light side of the light/dark box, increased immobility in the FST and induced region-specific alterations in Oprk1, Oprm1, and PDYN mRNA expression in the frontal cortex and striatum. All of these changes were normalized following BPN treatment. The KOR was identified as a key player mediating the effects of BPN in tests sensitive to antidepressant drugs in mice. These studies support further development of BPN as a novel antidepressant. PMID:26979295

  9. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

    Directory of Open Access Journals (Sweden)

    Tozaki-Saitoh Hidetoshi

    2009-04-01

    Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

  10. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

    OpenAIRE

    Osório, Flávia L.; Rafael F. Sanches; Ligia R. Macedo; Rafael G. dos Santos; João P. Maia-de-Oliveira; Lauro Wichert-Ana; Draulio B. de Araujo; Jordi Riba; José A. Crippa; Hallak, Jaime E.

    2015-01-01

    Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were...

  11. Antidepressant use in children and adolescents: Practice touch points to guide paediatricians

    OpenAIRE

    Oberlander, Tim F.; Miller, Anton R

    2011-01-01

    Depression in children and youth is common, and requires an understanding of its developmental character and associated comorbid conditions. Initial treatment of mild depression involves active supportive measures with a focus on symptom reduction and improved daily function. Where pharmacotherapy is warranted, evidence supports the use of selective serotonin reuptake inhibitor (SSRI) antidepressants, particularly fluoxetine, to manage moderate/severe depression. SSRI treatment should include...

  12. The analgesic effect of different antidepressants combined with aspirin on thermally induced pain in Albino mice

    Directory of Open Access Journals (Sweden)

    Abdalla S. Elhwuegi

    2012-04-01

    Full Text Available 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 animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg, imipramine (2.5, 7.5, 15 or 30 mg/kg, fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg, mirtazapine (1.25, 2.5, or 5 mg/kg and a combination of a fixed dose of aspirin (100 mg/kg with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT of the lowest dose (by 23% and the highest dose (by 20%. The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively.Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug.

  13. Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling.

    Science.gov (United States)

    Neis, Vivian Binder; Moretti, Morgana; Bettio, Luis Eduardo B; Ribeiro, Camille M; Rosa, Priscila Batista; Gonçalves, Filipe Marques; Lopes, Mark William; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2016-06-01

    The activation of AMPA receptors and mTOR signaling has been reported as mechanisms underlying the antidepressant effects of fast-acting agents, specially the NMDA receptor antagonist ketamine. In the present study, oral administration of agmatine (0.1mg/kg), a neuromodulator that has been reported to modulate NMDA receptors, caused a significant reduction in the immobility time of mice submitted to the tail suspension test (TST), an effect prevented by the administration of DNQX (AMPA receptor antagonist, 2.5μg/site, i.c.v.), BDNF antibody (1μg/site, i.c.v.), K-252a (TrkB receptor antagonist, 1μg/site, i.c.v.), LY294002 (PI3K inhibitor, 10nmol/site, i.c.v.) or rapamycin (selective mTOR inhibitor, 0.2nmol/site, i.c.v.). Moreover, the administration of lithium chloride (non-selective GSK-3β inhibitor, 10mg/kg, p.o.) or AR-A014418 (selective GSK-3β inhibitor, 0.01μg/site, i.c.v.) in combination with a sub-effective dose of agmatine (0.0001mg/kg, p.o.) reduced the immobility time in the TST when compared with either drug alone. Furthermore, increased immunocontents of BDNF, PSD-95 and GluA1 were found in the prefrontal cortex of mice just 1h after agmatine administration. These results indicate that the antidepressant-like effect of agmatine in the TST may be dependent on the activation of AMPA and TrkB receptors, PI3K and mTOR signaling as well as inhibition of GSK-3β, and increase in synaptic proteins. The results contribute to elucidate the complex signaling pathways involved in the antidepressant effect of agmatine and reinforce the pivotal role of these molecular targets for antidepressant responses. PMID:27061850

  14. Serial Monitoring of Lead aVR in Patients with Prolonged Unconsciousness Following Tricyclic Antidepressant Overdose

    OpenAIRE

    Choi, Kyoung Ho; Lee, Kyoung-Uk

    2008-01-01

    Severe cardiac and neurologic toxicities of tricyclic antidepressant (TCA) overdose have been reported since the introduction of TCAs in 1950s. Despite the decreased numbers of TCA overdoses, the mortality and morbidity rates of TCA overdose have remained constantly high. Clinical manifestations of TCA overdose are characterized by unconsciousness and specific electrocardiography (ECG) abnormalities such as prolongation of the PR and QTc intervals, widening of the QRS duration, and an increas...

  15. Effects of antidepressant fluoxetine (Prozac-TM) on the metabolism of thyroid hormones

    Czech Academy of Sciences Publication Activity Database

    Pavelka, Stanislav

    České Budějovice: -, 2008. s. 60-60. ISBN 80-86313-21-2. [Biochemický sjezd /21./. 14.09.2008-17.09.2008, České Budějovice] Grant ostatní: GA AV ČR(CZ) KJB401630701 Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * antidepressant * metabolism * thyroid hormone Subject RIV: FR - Pharmacology ; Medidal Chemistry

  16. Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures.

    Science.gov (United States)

    Smaga, Irena; Bystrowska, Beata; Gawliński, Dawid; Pomierny, Bartosz; Stankowicz, Piotr; Filip, Małgorzata

    2014-08-01

    The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery. PMID:24652522

  17. Initiation, execution and discontinuation of antidepressant therapy: considerations and decisions of patients

    OpenAIRE

    Geffen, E.C.G. van

    2008-01-01

    Antidepressants have shown to be effective in the treatment of depression and anxiety by reducing symptoms, as well as the risk of relapse and recurrence. Yet, several obstacles have been acknowledged in the process of adequate diagnosis and treatment of patients with these diseases: underrecognition of the health problem by the patient, underconsultation among patients who need treatment, failure to recognise and diagnose the problem by the physician, failure to prescribe drug treatment for ...

  18. Antidepressant-like Effects of Buprenorphine in Rats Are Strain Dependent

    Science.gov (United States)

    Browne, Caroline A.; van Nest, Duncan; Lucki, Irwin

    2014-01-01

    The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains. PMID:25453747

  19. Do Antidepressants Lower the Prevalence of Lithium-associated Hypernatremia in the Elderly? A Retrospective Study

    OpenAIRE

    Rej, Soham; Looper, Karl; Segal, Marilyn

    2013-01-01

    Background Clinically important measures of lithium-induced nephrogenic diabetes insipidus (NDI) such as hypernatremia have not been well-studied. This is especially relevant for the elderly who, in comparison to younger adults, may become symptomatic and require hospitalization with relatively small elevations in sodium levels. We hypothesized that antidepressant use, which has been associated with the syndrome of inappropriate antidiuretic hormone secretion, has a protective effect against ...

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

    DEFF Research Database (Denmark)

    Erlangsen, Annette; Conwell, Yeates

    2014-01-01

    ,720,639 person-years for men and women, respectively. Men aged 50-59 who received antidepressants had a mean suicide rate of 185 (95% confidence interval [CI]: 160-211) per 100,000, whereas for those aged 80+ the rate was 119 (95% CI: 91-146). For women, the corresponding values were 82 (95% CI: 70-94) and 28...

  1. Prediction of antidepressant treatment response from gray matter volume across diagnostic categories.

    Science.gov (United States)

    Sämann, Philipp G; Höhn, David; Chechko, Natalya; Kloiber, Stefan; Lucae, Susanne; Ising, Marcus; Holsboer, Florian; Czisch, Michael

    2013-11-01

    Dysfunctional limbic, paralimbic and prefrontal brain circuits represent neural substrates of major depression that are targeted by pharmacotherapy. In a high resolution structural magnetic resonance imaging (MRI) study we investigated the potential of variability of the cortex volume to predict the response to antidepressant treatment among patients with major depression. We enrolled 167 patients participating in the Munich Antidepressant Response Signature (MARS) study and employed voxel based morphometry to investigate covariation of gray matter (GM) maps with changes of depression severity over 5 weeks. Larger left hippocampal and bilateral posterior cingulate GM volumes and lower right temporolateral GM volumes were associated with beneficial treatment response. Subcallosal/orbitofrontal GM volumes were associated with treatment response mainly through gender-by-region interactions. A hippocampal/temporolateral composite marker proved robust in both first episode and recurrent unipolar patients and in bipolar patients. Compared with 92 healthy controls, abnormally low volumes were only detected in the left hippocampal area, particularly in recurrent unipolar patients. These findings indicate that variability of the cortex volume of specific brain areas is associated with different response to antidepressants. In addition, hippocampal findings recursively link together unfavorable treatment response and progressive hippocampal structural changes in recurrent depression. PMID:23920122

  2. Invasive Cervical Cancer and Antidepressants: A Nationwide Population-Based Study.

    Science.gov (United States)

    Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Liang, Hsin-Yi; Huang, Kuo-You; Chiu, Wei-Che; Lee, Yena; McIntyre, Roger S; Chen, Vincent Chin-Hung

    2015-10-01

    To our knowledge, no prior population-based study has been published wherein the primary aim was to evaluate whether an association between psychotropic drug prescription and cervical cancer exists. Herein we have conducted the first study that primarily aimed to determine the association between antidepressants use and risk of invasive cervical cancer in the general population.This is a population-based study utilizing Taiwan's National Health Insurance Research Database. We identified 26,262 cases with invasive cervical cancer and 129,490 controls. We adopted the conditional logistic regression model as the statistical method and adjusted for potential confounding factors.The prescription of selective serotonin reuptake inhibitors (SSRIs) (adjusted OR = 0.93, 95% CI = 0.84-1.04), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine and bupropion, adjusting for cumulative dose, was not associated with an increased, or decreased, risk for invasive cervical cancer. An association between trazodone prescription and invasive cervical cancer was observed (adjusted OR = 1.22, 95% CI = 1.03-1.43).An association between the major classes of antidepressants and invasive cervical cancer was not observed herein. Our preliminary finding regarding a possible association between trazodone and cervical cancer requires replication. PMID:26496343

  3. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

    Directory of Open Access Journals (Sweden)

    Rafael G. dos Santos

    2016-03-01

    Full Text Available Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline. Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

  4. Evaluation of the Anxiolytic and Antidepressant Effects of Alcoholic Extract of Kaempferia parviflora in Aged Rats

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    Jintanaporn Wattanathorn

    2007-01-01

    Full Text Available To date, the search for novel pharmacotherapy from medicinal plants for psychiatric illnesses has significantly progressed. The present study was performed to evaluate the anxiolytic and antidepressant like activities of the K.parviflora rhizome extract. Aged male Wistar rats were orally administered the alcoholic extract of this plant at various doses ranging from 100, 200 and 300 mg kgˉ1 BW once daily for 7 days. The anxiolytic and antidepressant activities were performed after both single and repetitive treatment for 7 days using elevated plus maze and forced swimming tests respectively. The results showed that the extract decreased immobility time with the increase swimming time. However, no changes in number of open arm entries and time spent in open arm were observed. These results suggested the anti-depression activity of the plant extract. Therefore, K.parviflora may be served as a potential resource for natural psychotherapeutic agent against depression. However, further studies were still required.

  5. Radioactive cDNA microarrys for gene expression profiles in antidepressant therapy

    International Nuclear Information System (INIS)

    Using radioactive cDNA microarray, we investigated a pattern of gene regulation under treatment of antidepressant on patients of depressive disoder. Basic microarray technology was performed as previously described in our research. The bioinformatic selection of human cDNAs, which is specifically designed for psychiatry, neurology, and signal transduction, were arrayed on nylon membranes. Using with 33P-labeled probes, this method provided highly sensitive gene expression profiles of our interest including brain receptors, drug metabolism, and cellular signalings. Gene expression profiles were also classified into several categories in accordance with the gene-regulation of antidepressant. The gene profiles of our interest were significantly up- (16 genes, >2.0 of Z-ratio) or down- (24 genes, <-2.0 of Z ratio) regulated when compared the good responsed group with the bad-responsed one. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology

  6. STUDY OF ANTIDEPRESSANT LIKE EFFECT OF CORIANDRUM SATIVUM AND INVOLVEMENT OF MONOAMINONERGIC AND GABANERGIC SYSTEM

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    Naikwade Nilofer

    2011-02-01

    Full Text Available The aim of this study was to examine possible mechanism of action of aqueous extract of Coriandrum sativum seed central nervous system of mice. We investigated the antidepressant-like mechanism of Coriandrum sativum by the combination of the Sulpiride (a selective dopamine D2 receptor antagonist, Prazosin (a α1 adrenoceptor antagonist, and Baclofen (GABA agonist. The results show that Coriandrum sativum (200 mg/kg, 400mg/kg, p.o., significantly reduced the immobility time during Tail Suspension Test (TST. We also investigated the antidepressant-like mechanism of Coriandrum sativum by the combination of Sulpiride (a selective dopamine D2 receptor antagonist, Prazosin (a α1 adrenoceptor antagonist, and Baclofen (GABA agonist. The immobility time after treatment with Coriandrum sativum (200 mg/kg, 400mg/kg, p.o. in TST was augmented by Sulpiride, Baclofen, Prazosin. Our findings support the view that Coriandrum sativum exerts antidepressant-like effect. And the mechanism of action of Coriandrum sativum may be related to the increase in Nor adrenaline and serotonin levels in the hippocampus and frontal cortex.

  7. Improvement of Glycemic Control in Insulin-Dependent Diabetics with Depression by Concomitant Treatment with Antidepressants.

    Science.gov (United States)

    Radojkovic, Jana; Sikanic, Natasa; Bukumiric, Zoran; Tadic, Marijana; Kostic, Nada; Babic, Rade

    2016-01-01

    BACKGROUND It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. MATERIAL AND METHODS Total of 192 patients with poorly controlled diabetes (defined as HbA1c ≥8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II ≥14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. RESULTS Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.0±1.8% to 8.5±1.2% (pdepression scale and improvement in glycemic control was observed (R²=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. CONCLUSIONS Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status. PMID:27329213

  8. Seasonal Affective Disorder (SAD: Role of lamotrigine augmentation to anti-depressant medication in winter depression

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    Arshad Hussain

    2015-01-01

    Full Text Available Background: Many therapeutic options have been evaluated and tried for seasonal affective disorder (SAD including bright light therapy (BLT, anti-depressants, beta-blockers and psychotherapy, but the data supporting use of mood-stabilizing agents is just handful in spite of this condition being understood most frequently to be associated with bipolar affective disorder II (BPAD II. So we planned to study role of Lamotrigine (Mood stabilizing agent in SAD. Materials and Methods: 30 patients of SAD who were prescribed lamotrigine in addition to antidepressant medications for a minimum of 8 weeks and were assessed for severity using HAM-D were selected retrospectively from the hospital records for this study. HAM-D scores at 2, 4 and 8 weeks were compared to baseline scores. Statistics Analysis: Single tailed t-test was used to study the difference of means to assess the therapeutic response and pre/post analysis of change. Statistical significance was set at P < 0.05. Results: Though no significant difference was seen in HAM-D Scores at 2 weeks of treatment compared to baseline, but results were statistically significant at 4 and 8 weeks of treatment with lamotrigine augmentation of antidepressant medications. Conclusion: We conclude that lamotrigine augmentation was found to be effective treatment strategy for managing winter depression phase of Seasonal Affective Disorder.

  9. Impact of Antidepressants on Cytokine Production of Depressed Patients in Vitro

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    Alexander Munzer

    2013-11-01

    Full Text Available The interplay between immune and nervous systems plays a pivotal role in the pathophysiology of depression. In depressive episodes, patients show increased production of pro-inflammatory cytokines such as interleukin (IL-1β and tumor necrosis factor (TNF-α. There is limited information on the effect of antidepressant drugs on cytokines, most studies report on a limited sample of cytokines and none have reported effects on IL-22. We systematically investigated the effect of three antidepressant drugs, citalopram, escitalopram and mirtazapine, on secretion of cytokines IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in a whole blood assay in vitro, using murine anti-human CD3 monoclonal antibody OKT3, and 5C3 monoclonal antibody against CD40, to stimulate T and B cells respectively. Citalopram increased production of IL-1β, IL-6, TNF-α and IL-22. Mirtazapine increased IL-1β, TNF-α and IL-22. Escitalopram decreased IL-17 levels. The influence of antidepressants on IL-2 and IL-4 levels was not significant for all three drugs. Compared to escitalopram, citalopram led to higher levels of IL-1β, IL-6, IL-17 and IL-22; and mirtazapine to higher levels of IL-1β, IL-17, IL-22 and TNF-α. Mirtazapine and citalopram increased IL-22 production. The differing profile of cytokine production may relate to differences in therapeutic effects, risk of relapse and side effects.

  10. Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression.

    Science.gov (United States)

    Idayu, N Farah; Hidayat, M Taufik; Moklas, M A M; Sharida, F; Raudzah, A R Nurul; Shamima, A R; Apryani, Evhy

    2011-03-15

    Mitragyna speciosa Korth. leaves have been used for decades as a traditional medicine to treat diarrhea, diabetes and to improve blood circulation by natives of Malaysia, Thailand and other regions of Southeast Asia. Mitragynine is the major active alkaloid in the plant. To date, the role of mitragynine in psychological disorders such as depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of mitragynine in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of antidepressant activity and the effect of mitragynine towards neuroendocrine system of hypothalamic-pituitary-adrenal (HPA) axis by measuring the corticosterone concentration of mice exposed to FST and TST. An open-field test (OFT) was used to detect any association of immobility in the FST and TST with changes in motor activity of mice treated with mitragynine. In the present study, mitragynine at dose of 10 mg/kg and 30 mg/kg i.p. injected significantly reduced the immobility time of mice in both FST and TST without any significant effect on locomotor activity in OFT. Moreover, mitragynine significantly reduced the released of corticosterone in mice exposed to FST and TST at dose of 10 mg/kg and 30 mg/kg. Overall, the present study clearly demonstrated that mitragynine exerts an antidepressant effect in animal behavioral model of depression (FST and TST) and the effect appears to be mediated by an interaction with neuroendocrine HPA axis systems. PMID:20869223

  11. Enhanced Antidepressant-Like Effects of Electroacupuncture Combined with Citalopram in a Rat Model of Depression

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    Jian Yang

    2013-01-01

    Full Text Available Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.

  12. Antidepressant effect and pharmacological evaluation of standardized extract of flavonoids from Byrsonima crassifolia.

    Science.gov (United States)

    Herrera-Ruiz, M; Zamilpa, A; González-Cortazar, M; Reyes-Chilpa, R; León, E; García, M P; Tortoriello, J; Huerta-Reyes, M

    2011-11-15

    Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg. PMID:21788126

  13. Radioactive cDNA microarrys for gene expression profiles in antidepressant therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M. S.; Han, B. J.; Cha, J. H.; Ryu, Y. M.; Shin, E. K.; Park, J. H.; Park, Y. H.; Kim, M. K. [Korea University Medical College, Seoul (Korea, Republic of)

    2002-07-01

    Using radioactive cDNA microarray, we investigated a pattern of gene regulation under treatment of antidepressant on patients of depressive disoder. Basic microarray technology was performed as previously described in our research. The bioinformatic selection of human cDNAs, which is specifically designed for psychiatry, neurology, and signal transduction, were arrayed on nylon membranes. Using with 33P-labeled probes, this method provided highly sensitive gene expression profiles of our interest including brain receptors, drug metabolism, and cellular signalings. Gene expression profiles were also classified into several categories in accordance with the gene-regulation of antidepressant. The gene profiles of our interest were significantly up- (16 genes, >2.0 of Z-ratio) or down- (24 genes, <-2.0 of Z ratio) regulated when compared the good responsed group with the bad-responsed one. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology.

  14. Antidepressants detection and quantification in whole blood samples by GC-MS/MS, for forensic purposes.

    Science.gov (United States)

    Truta, Liliana; Castro, André L; Tarelho, Sónia; Costa, Pedro; Sales, M Goreti F; Teixeira, Helena M

    2016-09-01

    Depression is among the most prevalent psychiatric disorders of our society, leading to an increase in antidepressant drug consumption that needs to be accurately determined in whole blood samples in Forensic Toxicology Laboratories. For this purpose, this work presents a new gas chromatography tandem mass spectrometry (GC-MS/MS) method targeting the simultaneous and rapid determination of 14 common Antidepressants in whole blood: 13 Antidepressants (amitriptyline, citalopram, clomipramine, dothiepin, fluoxetine, imipramine, mianserin, mirtazapine, nortryptiline, paroxetine, sertraline, trimipramine and venlafaxine) and 1 Metabolite (N-desmethylclomipramine). Solid-phase extraction was used prior to chromatographic separation. Chromatographic and MS/MS parameters were selected to improve sensitivity, peak resolution and unequivocal identification of the eluted analyte. The detection was performed on a triple quadrupole tandem MS in selected ion monitoring (SIM) mode in tandem, using electronic impact ionization. Clomipramine-D3 and trimipramine-D3 were used as deutered internal standards. The validation parameters included linearity, limits of detection, lower limit of quantification, selectivity/specificity, extraction efficiency, carry-over, precision and robustness, and followed internationally accepted guidelines. Limits of quantification and detection were lower than therapeutic and sub-therapeutic concentration ranges. Overall, the method offered good selectivity, robustness and quick response (<16min) for typical concentration ranges, both for therapeutic and lethal levels. PMID:27376459

  15. The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects.

    Science.gov (United States)

    Kondo, M; Nakamura, Y; Ishida, Y; Shimada, S

    2015-11-01

    Exercise has a variety of beneficial effects on brain structure and function, such as hippocampal neurogenesis, mood and memory. Previous studies have shown that exercise enhances hippocampal neurogenesis, induces antidepressant effects and improves learning behavior. Brain serotonin (5-hydroxytryptamine, 5-HT) levels increase following exercise, and the 5-HT system has been suggested to have an important role in these exercise-induced neuronal effects. However, the precise mechanism remains unclear. In this study, analysis of the 5-HT type 3A receptor subunit-deficient (htr3a(-/-)) mice revealed that lack of the 5-HT type 3 (5-HT3) receptor resulted in loss of exercise-induced hippocampal neurogenesis and antidepressant effects, but not of learning enhancement. Furthermore, stimulation of the 5-HT3 receptor promoted neurogenesis. These findings demonstrate that the 5-HT3 receptor is the critical target of 5-HT action in the brain following exercise, and is indispensable for hippocampal neurogenesis and antidepressant effects induced by exercise. This is the first report of a pivotal 5-HT receptor subtype that has a fundamental role in exercise-induced morphological changes and psychological effects. PMID:25403840

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

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    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.

  17. Antidepressant Suppression of Non-REM Sleep Spindles and REM Sleep Impairs Hippocampus-Dependent Learning While Augmenting Striatum-Dependent Learning

    OpenAIRE

    Watts, Alain; Gritton, Howard J.; Sweigart, Jamie; Poe, Gina R.

    2012-01-01

    Rapid eye movement (REM) sleep enhances hippocampus-dependent associative memory, but REM deprivation has little impact on striatum-dependent procedural learning. Antidepressant medications are known to inhibit REM sleep, but it is not well understood if antidepressant treatments impact learning and memory. We explored antidepressant REM suppression effects on learning by training animals daily on a spatial task under familiar and novel conditions, followed by training on a procedural memory ...

  18. Prevalence and Prescription of Antidepressants in Depression with Somatic Comorbidity in Asia: The Research on East Asian Psychotropic Prescription Patterns Study

    OpenAIRE

    Chao Chen; Tian-Mei Si; Yu-Tao Xiang; Ungvari, Gabor S; Chuan-Yue Wang; Yan-Ling He; Ee-Heok Kua; Senta Fujii; Kang Sim; Trivedi, Jitendra K.; Eun-Kee Chung; Pichet Udomratn; Kok-Yoon Chee; Norman Sartorius; Chay-Hoon Tan

    2015-01-01

    Background: Depression is often comorbid with chronic somatic diseases. Few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in Asia. This study aimed to investigate the prevalence of somatic comorbidity (SC) in depression and compared the prescriptions of antidepressants in depressed patients with and without SC. Methods: A total of 2320 patients treated with antidepressants...

  19. Increased neuroplasticity and hippocampal microglia activation in a mice model of rapid antidepressant treatment.

    Science.gov (United States)

    Muzio, Luca; Brambilla, Valentina; Calcaterra, Lorenza; D'Adamo, Patrizia; Martino, Gianvito; Benedetti, Francesco

    2016-09-15

    The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects. Unbiased evaluation of the transcriptional responses were obtained in the hippocampus by Illumina Bead Chip Array system, then confirmed with real time PCR. Spine densities in granular neurons of the dentate gyrus (DG) were assayed by standard Golgi staining. Activation of Microglial/Macrophages cells was evaluated by immunufluorescence analysis for Iba1. Rates of cell proliferation was estimated pulsing mice with the S-phase tracer 5-Iodo-2'-deoxyuridine (IdU). All SD procedures caused a decreasing of floating time at FST, and increased expression of the immediate early gene Arc/Arg3.1. In addition, SSW also increased expression of the Microglia/Macrophages genes Iba-1 and chemokine receptors Cx3cR1 and CxcR4, of the canonical Wnt signaling gene Wnt7a, and of dendritic spines in CA4 neurons of the DG. SSW up-regulated both the number of Iba1+ cells and rates of cell proliferation in the subgranular region of the DG. The antidepressant-like effects of SD dissociated both, from hippocampal neuroplasticity in the DG (not occurring after ASD), and from microglial activation (not preventing behavioral response when occurring). The increase in dendritic spine density in the DG after SD and exercise was associated with an up-regulation of Wnt 7a, and with activation of the innate immune system of the brain. Increased Arc/Arg3.1 suggests however increased neuroplasticity, which could be common to all fast-acting antidepressants

  20. Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants

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    Preeta Kaur Chugh

    2013-01-01

    Full Text Available Background & objectives: Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats. Methods: Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Results: Pretreatment of rats with venlafaxine (40 mg/kg resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01. Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05. Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05 and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05 on day 7. No significant difference with regard to gastric tolerability was observed among groups. Interpretation & conclusions: Our findings showed significant anti

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

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    Schobben Fred

    2009-07-01

    Full Text Available Abstract 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 pregnancy is still a subject of debate. Physicians and pharmacists may have opposing views on using medication during pregnancy and may give contradictory advice on whether or not to take medication for depression and anxiety disorders during pregnancy. In this study, we investigated information sources used by general practitioners (GPs and pharmacists and their common practices. Methods A questionnaire on the use of information sources and the general approach when managing depression during pregnancy was sent out to 1400 health care professionals to assess information sources on drug safety during pregnancy and also the factors that influence decision-making. The questionnaires consisted predominantly of closed multiple-choice questions. Results A total of 130 GPs (19% and 144 pharmacists (21% responded. The most popular source of information on the safety of drug use during pregnancy is the Dutch National Health Insurance System Formulary, while a minority of respondents contacts the Dutch national Teratology Information Service (TIS. The majority of GPs contact the pharmacy with questions concerning drug use during pregnancy. There is no clear line with regard to treatment or consensus between GPs on the best therapeutic strategy, nor do practitioners agree upon the drug of first choice. GPs have different views on stopping or continuing antidepressants during pregnancy or applying alternative treatment options. The debate appears to be ongoing as to whether or not specialised care for mother and child is indicated in cases of gestational antidepressant use. Conclusion Primary health care workers are not univocal concerning therapy for

  2. Prescribing patterns of medicine classified as 'antidepressants' in South African children and adolescents

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    Jan H. P. Serfontein

    2009-04-01

    Full Text Available

    The main objective of this study was to characterise prescribing patterns of medicine classified as 'antidepressants' (hereafter simply referred to as antidepressants in children and adolescents in the private health care sector of South Africa. A retrospective drug utilisation design was used to identify patients aged 19 years and younger from a South African pharmaceutical benefit management company’s database, whom were issued at least one antidepressant between 1 January 2006 and 31 December 2006. Prescribed daily dosages (PDDs were calculated using the Statistical Analysis System® program. A total of 1 013 patients received a mean number of 2.88 (SD 3.04 prescriptions per patient. Females received more prescriptions than their male counterparts, with the highest prevalence in the 15 ≤ 19 years age group. The pharmacological groups most prescribed were the selective serotonin reuptake inhibitors (43.0% and the tricyclics (42.7%, with imipramine (22.04% and amitriptyline (19% as the most commonly prescribed drugs. Approximately 30% (n = 2 300 of all antidepressants in the study population were prescribed off-label. Amitriptyline and clomipramine were prescribed at daily dosages higher than recommended in children and adolescents aged 9 ≤ 15 years. Lithium, trimipramine, trazodone and sulpiride were prescribed at sub-therapeutic dosages in adolescents. This study provided insight in the prescribing patterns of medicine classified as antidepressants in South African children and adolescents. These drugs, however, have many indications. Further research is needed to determine reasons why specific drugs are prescribed in this population.

    Opsomming

    Die algemene doelstelling van hierdie studie was om die voorskrifpatrone van middels wat as 'antidepressante' geklassifiseer word (hierna verwys na as slegs antidepressante wat vir kinders en adolessente in die Suid-Afrikaanse private gesondheidsorgsektor

  3. Risco de câncer associado ao uso de antidepressivos Risk of cancer associated with the use of antidepressants

    Directory of Open Access Journals (Sweden)

    Camila Silva Bôaventura

    2007-04-01

    Full Text Available INTRODUÇÃO: Alguns estudos sugerem que o uso de antidepressivos poderia aumentar o risco de câncer. Este estudo visa realizar uma revisão sobre o tema. MÉTODO: Foi feita uma busca nas bases de dados MEDLINE e LILACS, utilizando como palavras de busca antidepressant, cancer e nomes das diferentes drogas antidepressivas. RESULTADOS: Onze artigos foram selecionados. Foram encontrados seis artigos sugerindo uma associação positiva fraca entre o uso de antidepressivos e o crescimento tumoral e cinco artigos que não sugeriam a associação. Discussão: Os resultados dos estudos com relação ao risco de câncer associado ao uso de antidepressivos são ainda conflitantes. Na maioria dos estudos, a análise multivariada não mostra associação positiva em uso de antidepressivos e câncer, a não ser em casos específicos, como linfoma de Hodgkin.INTRODUCTION: Some studies suggest that the use of antidepressants could increase the risk of cancer. This study aims at performing a review on this subject. METHOD: A search was performed in the MEDLINE and LILACS databases using the keywords antidepressant, cancer and names of varied antidepressant drugs. RESULTS: Eleven articles were selected. Six articles were found suggesting a positive weak association between use of antidepressants and tumoral growth. In five articles this association was not found. DISCUSSION: The results of studies on increased risk of cancer associated with antidepressants are still conflicting. In most studies the multivariate analysis did not show positive association between use of antidepressants and cancer, unless in specific cases, such as Hodgkin's lymphoma.

  4. Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders.

    Science.gov (United States)

    Gupta, Saurabh; Gersing, Kenneth Ronald; Erkanli, Alaattin; Burt, Tal

    2016-06-01

    In 2004 the Food and Drug Administration issued a warning on the risk of suicidality in children and adolescents receiving antidepressants. This was followed by reports of changes in antidepressant prescription patterns, suicidality and other aggressive behaviors, but debate is continuing regarding the nature and magnitude of these changes. We examined a large physician database for impact of the warning on antidepressant prescriptions, suicidality and other aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in adult and pediatric patients. We analyzed electronic database covering over 100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning periods. We compared strength of the association between the measures and the time period with two tests. Multivariate logistic regression analyses were performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0 %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant prescription and 16.1 % were pediatric patients. In post-warning period, there was a greater reduction in adult versus pediatric antidepressant prescription rates. Logistic modeling showed greater likelihood of antidepressant prescription in MDD as compared with anxiety disorders in post-warning period. Pediatric patients were more likely than adults to receive fluoxetine during the post-warning period. There was an overall reduction in suicidality and other aggressive behaviors in the post-warning period. Regulatory warnings may have had an impact on antidepressant benefit/risk assessment and consequent utilization, therapeutic effects, and adverse events. Our observations suggest that psychiatrists may heed regulatory warnings, but may also exert professional independence and discrimination in their application. PMID:26303613

  5. HBK-7 - A new xanthone derivative and a 5-HT1A receptor antagonist with antidepressant-like properties.

    Science.gov (United States)

    Pytka, Karolina; Kazek, Grzegorz; Siwek, Agata; Mordyl, Barbara; Głuch-Lutwin, Monika; Rapacz, Anna; Olczyk, Adrian; Gałuszka, Adam; Waszkielewicz, Anna; Marona, Henryk; Sapa, Jacek; Filipek, Barbara; Zygmunt, Małgorzata

    2016-01-01

    Xanthone derivatives possess many biological properties, including neuroprotective, antioxidant or antidepressant-like. In this study we aimed to investigate antidepressant- and anxiolytic-like properties of a new xanthone derivative - 6-methoxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]-9H-xanthen-9-one (HBK-7), as well as its possible mechanism of action, and the influence on cognitive and motor function. HBK-7 in our earlier studies showed high affinity for serotonergic 5-HT1A receptor. We determined the affinity of HBK-7 for CNS receptors and transporters using radioligand assays and examined its intrinsic activity towards 5-HT1A receptor. We evaluated antidepressant- and anxiolytic-like activity of HBK-7 in the mouse forced swim test, and four-plate test, respectively. We examined the influence on locomotor activity in mice to determine if the effect observed in the forced swim test was specific. We used step-through passive avoidance and rotarod tests to evaluate the influence of HBK-7 on cognitive and motor function, respectively. HBK-7 showed moderate affinity for dopaminergic D2 receptor and very low for serotonergic 5-HT2A, adrenergic α2 receptors, as well as serotonin transporter. Functional studies revealed that HBK-7 was a 5-HT1A receptor antagonist. HBK-7 (10mg/kg) decreased immobility time in the forced swim test. Combined treatment with sub-effective doses of HBK-7 and fluoxetine reduced immobility of mice in the forced swim test. Pretreatment with p-chlorophenylalanine and WAY-100,635 antagonized the antidepressant-like effect of HBK-7. Neither of the treatments influenced locomotor activity of mice. HBK-7 at antidepressant-like dose did not impair memory or motor coordination in mice. We demonstrated that HBK-7 was a 5-HT1A receptor antagonist with potent, comparable to mianserin, antidepressant-like activity. HBK-7 mediated its effect through serotonergic system and its antidepressant-like action required the activation of 5-HT1A receptors. At active

  6. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.

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    Jean Mazella

    Full Text Available Current antidepressant treatments are inadequate for many individuals, and when they are effective, they require several weeks of administration before a therapeutic effect can be observed. Improving the treatment of depression is challenging. 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. In mice, deletion of the TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate in mice the antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the neurotensin receptor 3 (NTSR3/Sortilin and acting through TREK-1 inhibition. NTSR3/Sortilin interacted with the TREK-1 channel, as shown by immunoprecipitation of TREK-1 and NTSR3/Sortilin from COS-7 cells and cortical neurons co-expressing both proteins. TREK-1 and NTSR3/Sortilin were colocalized in mouse cortical neurons. Spadin bound specifically to TREK-1 with an affinity of 10 nM. Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices. Spadin also induced in vivo an increase of the 5-HT neuron firing rate in the Dorsal Raphe Nucleus. In five behavioral tests predicting an antidepressant response, spadin-treated mice showed a resistance to depression as found in TREK-1 deficient mice. More importantly, an intravenous 4-d treatment with spadin not only induced a strong antidepressant effect but also enhanced hippocampal phosphorylation of CREB protein and neurogenesis, considered to be key markers of antidepressant action after chronic treatment with selective serotonin reuptake inhibitors. This work also shows the development of a reliable method for dosing the propeptide in serum of mice by using AlphaScreen technology. These findings point out

  7. Enzymatic Depletion of the Polysialic Acid Moiety Associated with the Neural Cell Adhesion Molecule Inhibits Antidepressant Efficacy.

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    Wainwright, Steven R; Barha, Cindy K; Hamson, Dwayne K; Epp, Jonathan R; Chow, Carmen; Lieblich, Stephanie E; Rutishauser, Urs; Galea, Liisa Am

    2016-05-01

    Antidepressant drugs are too often ineffective, the exact mechanism of efficacy is still ambiguous, and there has been a paucity of novel targets for pharmacotherapy. In an attempt to understand the pathogenesis of depression and subsequently develop more efficacious antidepressant drugs, multiple theories have been proposed, including the modulation of neurotransmission, the upregulation of neurogenesis and neurotrophic factors, normalizing hypothalamic-pituitary-adrenal reactivity, and the reduction of neuroinflammation; all of which have supporting lines of evidence. Therefore, an ideal molecular target for novel pharmaceutical intervention would function at the confluence of these theories. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) functions broadly, serving to mediate synaptic plasticity, neurogenesis, neurotrophic factor signaling, and inflammatory signaling throughout the brain; all of which are associated with the pathophysiology and treatment of depression. Moreover, the expression of PSA-NCAM is reduced by depression, and conversely enhanced by antidepressant treatment, particularly within the hippocampus. Here we demonstrate that selectively cleaving the polysialic acid moiety, using the bacteriophage-derived enzyme endoneuraminidase N, completely inhibits the antidepressant efficacy of the selective-serotonin reuptake inhibitor fluoxetine (FLX) in a chronic unpredictable stress model of depression. We also observe a corresponding attenuation of FLX-induced hippocampal neuroplasticity, including decreased hippocampal neurogenesis, synaptic density, and neural activation. These data indicate that PSA-NCAM-mediated neuroplasticity is necessary for antidepressant action; therefore PSA-NCAM represents an interesting, and novel, target for pharmacotherapy. PMID:26530284

  8. Regulation of proteolytic cleavage of brain-derived neurotrophic factor precursor by antidepressants in human neuroblastoma cells

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    Lin PY

    2015-10-01

    Full Text Available Pao-Yen Lin1,2 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 2Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Abstract: Evidence has supported the role of brain-derived neurotrophic factor (BDNF in antidepressant effect. The precursor of BDNF (proBDNF often exerts opposing biological effects on mature BDNF (mBDNF. Hence, the balance between proBDNF and mBDNF might be critical in total neurotrophic effects, leading to susceptibility to or recovery from depression. In the current study, we measured the protein expression levels of proBDNF, and its proteolytic products, truncated BDNF, and mBDNF, in human SH-SY5Y cells treated with different antidepressants. We found that the treatment significantly increased the production of mBDNF, but decreased the production of truncated BDNF and proBDNF. These results support that antidepressants can promote proBDNF cleavage. Further studies are needed to clarify whether proBDNF cleavage plays a role in antidepressant mechanisms. Keywords: antidepressant, mature BDNF, neurotrophic effect, proBDNF cleavage 

  9. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF

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    Hurley, Laura L.; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol; Tizabi, Yousef

    2012-01-01

    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant effects of many drugs, we also evaluated the effects of curcumin on BDNF in the hippocampus. Adult male Wistar Kyoto (WKY) rats, a putative model of depression, were injected acutely or chronically (10 d) with 50, 100, and 200mg/kg curcumin. Open field locomotor activity (OFLA) and forced swim test (FST), a measure of helplessness, were measured 1 hour after acute and 18–20 hours after last chronic injection. Results showed a dose-dependent reduction of immobility in the FST by curcumin in both acute and chronic studies, without any significant effect on OFLA. The effect of higher chronic curcumin dose in FST was still evident a week later. Chronic curcumin also resulted in a dose-dependent increase in hippocampal BDNF. This data provides evidence for an antidepressant-like effect of curcumin, possibly through increased neurotrophic activity, in the WKY model of depression, and support the notion that curcumin may prove an effective and lasting natural antidepressant. PMID:23142609

  10. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

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    Bahareh Amin

    2015-08-01

    Full Text Available Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p. were evaluated using forced swim test (FST. In sub-acute study (21 times with 24-h intervals, antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST. Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg and crocetin (20 and 40 mg/kg produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg. Crocetin (12.5, 25 and 50 mg/kg was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.

  11. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

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    Go Taniguchi

    2015-01-01

    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. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each, impaired consciousness appeared. Electroencephalography (EEG showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

  12. The antidepressant- and anxiolytic-like activities of new xanthone derivative with piperazine moiety in behavioral tests in mice

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    Pytka, Karolina; Żmudzka, Elżbieta; Lustyk, Klaudia; Rapacz, Anna; Olczyk, Adrian; Gałuszka, Adam; Waszkielewicz, Anna; Marona, Henryk; Sapa, Jacek; Barbara, Filipek

    2016-01-01

    Objectives: Xanthones are flavonoids with numerous activities, including antioxidant, antidepressant., or anxiolytic-like. Therefore, the aim of our study was to determine antidepressant- and anxiolytic-like properties of four xanthone derivatives (3-chloro-5-[(4-methylpiperazin-1-yl)methyl]-9H-xanthen-9-one dihydrochloride [HBK-5], 6-methoxy-2-[(4-methylpiperazin-1-yl) methyl]-9H-xanthen-9-one dihydrochloride, 2-[(4-benzylpiperazin-1-yl) methyl]-6-methoxy-9H-xanthen-9-one dihydrochloride, 2-{[4-(2-methoxyphenyl) piperazin-1-yl] methyl}-9H-xanthen-9-one hydrochloride), as well as the influence on cognitive and motor function of active compounds, using animal models. Materials and Methods: To determine the antidepressant-like activity, we used forced swim test (FST) and tail suspension test (TST) in mice. We evaluated anxiolytic-like properties in the four-plate test in mice. We studied the influence on cognitive and motor function in passive avoidance step-through and chimney tests, respectively. Results: The antidepressant-like activity (in both FST and TST) showed only HBK-5. Moreover, the compound was also active in the four-plate test, which suggests that it possessed anxiolytic-like properties. HBK-5 did not cause any cognitive and motor deficits in mice at antidepressant- and anxiolytic-like doses. Conclusions: HBK-5 may have potential in the treatment of depression or anxiety disorders, but this issue needs further studies. PMID:27298499

  13. Putative role of monoamines in the antidepressant-like mechanism induced by striatal MT2 blockade.

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    Noseda, Ana Carolina D; Rodrigues, Lais S; Targa, Adriano D S; Aurich, Mariana F; Vital, Maria A B F; Da Cunha, Cláudio; Lima, Marcelo M S

    2014-12-15

    It has been observed that the secretion pattern of melatonin is modified in Parkinson's disease (PD). Hence, it is hypothesized that dysregulations of melatonin MT2 receptors may be involved in the installation of depression in PD patients. Together with recent evidence based on the use of the intranigral rotenone model of PD, have led to the hypothesis that modulating the striatal MT2 receptor could provide a more comprehensive understanding of the antidepressant properties triggered. To further investigate this issue, male Wistar rats were infused with intranigral rotenone (12μg/μL) and seven days later subjected to a rapid eye movement sleep deprivation (REMSD) for 24h. After, we injected within the striatum the MT2 selective agonist, 8-M-PDOT (10μg/μL), the MT2 selective antagonist, 4-P-PDOT (5μg/μL) or vehicle. Subsequently, they were tested in the forced swimming test and were allowed to perform the sleep rebound (REB). Then, the rats were re-tested, and the striatum, hippocampus and substantia nigra pars compacta (SNpc) were collected for neurochemical purposes. Results indicated substantial antidepressant effects promoted by the blockade of striatal MT2 receptors that were potentiated by REMSD. MT2 activation increased DA levels in the striatum and hippocampus, while MT2 blockade increase DA in the SNpc. 4-P-PDOT treatment of the rotenone REMSD group generated a decrement in 5-HT levels within the striatum, hippocampus and SNpc. However, increased 5-HT turnover was observed among these structures. Therefore, we demonstrated the neurochemical antidepressant effect induced by striatal MT2 blockage associated with REMSD in the rotenone model of PD. PMID:25218873

  14. Use of antidepressants in the treatment of depression in Asia: guidelines, clinical evidence, and experience revisited.

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    Treuer, Tamás; Liu, Chia-Yih; Salazar, Gerardo; Kongsakon, Ronnachai; Jia, Fujun; Habil, Hussain; Lee, Min-Soo; Lowry, Amanda; Dueñas, Héctor

    2013-12-01

    Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients. PMID:23857712

  15. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

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    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials. PMID:26650973

  16. Sociodemographic and clinical predictors of compliance with antidepressants for depressive disorders: systematic review of observational studies

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    Rivero-Santana A

    2013-03-01

    Full Text Available Amado Rivero-Santana,1 Lilisbeth Perestelo-Perez,2,3 Jeanette Pérez-Ramos,1 Pedro Serrano-Aguilar,2,3 Carlos De las Cuevas2,4 1Canary Islands Foundation of Health and Research, 2Red de Investigacion en Servicios de Salud en Enfermedades Cronicas (REDISSEC, Santa Cruz de Tenerife, 3Evaluation Unit, Canary Islands Health Service, Santa Cruz de Tenerife, 4Department of Psychiatry, University of La Laguna, Canary Islands, Spain Background: The literature shows that compliance with antidepressant treatment is unsatisfactory. Several personal and disease-related variables have been shown to be related to compliance behavior. The objective of this study was to review the literature about sociodemographic and clinical predictors of compliance in patients with depressive disorders. Methods: The Medline, Embase, Cochrane Central, PsycInfo, and Cinahl databases were searched until May 2012. Studies that analyzed sociodemographic and clinical predictors or correlates of compliance in patients with depressive disorder were included. A quantitative synthesis was not performed because of the heterogeneity and availability of the data reported. For similar reasons, the results were not classified according to the different phases of treatment. The search was limited to studies published in English and Spanish. Results: Thirty-two studies fulfilled the inclusion criteria. The most consistent associations with compliance were found for age (older patients showed more compliance and race (white patients were more likely to adhere to treatment than minority ethnic groups. Few studies assessed clinical factors, and the most plausible predictors of compliance were certain comorbidities and substance abuse. Severity of depression did not play an important role in predicting compliance. Conclusion: The impact of the variables studied on compliance behavior appeared to be inconsistent. Identifying potential predictors of compliance with antidepressant treatment is

  17. Information on antidepressants for psychiatric inpatients: the divide between patient needs and professional practice

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    Desplenter FA

    2013-06-01

    Full Text Available Background: Medicine information is an integral part of patient care and a patient right. In particular, patients with a mental health diagnosis have a need for information on medicines. Objective: This study aims to describe the current practice on information provision on antidepressants to inpatients in psychiatric hospitals.Methods: A qualitative study was conducted consisting of semi-structured interviews with health care professionals (n=46 and patients (n=17 in 11 Flemish psychiatric hospitals. Two topic guides were designed for conducting the interviews with these respective stakeholders. The issues addressed in the topic guides related to: organization of information provision in the hospital, information on demand of the patient, information provision by health care professionals, information for relatives, evaluation of provided information, interdisciplinary contacts on information provision and satisfaction on current practice of information provision. The interviews were analysed according to the five stages of the framework analysis.Results: Psychiatrists and nurses are the key players to provide information on antidepressants. Their approach depends on patient characteristics and mental state. Information is provided mainly orally. Health care professionals consider non-verbal cues of patients to verify if information has been understood. Health care professionals reported lack of time and lack of interdisciplinary contacts as negative aspects. Patients indicated that health care professionals take too little initiative to provide medicine information. Conclusions: Patients are informed about their antidepressants through various pathways. Although the awareness is present of the importance of the individual approach and efforts are done to tailor information to the individual patient, improvement is still possible. Tailoring communication; assessing patient needs and preferences; matching of health care professional style and

  18. A translational rodent assay of affective biases in depression and antidepressant therapy.

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    Stuart, Sarah A; Butler, Paul; Munafò, Marcus R; Nutt, David J; Robinson, Emma Sj

    2013-08-01

    The subjective measures used to study mood disorders in humans cannot be replicated in animals; however, the increasing application of objective neuropsychological methods provides opportunities to develop translational animal tasks. Here we describe a novel behavioral approach, which has enabled us to investigate similar affective biases in rodents. In our affective bias test (ABT), rats encounter two independent positive experiences--the association between food reward and specific digging substrate--during discrimination learning sessions. These are performed on separate days under either neutral conditions or during a pharmacological or affective state manipulation. Affective bias is then quantified using a preference test where both previously rewarded substrates are presented together and the rat's choices recorded. The absolute value of the experience is kept consistent and all other factors are counterbalanced so that any bias at recall can be attributed to treatment. Replicating previous findings from studies in healthy volunteers, we observe significant positive affective biases following acute treatment with typical (fluoxetine, citalopram, reboxetine, venlafaxine, clomipramine) and atypical antidepressants (agomelatine, mirtazapine), and significant negative affective biases following treatment with drugs associated with inducing negative affective states in humans (FG7142, rimonabant, 13-cis retinoic acid). We also observed that acute psychosocial stress and environmental enrichment induce significant negative and positive affective biases, respectively, and provide evidence that these affective biases involve memory consolidation. The positive and negative affective biases induced in our test also mirror the antidepressant and pro-depressant effects of these drugs in patients suggesting our test has both translational and predictive validity. Our results suggest that cognitive affective biases could contribute to drug- or stress-induced mood changes

  19. Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands

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    Zdzisław Chilmonczyk

    2015-08-01

    Full Text Available Serotonin (5-HT is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems, which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies.

  20. Beneficial effect of antidepressants against rotenone induced Parkinsonism like symptoms in rats.

    Science.gov (United States)

    Sharma, Nidhika; Jamwal, Sumit; Kumar, Puneet

    2016-06-01

    Parkinson's disease is a second most common age-related neurodegenerative disorder characterized by the loss of DA neurons of SNpc region of the midbrain. Neurotransmitter dysfunction is involved in the pathogenesis of PD. Antidepressants like venlafaxine and sertraline expected to improve Parkinsonism like symptoms by modulating the levels of various neurotransmitters. The neuroprotective role of antidepressants is well explored in various CNS disorders. Therefore, this study was designed to explore and compare the mechanistic role of different antidepressants (venlafaxine and sertraline) against rotenone induced Parkinsonism like symptoms in rats. Rats were administrated with rotenone (1.5mg/kg/day; s.c.) daily for a period of 28 days. Venlafaxine (10 and 20mg/kg; p.o.), sertraline (10 and 20mg/kg; p.o.) and Levodopa combination with Carbidopa (10mg/kg; p.o.) were administered daily starting from 7th day one hour prior to rotenone administration. Behavioral parameters (body weight, rotarod, grip strength, narrow beam walk and open field) were assessed on weekly basis. On 28th day, animals were sacrificed and striatum were isolated for biochemical (LPO, GSH and nitrite), neuroinflammatory (TNF-α, IL-1β and IL-6), neurochemical (DA, NE, 5-HT, GABA, Glutamate, DOPAC, HVA and 5-HIAA) and mitochondrial complex-I estimation. Rotenone administration significantly reduced body weight, motor coordination, oxidative defense, increased pro-inflammatory mediators and decreased level of catecholamines. Pre-treatment with venlafaxine and sertraline significantly attenuated the alteration in behavioral, oxidative stress, neuroinflammatory, mitochondrial and catecholamines level in striatum. The study provides a hope that these drugs could be used as adjuvant therapy in the management and treatment of PD. PMID:26996500