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Sample records for including tricyclic antidepressants

  1. Tricyclic Antidepressants and Tetracyclic Antidepressants

    Science.gov (United States)

    Diseases and Conditions Depression (major depressive disorder) Tricyclic and tetracyclic antidepressants affect brain chemicals to ease depression symptoms. Explore their possible side effects and whether one of these antidepressants may be a good option for you. By Mayo Clinic ...

  2. Linking tricyclic antidepressants to ionotropic glutamate receptors.

    Science.gov (United States)

    Stoll, Laura; Gentile, Lisa

    2005-07-29

    Although tricyclic antidepressants have been in existence since the 1940s when they were discovered upon screening iminodibenzyl derivatives for other potential therapeutic uses, their mechanism of action has remained unclear [A. Goodman Gilman, T.W. Rall, A.S. Nies, P. Taylor, Goodman and Gilman's The Pharmacological Basis of Therapeutics, eighth ed., Pergamon Press, New York, 1990]. In addition to their ability to hinder the reuptake of biogenic amines, there is mounting evidence that the tricyclic antidepressants inhibit glutamate transmission. Here, intrinsic tryptophan fluorescence spectroscopy is used to document the binding of desipramine, a member of the tricyclic antidepressant family, to a well-defined extracellular glutamate binding domain (S1S2) of the GluR2 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. The binding is distinct from those of other known effectors of the receptor, including the endogenous sulfated neurosteroids pregnenolone sulfate and 3alpha-hydroxy-5beta-pregnan-20-one sulfate, and is consistent with a conformational change upon binding that is allosterically transmitted to the channel region of the receptor.

  3. 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...... methodology, the subgroup responsible for this poison reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND...... yielding a very low quality of evidence for all recommendations. Data on 108 patients, including 12 fatalities, were abstracted. The workgroup concluded that TCAs are not dialyzable and made the following recommendation: ECTR is not recommended in severe TCA poisoning (1D). The workgroup considers...

  4. Poisoining with Tricyclic Antidepressants and Current Treatment

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    Muge Gulen

    2016-12-01

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

  5. Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons.

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    Beckmann, Nadine; Sharma, Deepa; Gulbins, Erich; Becker, Katrin Anne; Edelmann, Bärbel

    2014-01-01

    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.

  6. Inhibition of acetylcholinesterase from Electrophorus electricus (L.) by tricyclic antidepressants.

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    Nunes-Tavares, N; Nery da Matta, A; Batista e Silva, C M; Araújo, G M N; Louro, S R W; Hassón-Voloch, A

    2002-09-01

    The effects of tricyclic antidepressants drugs (TCA) amitriptyline, imipramine and nortriptyline, on purified Electrophorus electricus (L.) acetylcholinesterase (AChE; acetylcholine hydrolase, EC 3.1.1.7) were studied using kinetic methods and specific fluorescent probe propidium. The antidepressants inhibited AChE activity by a non-competitive mechanism. Inhibition constants range from 200 to 400 microM. Dimethylated amitriptyline and imipramine were more potent inhibitors than the monomethylated nortriptyline. Fluorescence measurements using bis-quaternary ligand propidium were used to monitor ligand-binding properties of these cationic antidepressants to the AChE peripheral anionic site (PAS). This ligand exhibited an eight-fold fluorescence enhancement upon binding to the peripheral anionic site of AChE from E. electricus (L.) with K(D)=7 x 10(-7)M. It was observed that TCA drugs displaced propidium from the enzyme. On the basis of the displacement experiments antidepressant dissociation constants were determined. Similar values for the inhibition constants suggest that these drugs have similar affinity to the peripheral anionic site. The results also indicate that the catalytic active center of AChE does not participate in the interaction of enzyme with tricyclic antidepressants. These studies suggest that the binding site for tricyclic antidepressants is located at the peripheral anionic site of E. electricus (L.) acetylcholinesterase.

  7. Pharmacokinetic study of yohimbine and its pharmacodynamic effects on salivary secretion in patients treated with tricyclic antidepressants.

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    Bagheri, H; Picault, P; Schmitt, L; Houin, G; Berlan, M; Montastruc, J L

    1994-01-01

    The pharmacokinetic parameters and the time course of the effect after acute oral administration of yohimbine on salivary secretion in patients treated with tricyclic antidepressants were investigated. Yohimbine (10 mg) increased both salivary outflow and plasma noradrenaline levels for 4 h. Pharmacokinetic parameters (t1/2, tmax, Cmax and AUCexp) and plasma concentrations of noradrenaline were higher in patients treated with tricyclic antidepressants than in controls. At this dose, yohimbine induced a relatively large number of side effects. A lower dose (4 mg) increased salivary secretion for 3 h without any side effects in patients treated with tricyclic antidepressants but not in healthy volunteers. These data describe an interaction between yohimbine and tricyclic antidepressants and thus show that a relatively low dose (4 mg) of yohimbine could be useful in the treatment of dry mouth due to tricyclic antidepressants. PMID:8148228

  8. MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression.

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    Kostowski, W; Danysz, W; Dyr, W; Jankowska, E; Krzaścik, P; Pałejko, W; Stefański, R; Płaźnik, A

    1991-01-01

    In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.

  9. Tricyclic antidepressants: effects on extinction and fear learning.

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    Ellison, G; Handel, J; Rogers, R; Weiss, J

    1975-01-01

    Rats trained to run an alley for a food reward were extinguished following injections of different antidepressants. When retested several days later, the animals extinguished following pretreatment with the NE reuptake blocker protriptyline showed faster running speeds than did the other groups. Other rats given electrical shocks following pretreatment with protriptyline avoided the compartment in which they had been shocked less than did animals shocked following pretreatment with other antidepressants. This implies an interferance with some aspect of the learning or consolidation process which is correlated with the degree of NE reuptake blockage. It is hypothesized that NE terminals are deactivated following frustrative nonreward or punishment by the conversion and reuptake of the released NE to an altered extinction molecule.

  10. Efficacy of tricyclic antidepressants in irritable bowel syndrome: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Roja Rahimi; Shekoufeh Nikfar; Ali Rezaie; Mohammad Abdollahi

    2009-01-01

    We aimed to evaluate the efficacy of tricyclic antidepressants (TCAs) as a therapeutic option for irritable bowel syndrome (IBS) through meta-analysis of randomized controlled trials. For the years 1966 until September 2008, PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for double-blind, placebo-controlled trials investigating the efficacy of TCAs in the management of IBS. Seven randomized, placebo-controlled clinical trials met our criteria and were included in the metaanalysis. TCAs used in the treatment arm of these trials included amitriptyline, imipramine, desipramine, doxepin and trimipramine. The pooled relative risk for clinical improvement with TCA therapy was 1.93 (95% CI: 1.44 to 2.6, P<0.0001). Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15 (95% CI: -53.27 to -35.04, P<0.0001). It is concluded that low dose TCAs exhibit clinically and statistically significant control of IBS symptoms.

  11. Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants – a case series

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    Kirino E

    2011-12-01

    Full Text Available Eiji Kirino, Masao GitohDepartment of Psychiatry, Juntendo University, School of Medicine, Shizuoka, JapanAbstract: Suicide is a serious social problem in many countries, including Japan. The majority of people who commit suicide suffer from depression. Suicide attempt patients suffering from serious physical injuries are initially treated in hospital emergency departments. The present post hoc analysis examined data from patients admitted to an emergency hospital for treatment of physical injuries, resulting from a suicide attempt, and initial psychiatric treatment for depression and prevention of future suicide attempts. The effects on depressive symptoms were studied in two groups of patients using the 17-item Hamilton depression scale (HAMD. One group (n = 6 had received intravenous tricyclic antidepressants (TCA (amitriptyline or clomipramine while the other group (n = 7 had been treated orally with milnacipran, a serotonin and norepinephrine reuptake inhibitor antidepressant. Prior to treatment the four highest scoring items on the HAMD scale were the same in both groups namely, item 1 (depressed mood, item 3 (suicidality, item 7 (interest in work and activities, and item 10 (psychic anxiety. After 1 week of treatment, mean global HAMD scores were significantly reduced in both groups. Treatment resulted in a significant reduction of five HAMD items in the TCA group, whereas in the milnacipran group 12 HAMD items were significantly reduced. Suicidality (item 3 was significantly improved by 1 week treatment with milnacipran, but not by TCAs. Milnacipran rapidly improved a wide range of depressive symptoms, including suicidality within the first week. The improvement with milnacipran would appear to be, at least, equivalent to that achieved with TCAs, possibly affecting a wider range of symptoms. Since milnacipran has been shown in comparative studies to be better tolerated than TCAs, this antidepressant offers an interesting option for the

  12. Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

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    Antunes, Michelle S; Ruff, Jossana Rodrigues; de Oliveira Espinosa, Dieniffer; Piegas, Manuela Bastos; de Brito, Maicon Lenon Otenio; Rocha, Kellen Athaíde; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Donato, Franciele; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

  13. Tricyclic Antidepressants Found in Pilots Fatally Injured in Civil Aviation Accidents.

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    Dulkadir, Zeki; Chaturvedi, Arvind K; Craft, Kristi J; Hickerson, Jeffery S; Cliburn, Kacey D

    2017-01-01

    Prevalence of tricyclic antidepressants (TCAs) has not been explored in pilots. The National Transportation Safety Board (NTSB) aviation accident and the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) toxicology and medical certification databases were searched for pilots fatally injured in aviation accidents. During 1990-2012, CAMI received bio-samples of pilots from 7037 aviation accidents. Of these, 2644 cases were positive for drugs. TCAs were present in 31. TCA blood concentrations ranged from therapeutic to toxic levels. The NTSB determined that the use of drugs and ethanol as the probable cause or contributing factor in 35% (11 of 31) of the accidents. None of the 31 pilots reported the use of TCAs during their aviation medical examination. The prevalence of TCAs in aviators was less than 0.5% (31 of 7037 cases). There is a need for aviators to fully disclose the use of medications at the time of their medical examination. © 2016 American Academy of Forensic Sciences.

  14. Lipoxygenase—mediated N—demethylation of imipramine and related tricyclic antidepressants

    Institute of Scientific and Technical Information of China (English)

    HuJA; SajaM

    2002-01-01

    The ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide was examined.Under optimal assay conditions,Vmax values of 14 to 18 mol formaldehyde·min-1·mol-1 enzyme were observed.An inhibition of formaldehyde and desipramine formation by nordihydroguaiaretic acid confirmed the lipoxygenase involvement.The blockade of the reaction by glutathione,dithiothreitol butylated hydroxyanisole (BHA) and butylated hydroxytoluene(BHT) indicated the generation of a free radical intermediate from imipramine.Desipramine,trimipramine,clomipramine,and diltiazem,but not amitriptyline and doxepin,were also oxidized,albeit at a lower rate.Collectively,the evidence gathered in this study suggests,for the first time,that tricyclic antidepressant drugs may undergo lipoxygenase-catalyzed N-demethylation.

  15. The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells.

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    Jeon, Seung-Hyun; Kim, Se Hyun; Kim, Yeni; Kim, Yong Sik; Lim, Yoongho; Lee, Young Han; Shin, Soon Young

    2011-09-23

    In this study, we investigated the antitumor effects of the tricyclic antidepressant 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine (imipramine) on glioma cells. We found that exposure of U-87MG cells to imipramine resulted in the inhibition of PI3K/Akt/mTOR signaling, reduction of clonogenicity, and induction of cell death. Imipramine stimulated the formation of acidic vesicular organelles, the conversion of LC3-I to LC3-II, and the redistribution of LC3 to autophagosomes, suggesting that it stimulates the progression of autophagy. It did not, however, induce apoptosis. We further showed that knockdown of Beclin-1 using siRNA abrogated imipramine-induced cell death. These results suggest that imipramine exerts antitumor effects on PTEN-null U-87MG human glioma cells by inhibiting PI3K/Akt/mTOR signaling and by inducing autophagic cell death.

  16. Use of tricyclic antidepressants and risk of glioma: a nationwide case–control study

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    Pottegård, Anton; García Rodríguez, Luis Alberto; Rasmussen, Lotte; Damkier, Per; Friis, Søren; Gaist, David

    2016-01-01

    Background: A protective effect of tricyclic antidepressants (TCAs) against gliomas has been suggested by a small number of studies. We investigated this putative association in a nationwide setting. Methods: Using a case–control design, we identified all patients with histologically verified glioma (cases) in Denmark between 2000 and 2012 and matched these 1 : 20 to population controls. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) for glioma associated with long-term (⩾3 years) use of TCAs. Similar analyses were performed for selective serotonin reuptake inhibitors (SSRIs). Results: We identified 3767 glioma cases and 75 340 population controls. Long-term use of TCAs was inversely associated with risk of glioma (OR 0.72, 95% CI: 0.41–1.25). Long-term SSRI use was not associated with glioma risk (OR 0.93, 95% CI: 0.75–1.16). Conclusions: Our study indicated that long-term use of TCAs may be associated with a reduced risk of glioma, however, the statistical precision was limited. A similar pattern was not observed for use of SSRIs. PMID:27115466

  17. Chronic Pain Treatment: The Influence of Tricyclic Antidepressants on Serotonin Release and Uptake in Mast Cells

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    Ilonka Ferjan

    2013-01-01

    Full Text Available The involvement of serotonin (5-HT in chronic pain mechanisms is established. 5-HT inhibits central painful stimuli, but recent data suggests that 5-HT could also enhance pain stimulus from the periphery, where mast cells play an important role. We aimed in our study to clarify the influence of selected tricyclic antidepressants (TCAs on mast cell function: secretion, uptake, and reuptake of 5-HT, that could interfere with 5-HT levels and in this way contribute to the generation of pain. As an experimental model, we used isolated rat peritoneal mast cells and incubated them with selected TCAs (clomipramine, amitriptyline, doxepin, and imipramine under different experimental conditions. 5-HT release, uptake, and reuptake were determined spectrofluorometrically. We showed that TCAs were able to inhibit 5-HT secretion from mast cells, as well as uptake of exogenous 5-HT and reuptake of secreted 5-HT back into mast cells. The effects of TCAs were concentration dependent; higher concentrations of TCAs inhibited the secretion of 5-HT induced by compound 48/80, whereas lower concentrations of TCAs inhibited 5-HT uptake. The most effective TCA was halogenated clomipramine. As TCAs are well introduced in chronic pain treatment, the insight into mechanisms of action is important for an understanding of their effect in various pain conditions.

  18. Nonnarcotic analgesics and tricyclic antidepressants for the treatment of chronic nonmalignant pain.

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    Richlin, D M

    1991-05-01

    Chronic nonmalignant pain is often characterized by multiple treatment failures, a pattern of maladaptive behavior, and depression. Often there is a history of inappropriate and excessive use of medications for pain. Prior and ongoing use of narcotics and sedatives acts to compound and aggravate the chronic pain syndrome. A first step in treatment is controlled withdrawal of these agents. Nonnarcotic analgesics, NSAIDs, and tricyclic antidepressants are commonly employed in patients with chronic pain. Effective use of these agents requires understanding of their pharmacokinetic and pharmacodynamic properties. Use of a fixed-time schedule is necessary to achieve an effective, sustained therapeutic response. Careful patient education and monitoring for side effects and toxicity are necessary, particularly in the elderly and patients with coexisting medical disorders. Incidence of side effects and toxicity may be reduced by choice of drug and modification of dosing regimen. Nonnarcotic analgesics, TCAs, and NSAIDs are seldom effective by themselves in resolving the pain and distress of patients with chronic nonmalignant pain. This is particularly true when maladaptive behavior coexists. A comprehensive multimodal pain management program encompassing additional pain-relieving strategies and behavior-modifying techniques should be considered and utilized in conjunction with medication.

  19. Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.

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    Molana, Aliasghar; Mehrpour, Masoud; Vousooghi, Nasim; Hajighasem, Mahmoud Reza; Joghataei, Mohammad Taghi

    2014-07-04

    Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO) may act as genetic factors for migraine. NO synthase 3 (NOS3) by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs). The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks. A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st) month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd) month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO. The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05). Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable factor for better response to TCAs in reducing migraine attacks in comparison to GT and GG genotypes.

  20. Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.

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    Aliasghar Molana

    2014-09-01

    Full Text Available Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO may act as genetic factors for migraine. NO synthase 3 (NOS3 by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs. The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks.A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO.The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P < 0.05. Mean intensity of headaches in patients with TT genotype was lower in comparison to GT and GG genotypes before and after use of TCAs (based on verbal numerical rating scale. Mean frequency of migraine attacks after use of TCAs was significantly decreased in all genotypes of NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05.Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable

  1. Quantification of Tricyclic Antidepressants in Serum Using Liquid Chromatography Electrospray Tandem Mass Spectrometry (HPLC-ESI-MS/MS).

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    Crutchfield, Christopher A; Breaud, Autumn R; Clarke, William A

    2016-01-01

    Tricyclic antidepressants (TCA) are used to treat major depressive disorder and other psychological conditions. The efficacy of these drugs is tied to a narrow therapeutic window. Inappropriately high drug concentrations can result in serious side effects such as hypotension, tachycardia, or coma. As a result, concentrations of tricyclic antidepressants are routinely monitored to ensure compliance and to prevent adverse side effects by dose adjustments. We describe a method for the determination of concentrations of amitriptyline, desipramine, imipramine, and nortriptyline in human serum using high-performance liquid chromatography coupled to a tandem mass spectrometer with electrospray ionization (HPLC-ESI-MS/MS). The method is rapid, requiring only 3.5 min per analysis. The method requires 100 μL of serum. Concentrations of each TCA were quantified by a calibration curve relating the peak area ratio of each TCA analyte to a deuterated internal standard (amitriptyline-D3, desipramine-D3, imipramine-D3, and nortriptyline-D3). The method was linear from ~70 ng/mL to ~1000 ng/mL for all TCAs, with imprecision ≤ 12%.

  2. Inhibition of /sup 22/Na influx by tricyclic and tetracyclic antidepressants and binding of (/sup 3/H)imipramine in bovine adrenal medullary cells

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    Arita, M.; Wada, A.; Takara, H.; Izumi, F.

    1987-10-01

    In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. (/sup 3/H)Imipramine bound specifically to adrenal medullary cells. Binding was saturable, reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of (/sup 3/H)imipramine at the same concentrations as they inhibited /sup 22/Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of (/sup 3/H)imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.

  3. Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors: an involvement of astrocytes.

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    Shuken Boku

    Full Text Available Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG, which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP, we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI, a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA. These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.

  4. Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder.

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    Meltzer, H; Bastani, B; Jayathilake, K; Maes, M

    1997-07-01

    It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity. The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol and prolactin (PRL) concentrations were studied in patients with major depression or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD. The L-5-HTP-induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different. The results suggest that fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated stimulation of cortisol and PRL secretion in humans, consistent with available evidence that fluoxetine treatment, but not tricyclic antidepressants, increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism.

  5. Evaluation of thermodynamic parameters of amphiphilic tricyclic antidepressant drug imipramine hydrochloride-additive systems at the cloud point.

    Science.gov (United States)

    Alam, Md Sayem; Kabir-ud-Din; Mandal, Asit Baran

    2010-04-01

    Cloud point (CP) of an amphiphile can be considered as the limit of its solubility as it phase separates at temperatures above the CP. The clouding components release their solvated water and separate out from the solution. In the present paper, we report the thermodynamics of clouding in amphiphilic drug, imipramine hydrochloride (IMP-a tricyclic antidepressant drug), in the presence of additives (viz., alcohols and surfactants). Surfactants are extensively used in drug delivery as drug carriers. For all cases the standard Gibbs energy change of solubilization (DeltaGs0) is evaluated and, found to be positive. However, the standard enthalpy change (DeltaHs0), and the product of standard entropy change and temperature (TDeltaSs0) values are found negative as well as positive. These values are depending upon the type and nature of the additive, and the results are discussed on the basis of these factors. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  6. Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies.

    Science.gov (United States)

    Wu, Qing; Qu, Wenchun; Crowell, Michael D; Hentz, Joseph G; Frey, Keith A

    2013-04-01

    Because studies of the association between tricyclic antidepressant (TCA) treatment and risk of fracture have shown inconsistent findings, we sought to assess whether people who take TCAs are at increased risk of fracture. Relevant studies published by June 2012 were identified through database searches of Scopus, MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and WorldCat Dissertations and Theses from their inception, and manual searching of reference lists. Only original studies that examined the association between TCA treatment and risk of fracture were included. Two investigators independently conducted literature searches, study selection, study appraisal, and data abstraction using a standardized protocol. Disagreements were resolved by consensus. Twelve studies met inclusion criteria. Because of the heterogeneity of these studies, random-effects models were used to pool estimates of effect. Overall, TCA use was associated with significantly increased fracture risk (relative risk [RR], 1.45; 95% confidence interval [CI], 1.31-1.60; p < 0.001). Increased fracture risk associated with TCA use was also observed in studies that adjusted for bone mineral density (RR, 1.54; 95% CI, 1.24-1.90; p < 0.001) or depression (RR, 1.49; 95% CI, 1.28-1.67; p < 0.001). Strength of association with TCA exposure duration ≥6 weeks (RR, 1.13; 95% CI, 1.00-1.28) was substantially weaker than association with TCA exposure duration <6 weeks (RR, 2.40; 95% CI, 1.41-4.08). Prior TCA exposure had no significant effect on fracture risk (RR, 1.04; 95% CI, 0.86-1.26; p = 0.70). After accounting for publication bias, we found the overall association between TCA use and fracture risk to be slightly weaker (RR, 1.36; 95% CI, 1.24-1.50) but still significant (p < 0.001). Findings of this meta-analysis indicate that treatment with TCAs may convey an increased risk of fracture, independent of depression and bone mineral density.

  7. 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

  8. Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants.

    Science.gov (United States)

    Bagheri, H; Schmitt, L; Berlan, M; Montastruc, J L

    1992-01-01

    The effect of yohimbine treatment (4 mg three times daily) for 3 weeks on salivary secretion was investigated. In healthy volunteers, acute administration of yohimbine increased salivary volume within 1 h to a similar extent before and at the end of the treatment period. In depressed patients treated with tricyclic antidepressants (and exhibiting a reduced salivary flow), yohimbine also acutely increased salivary volume. In contrast, the alpha 2-adrenoceptor antagonist failed to modify resting values measured in the morning (i.e. 10 and 14 h after the last administration in healthy volunteers and depressed patients respectively). This result indicates that alpha 2-adrenoceptor antagonists may have a potential therapeutic use in the treatment of dry mouth caused by tricyclic antidepressant drugs. PMID:1362888

  9. Arterial Blood Gas Analysis and the Outcome of Treatment in Tricyclic Antidepressants Poisoned Patients with Benzodiazepine Coingestion

    Directory of Open Access Journals (Sweden)

    Ahmad Yaraghi

    2015-01-01

    Full Text Available Background. Poisoning with tricyclic antidepressants (TCAs is still a major concern for emergency physicians and intensivists. Concomitant ingestion of other psychoactive drugs especially benzodiazepines with TCAs may make this clinical situation more complex. This study aimed to compare the arterial blood gas (ABG values and the outcome of treatment in patients with coingestion of TCA and benzodiazepine (TCA + BZD poisoning and TCA poisoning alone. Methods. In this cross-sectional study which was carried out in a tertiary care university hospital in Iran, clinical and paraclinical characteristics of one hundred forty TCA only or TCA + BZD poisoned patients (aged 18–40 years were evaluated. ABG analysis was done on admission in both groups. Outcomes were considered as survival with or without complication (e.g., intubation and the frequency of TCA poisoning complications. Results. Arterial pH was significantly lower in TCA + BZD poisoning group compared with TCA only poisoning group (7.34 ± 0.08 and 7.38 ± 0.08, resp.; P=0.02. However, other complications such as seizure, and the need for the endotracheal intubation were not significantly different. All patients in both groups survived. Conclusions. Concomitant TCA plus BZD poisoning may make the poisoned patients prone to a lower arterial pH level on hospital admission which may potentially increases the risk of cardiovascular complications in TCA poisoning.

  10. Effect of tricyclic antidepressants on transmitter-stimulated inositol phosphate production in rat brain cortex in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, S.; Enna, S.J.

    1986-03-01

    Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar in the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.

  11. Oxidation of tricyclic antidepressant drugs with chloramine-T in acidic solutions: kinetic, mechanistic and thermodynamic studies.

    Science.gov (United States)

    Sukhdev, Anu; Puttaswamy, Puttaswamy

    2013-12-01

    The kinetics of the oxidation of two tricyclic antidepressants (TCA) namely, imipramine (IMP) and clomipramine (CLM) with sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in HClO4 medium was studied at 300 K. The two reactions followed identical kinetics with a first-order dependence of rate on [CAT]o and fractional order dependence on [TCA]o. The reaction is catalyzed by H(+) ions with a fractional order dependence. The reaction was studied at different temperatures and activation parameters were evaluated. The reaction constants involved in the mechanism were computed. The solvent isotope effect was studied using D2O. Addition of p-toluenesulfonamide retards the reaction rate. The rate increased with decreasing dielectric constant of the medium. Variation of ionic strength of the medium and addition of halide ions (Cl(-) or Br(-)) showed no effect on the rate. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as imipramine-5-N-oxide and clomipramine-5-N-oxide. The rate of oxidation of IMP is faster than CLM. The observed results have been explained in terms of a mechanism and a relevant rate law has been deduced.

  12. Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ehrnrooth, E.; Grau, C.; Zachariae, R.; Andersen, Joern [Aarhus Univ. Hospital (Denmark). Dept. of Oncology

    2001-11-01

    Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation-induced mucositis pain. Forty-three patients receiving 66-68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p=0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment.

  13. The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors.

    Science.gov (United States)

    Nojimoto, F D; Mueller, A; Hebeler-Barbosa, F; Akinaga, J; Lima, V; Kiguti, L R de A; Pupo, A S

    2010-01-01

    Although it is long known that the tricyclic antidepressants amitriptyline, nortriptyline and imipramine inhibit the noradrenaline transporter and alpha(1)-adrenoceptors with similar affinities, which may lead to self-cancelling actions, the selectivity of these drugs for alpha(1)-adrenoceptor subtypes is unknown. The present study investigates the selectivity of amitriptyline, nortriptyline and imipramine for human recombinant and rat native alpha(1)-adrenoceptor subtypes. The selectivity of amitriptyline, nortriptyline and imipramine was investigated in HEK-293 cells expressing each of the human alpha(1)-subtypes and in rat native receptors from the vas deferens (alpha(1A)), spleen (alpha(1B)) and aorta (alpha(1D)) through [(3)H]prazosin binding, and noradrenaline-induced intracellular Ca(2+) increases and contraction assays. Amitriptyline, nortriptyline and imipramine showed considerably higher affinities for alpha(1A)- (approximately 25- to 80-fold) and alpha(1D)-adrenoceptors (approximately 10- to 25-fold) than for alpha(1B)-adrenoceptors in both contraction and [(3)H]prazosin binding assays with rat native and human receptors, respectively. In addition, amitriptyline, nortriptyline and imipramine were substantially more potent in the inhibition of noradrenaline-induced intracellular Ca(2+) increases in HEK-293 cells expressing alpha(1A)- or a truncated version of alpha(1D)-adrenoceptors which traffics more efficiently towards the cell membrane than in cells expressing alpha(1B)-adrenoceptors. Amitriptyline, nortriptyline and imipramine are much weaker antagonists of rat and human alpha(1B)-adrenoceptors than of alpha(1A)- and alpha(1D)-adrenoceptors. The differential affinities for these receptors indicate that the alpha(1)-adrenoceptor subtype which activation is most increased by the augmented noradrenaline availability resultant from the blockade of neuronal reuptake is the alpha(1B)-adrenoceptor. This may be important for the behavioural effects of these

  14. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants.

    Science.gov (United States)

    Boehnert, M T; Lovejoy, F H

    1985-08-22

    There is a need for a rapid predictor of potential clinical severity to guide therapy in patients with an acute overdose of tricyclic antidepressant drugs. We performed a prospective study of 49 such patients to observe the associations among serum drug levels, maximal limb-lead QRS duration, and the incidence of seizures and ventricular arrhythmias. Patients were divided into two groups on the basis of maximal limb-lead QRS duration. Group A (13 patients) had a duration of less than 0.10 second, and Group B (36 patients) had a QRS duration of 0.10 second or longer. No seizures or ventricular arrhythmias occurred in Group A. In Group B there was a 34 per cent incidence of seizures and a 14 per cent incidence of ventricular arrhythmias. All patients survived. Serum drug levels failed to predict the risk of seizures or ventricular arrhythmias accurately. Seizures occurred at any QRS duration of 0.10 second or longer (P less than 0.05), but ventricular arrhythmias were seen only with a QRS duration of 0.16 second or longer (P less than 0.0005). We conclude that determination of the maximal limb-lead QRS duration predicts the risk of seizures and ventricular arrhythmias in acute overdose with tricyclic antidepressants. Serum drug levels are not of predictive value.

  15. 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

    -function relationships. However, the precise structural mechanism by which antidepressants inhibit hSERT and the location of their binding pockets are still elusive. We have identified a residue (Ser-438) located within the 5HT-binding pocket in hSERT to be a critical determinant for the potency of several...

  16. A simple dried blood spot method for therapeutic drug monitoring of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their active metabolites using LC-MS/MS.

    Science.gov (United States)

    Berm, E J J; Paardekooper, J; Brummel-Mulder, E; Hak, E; Wilffert, B; Maring, J G

    2015-03-01

    Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCAs) is considered useful in patients with major depressive disorder, since these drugs display large individual differences in clearance, and the therapeutic windows of these drugs are relatively small. We developed an assay for determination of amitriptyline (ATP), nortriptyline (NTP), imipramine (IMP), desipramine (DSP) clomipramine (CMP) and desmethyl-clomipramine (DCMP) in dried blood spots (DBS). A fast and robust LC-MS/MS method was developed and analytically validated for simultaneous determination of ATP, NTP, IMP, DSP, CMP, and DCMP in DBS. Six mm circles were punched out from DBS collected on Whatman DMPK-C paper and mixed with acetonitrile: methanol 1:3 containing the internal standard. The extract was analyzed by LC-MS/MS. Total LC-MS/MS runtime was 4.8 min. The assay was linear in the range 20-500 µg/L for all compounds. Overall-assay accuracy and precision were15% negative bias for all compounds. Punching at the perimeter of the blood spot instead of the center was associated with a positive bias. A good correlation was found between patients plasma and DBS samples of ATP, NTP and DMCP, but not for CMP. In addition, proportional differences were found. This LC-MS/MS method was analytically validated for determination of TCAs in DBS. Future validation will focus on the clinical application of the method.

  17. Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2 : Testing the hypotheses

    NARCIS (Netherlands)

    Nijenhuis, Cynthia M.; ter Horst, Peter G. J.; van Rein, Nienke; Wilffert, Bob; de Jong-van den Berg, Lolkje T. W.

    2012-01-01

    AIMS Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication

  18. Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism.

    Science.gov (United States)

    Andrés, J Ignacio; Alcázar, Jesús; Alonso, José M; Alvarez, Rosa M; Bakker, Margot H; Biesmans, Ilse; Cid, José M; De Lucas, Ana I; Drinkenburg, Wilhelmus; Fernández, Javier; Font, Luis M; Iturrino, Laura; Langlois, Xavier; Lenaerts, Ilse; Martínez, Sonia; Megens, Anton A; Pastor, Joaquín; Pullan, Shirley; Steckler, Thomas

    2007-06-01

    In previous articles we have described the discovery of a new series of tricyclic isoxazolines combining central serotonin (5-HT) reuptake inhibition with alpha(2)-adrenoceptor antagonistic activity. We report now on the synthesis, the in vitro binding potency and the primary in vivo activity of six enantiomers within this series, one of which was selected for further pharmacological evaluation and assigned as R226161. Some additional in vivo studies in rats are described with this compound, which proved to be centrally and orally active as a combined 5-HT reuptake inhibitor and alpha(2)-adrenoceptor antagonist.

  19. Steric hindrance mutagenesis in the conserved extracellular vestibule impedes allosteric binding of antidepressants to the serotonin transporter

    DEFF Research Database (Denmark)

    Plenge, Per; Shi, Lei; Beuming, Thijs;

    2012-01-01

    The serotonin transporter (SERT) controls synaptic serotonin levels and is the primary target for antidepressants, including selective serotonin reuptake inhibitors (e.g. (S)-citalopram) and tricyclic antidepressants (e.g. clomipramine). In addition to a high affinity binding site, SERT possesses...

  20. Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells.

    Science.gov (United States)

    Hisaoka-Nakashima, Kazue; Miyano, Kanako; Matsumoto, Chie; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yokoyama, Akinobu; Uezono, Yasuhito; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2015-05-29

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gα(i/o) inhibitor, but not by NF449, a Gα(s) inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gα(ο1) and Gα(i3) by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKey(TM) assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gα(i/o) activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gα(i/o) upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants.

  1. 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

  2. What is an antidepressant binding site doing in a bacterial transporter?

    Science.gov (United States)

    Rudnick, Gary

    2007-09-21

    LeuT is a bacterial amino acid transporter belonging to a large family of membrane proteins, including the neurotransmitter transporters that are targets for antidepressant drugs. The high-resolution structure of LeuT has provided an important model for understanding structure and function in this family. Two recent papers found that LeuT can bind tricyclic antidepressants, raising the possibility that it may also serve as a model for the pharmacological properties of neurotransmitter transporters.

  3. Tratamento de idosos com depressão utilizando tricíclicos, IMAO, ISRS e outros antidepressivos Depression treatment of elderly patients using tricyclics, MAOI, SSRI, and other antidepressants

    Directory of Open Access Journals (Sweden)

    Mônica Z Scalco

    2002-04-01

    Full Text Available Antidepressivos são eficazes no tratamento da depressão em idosos. O sucesso do tratamento depende do tipo e da gravidade da depressão; das comorbidades com outras doenças psiquiátricas ou clínicas; da escolha adequada de antidepressivos, de sua eficácia e perfil de efeitos adversos; da orientação do paciente e de sua aderência ao tratamento. O manejo dos efeitos adversos em pacientes idosos, que usam muito mais medicações e apresentam mais doenças, é o ponto forte na escolha de antidepressivos. Em geral, os inibidores seletivos da recaptação de serotonina têm sido preferidos por apresentar menos riscos de complicações por efeitos adversos. Porém, diferentes antidepressivos podem ser preferíveis para diferentes pacientes. É indispensável que o médico conheça o paciente que irá tratar e o perfil de efeitos adversos e de possíveis interações medicamentosas dos antidepressivos para poder escolher o mais adequado para cada paciente. Neste artigo, são abordados os diferentes grupos de antidepressivos no tratamento agudo da depressão em idosos e o tratamento em populações especiais de idosos (idosos debilitados e idosos com demência.Antidepressants are effective in treating depression in the elderly. Treatment response depends on the type and severity of depression, comorbidities, efficacy and tolerability of antidepressants, patient education and treatment compliance. The aging process leads to physiological changes that, in association with concomitant diseases and use of several medications, render the elderly person more vulnerable to the adverse effects of antidepressants and an increased risk of drug interactions. It is very important that psychiatrists treating elderly patients be aware of possible adverse effects and drug interactions of different antidepressants. This paper reviews data on the efficacy and safety of antidepressant agents currently available for the treatment of the elderly, and includes

  4. Memory Impairment following Acute Tricyclic Antidepressants Overdose

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    Nastaran Eizadi-Mood

    2015-01-01

    Full Text Available Background. Psychiatric consultation is necessary for all patients with intentional poisoning and its reliability depends on the proper function of patients’ memory performance. This study aimed to determine the possible memory impairment following acute TCAs’ poisoning. Materials and Methods. In this cross-sectional study, patients with acute TCAs poisoning were allocated to two groups of severe poisoning (with coma, seizures, cardiac arrhythmias, hypotension, and a wide QRS complex and mild-to-moderate poisoning according to their clinical presentation at the time of hospital admission. All patients underwent memory performance test both immediately and 24 hours after their initial consciousness after admission, using Wechsler Memory Scale (WMS-IV. Results. During the study period, 67 TCA-poisoned patients (aged, 20–64 years were evaluated, of which 67.2% were female. The mean memory scores of patients immediately and 24 hours after the initial consciousness were 31.43±9.02 and 50.62±9.12, respectively (P<0.001. Twenty-four hours after the initial consciousness, memory score was statistically correlated with the amount of ingested drug and the intoxication severity. Conclusion. Following the recovery from somatic symptoms of acute TCA poisoning, patients may still suffer from memory impairment and it seems that this time is not suitable for performing a reliable psychiatric consultation.

  5. Mechanisms of antidepressant resistance

    Directory of Open Access Journals (Sweden)

    Wissam eEl Hage

    2013-11-01

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

  6. Antidepressants for patients with tinnitus.

    Science.gov (United States)

    Baldo, Paolo; Doree, Carolyn; Molin, Paola; McFerran, Don; Cecco, Sara

    2012-09-12

    This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms. To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit is due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; PsycINFO; CINAHL; Web of Science; BIOSIS; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 5 January 2012. Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus. Two authors critically appraised the retrieved studies and extracted data independently. Where necessary we contacted study authors for further information. Six trials involving 610 patients were included. Trial quality was generally low. Four of the trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. One study investigated trazodone, an atypical antidepressant, versus placebo. Only the trial using the SSRI drug reached the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop-out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the

  7. [The research of new antidepressants: present orientations (author's transl)].

    Science.gov (United States)

    Fieve, R R

    1979-01-01

    A number of promising antidepressant compounds are presently either being developed in the laboratory or are being tested clinically by pharmaceutical firms and universities around the world. New compounds are sought which will provide: 1. fewer side effects, particularly anticholinergic and cardiovascular effects; 2. more rapid onset of action than 7-10 days required of most antidepressants now used; 3. efficacy in a higher percentage of patients than the 65-70 per cent estimated to respond to currently available antidepressant therapies. Compounds now being investigated include: new tricyclics which are unlike those commonly in use; the tetracyclics; the salts of naturally occurring cations such as lithium and rubidium; and various chemically unrelated new compounds. In addition, several drugs currently being tested as anorectics seem promising for future antidepressant drugs research.

  8. 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

  9. The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine.

    Science.gov (United States)

    Cussotto, Sofia; Cryan, John F; O'Leary, Olivia F

    2017-03-27

    Approximately 50% of depressed individuals fail to achieve remission with first-line antidepressant drugs and a third remain treatment-resistant. When first-line antidepressant treatment is unsuccessful, second-line strategies include dose optimisation, switching to another antidepressant, combination with another antidepressant, or augmentation with a non-antidepressant medication. Much of the evidence for the efficacy of augmentation strategies comes from studies using lithium to augment the effects of tricyclic antidepressants. The neural circuitry underlying the therapeutic effects of lithium augmentation is not yet fully understood. Recently, we reported that chronic treatment with a combination of lithium and the antidepressant desipramine, exerted antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that did not exhibit an antidepressant-like behavioural response to either drug alone. In the present study, we used this model in combination with ΔFosB/FosB immunohistochemistry to identify brain regions chronically affected by lithium augmentation of desipramine when compared to either treatment alone. The data suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal hippocampus are key nodes in the neural circuitry underlying antidepressant action of lithium augmentation of desipramine. These data give new insight into the neurobiology underlying the mechanism of lithium augmentation in the context of treatment-resistant depression.

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

    OpenAIRE

    Bosch, O G; Quednow, B. B.; Seifritz, E.; Wetter, T C

    2012-01-01

    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) syste...

  11. The Association between Antidepressant Medications and Coronary Heart Disease in Brazil: A Cross-sectional Analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil

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    Andrew eKemp

    2015-01-01

    Full Text Available Background: Recent studies have highlighted associations between use of antidepressant medications and coronary heart disease (CHD. Tricyclic antidepressants are not recommended in patients with CHD as they may increase morbidity and mortality. However, this class of antidepressants are freely prescribed in public health pharmacies, while access to other classes of antidepressants is restricted in Brazil. Here we examine the associations between antidepressant use and prevalent CHD in a large cohort from Brazil. Methods: Participants included 14,994 civil servants aged 35 to 74 from the baseline assessment of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil. CHD (n=710 included stable angina, myocardial infarction and coronary revascularization. Univariate (unadjusted and multivariate (adjusted logistic regression analyses were conducted to estimate odds ratios and confidence intervals. Results: After full adjustment for covariates, tricyclic antidepressants (TCA use (n=156 was associated with a 2-fold increase in prevalent CHD, relative to non-use (n=14,076. Additional sensitivity analysis revealed a three-fold association for myocardial infarction (OR: 2.962, 95% CI: 1.413-6.210 and coronary revascularization (OR: 2.915, 95% CI: 1.275-6.662. There were no significant associations between antidepressant use and stable angina pectoris. Conclusions: Findings highlight a strong association between TCA use and prevalent CHD. While the cross-sectional design is an important limitation of the present study, findings have important implications for the treatment of cardiac patients in Brazil.

  12. Cardiovascular Effects of Antidepressants and Mood Stabilizers

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    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.

  13. Mechanisms of antidepressant resistance

    Science.gov (United States)

    El-Hage, Wissam; Leman, Samuel; Camus, Vincent; Belzung, Catherine

    2013-01-01

    Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant (AD) properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder (MDD). However, there is a wide range of variability in response to ADs that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to AD therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier (BBB) function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes. PMID:24319431

  14. [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.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Citalopram versus other anti-depressive agents for depression

    Science.gov (United States)

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

    2014-01-01

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

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

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    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

  18. Invited review: the evolution of antidepressant mechanisms.

    Science.gov (United States)

    Slattery, D A; Hudson, A L; Nutt, D J

    2004-02-01

    Present antidepressants are all descendents of the serendipitous findings in the 1950s that the monoamine oxidase inhibitor iproniazid and the tricyclic antidepressant imipramine were effective antidepressants. The identification of their mechanism of action, and those of reserpine and amphetamine, in the 1960s, led to the monoamine theories of depression being postulated; first, with noradrenaline then 5-hydroxytryptamine being considered the more important amine. These monoamine theories of depression predominated both industrial and academic research for four decades. Recently, in attempts to design new drugs with faster onsets of action and more universal therapeutic action, downstream alterations common to current antidepressants are being examined as potential antidepressants. Additionally, the use of animal models has identified a number of novel targets some of which have been subjected to clinical trials in humans. However, monoamine antidepressants remain the best current medications and it may be some time before they are dislodged as the market leaders.

  19. Compliance and persistence of antidepressants versus anticonvulsants in patients with neuropathic pain during the first year of therapy.

    Science.gov (United States)

    Gharibian, Derenik; Polzin, Jennifer K; Rho, Jay P

    2013-05-01

    Neuropathic pain (NP) is a chronic condition that has human, social, and economic consequences. A variety of agents can be used for treatment; however, antidepressants and anticonvulsants are the 2 classes most widely studied and represent first-line agents in the management of NP. Little information is known about the adherence patterns of these medications during the first year of therapy in patients with NP. To examine the compliance and persistence of antidepressants versus anticonvulsants in patients with NP during the first year of therapy. Using electronic medical and pharmacy data for the Kaiser Permanente Southern California region, the adherence patterns for patients with a NP diagnosis prescribed an antidepressant or an anticonvulsant were studied. Compliance and persistence were measured using the medication possession ratio and the Refill-Sequence model, respectively. The study included 1817 patients with NP diagnosis taking either an antidepressant or an anticonvulsant. Within the antidepressant group, 42.9% were considered compliant, compared with 43.7% in the anticonvulsant group. Subanalysis of the 2 cohorts revealed that patients on venlafaxine were the most compliant (69.4%) compared with patients taking gabapentin (44.4%) and tricyclic antidepressants (41.8%) (Panticonvulsant group were considered persistent with their medication refills. Compliance and persistence rates were similar for patients with NP diagnosis taking antidepressants and anticonvulsants. Higher compliance was observed among patients taking venlafaxine; however, this population did have a small sample size.

  20. Heart Rate Variability in Children with Tricyclic Antidepressant Intoxication

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    Ener Cagri Dinleyici

    2013-01-01

    Full Text Available The aim of this study was to evaluate HRV in children requiring intensive care unit stays due to TCA poisoning between March 2009 and July 2010. In the time-domain nonspectral evaluation, the SDNN (P<0.001, SDNNi (P<0.05, RMSDD (P<0.01, and pNN50 (P<0.01 were found to be significantly lower in the TCA intoxication group. The spectral analysis of the data recorded during the first 5 minutes after intensive care unit admission showed that the values of the nLF (P<0.05 and the LF/HF ratio (P=0.001 were significantly higher in the TCA intoxication group, while the nHF (P=0.001 values were significantly lower. The frequency-domain spectral analysis of the data recorded during the last 5 minutes showed a lower nHF (P=0.001 in the TCA intoxication group than in the controls, and the LF/HF ratio was significantly higher (P<0.05 in the intoxication group. The LF/HF ratio was higher in the seven children with seizures (P<0.001. These findings provided us with a starting point for the value of HRV analysis in determining the risk of arrhythmia and convulsion in TCA poisoning patients. HRV can be used as a noninvasive testing method in determining the treatment and prognosis of TCA poisoning patients.

  1. Prescription of antidepressants to patients on opioid maintenance therapy – a pharmacoepidemiological study

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    Ingeborg Hartz

    2011-12-01

    Full Text Available Background and aims: Depression and anxiety are commonly reported among patients in opioid maintenance treatment (OMT. The aim of the present study was to describe aspects of prescription of antidepresant drug therapy among patients on OMT. Our research questions were: 1 What is the prevalence of antidepressant use according to age and gender? 2 Which antidepressants are used? 3 How are antidepressants used in terms of reimbursement codes, dispensed dose and duration of therapy?Methods: Pharmacoepidemiological data were retrieved from the complete national Norwegian Prescription Database which contains information on all prescription drugs (such as Anatomical Theraputical Chemical (ATC-code, Defined Daily Dose (DDDs, dispensed at pharmacies to individual patients. Norwegian OMT-patients (N=4374, 3035 men and 1339 women who received methadone mixture, buprenorphine capsules or combined buprenorphine-naloxone capsules for at least 6 months in 2009 were included. Prevalence of antidepressant use in the studied patients was measured in terms of retrieval of prescriptions.Results: During 2009 21.7% of the studied patients filled at least one prescription for an antidepressant drugs (men: 21.2%; women: 22.9%. The subgroup of antidepressants most frequently dispensed was selective serotonin reuptake inhibitors (SSRIs (33%, followed by the sedative antidepressants mianserin and mirtazapin (22% and tricyclic antidepressants (TCAs (20%. Except for TCAs, prescriptions of all antidepressant subgroups were reimbursed for either anxiety or depression in 90% of the cases. Overall, 46.9% of the antidepressant users were prescribed antidepressants in the category < 1 DDD per day and/or treatment < 3 months, with no gender difference.Conclusions: About one out of five OMT-patients filled a prescription for an antidepressant drug in 2009. Above 90% had their prescriptions reimbursed for either depression or anxiety. Use at low doses and/or sporadic use among half

  2. Unravelling the efficacy of antidepressants as analgesics.

    Science.gov (United States)

    Janakiraman, Raguraman; Hamilton, Laura; Wan, Aston

    2016-03-01

    Chronic pain is a large and growing public health concern in Australia. Chronic pain is generally associated with physical, psychological, social and cultural risk factors. Several antidepressants have been efficacious in the management of chronic pain. This article illustrates the use of antidepressants in major chronic neuropathic pain conditions. Knowledge of psychopharmacology is important in the management of chronic pain. The majority of patients with chronic pain have comorbid psychiatric conditions ranging from mild anxiety, depression and adjustment problems, to severe delusional and psychotic disorders. Depression and anxiety are known to enhance the perception of pain. Not all antidepressants have independent analgesic properties. There is now a convincing body of controlled data, as well as extensive longstanding clinical experience, supporting tricyclic antidepressants (TCAs) as analgesics independently of their antidepressant actions.

  3. 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

  4. 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.

  5. Antidepressant Withdrawal

    Science.gov (United States)

    Diseases and Conditions Depression (major depressive disorder) If you stop taking antidepressants, could you experience antidepressant withdrawal? Do withdrawal symptoms mean you were addicted to the drug? Answers from Daniel K. Hall-Flavin, M.D. Antidepressant withdrawal is possible if you ...

  6. Musical Hallucinations And Antidepressants: Case Report Involving Serotoninergic Ways

    OpenAIRE

    1998-01-01

    A case of musical hallucination (MII) triggered by different antidepressive drugs is described. This is an uncommon side effect, probably more related to individual factors than to high doses. Musical hallucinations seems to be a releasing phenomenon, associated to sensorial deficit and neuronal compensatory activation. The present case report suggests that not only classical tricyclic antidepressives (AD) can cause MH, but also more selective drugs such as the SSRIs and venlafaxine. Aminedip...

  7. 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

  8. Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights.

    Science.gov (United States)

    Kremer, Mélanie; Salvat, Eric; Muller, André; Yalcin, Ipek; Barrot, Michel

    2016-12-03

    Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory system. It is generally chronic and challenging to treat. The recommended pharmacotherapy for neuropathic pain includes the use of some antidepressants, such as tricyclic antidepressants (TCAs) (amitriptyline…) or serotonin and noradrenaline re-uptake inhibitors (duloxetine…), and/or anticonvulsants such as the gabapentinoids gabapentin or pregabalin. Antidepressant drugs are not acute analgesics but require a chronic treatment to relieve neuropathic pain, which suggests the recruitment of secondary downstream mechanisms as well as long-term molecular and neuronal plasticity. Noradrenaline is a major actor for the action of antidepressant drugs in a neuropathic pain context. Mechanistic hypotheses have implied the recruitment of noradrenergic descending pathways as well as the peripheral recruitment of noradrenaline from sympathetic fibers sprouting into dorsal root ganglia; and importance of both α2 and β2 adrenoceptors have been reported. These monoamine re-uptake inhibitors may also indirectly act as anti-proinflammatory cytokine drugs; and their therapeutic action requires the opioid system, particularly the mu (MOP) and/or delta (DOP) opioid receptors. Gabapentinoids, which target the voltage-dependent calcium channels α2δ-1 subunit, inhibit calcium currents, thus decreasing the excitatory transmitter release and spinal sensitization. Gabapentinoids also activate the descending noradrenergic pain inhibitory system coupled to spinal α2 adrenoceptors. Gabapentinoid treatment may also indirectly impact on neuroimmune actors, like proinflammatory cytokines. These drugs are effective against neuropathic pain both with acute administration at high dose and with repeated administration. This review focuses on mechanistic knowledge concerning chronic antidepressant treatment and gabapentinoid treatment in a neuropathic pain context. Copyright © 2016 IBRO. Published by

  9. /sup 13/C NMR studies of the molecular flexibility of antidepressants

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-02-01

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

  10. Clonidine as a sensitizing agent in the forced swimming test for revealing antidepressant activity.

    OpenAIRE

    1991-01-01

    The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs having beta adrenoreceptor agonist activity and for serotonin uptake inhibitors. We investigated the potential for clonidine to render the FST sensitive to antidepressants by using a behaviorally inactive dose of this agent (0.1 mg/kg). All antidepressants studied (tricyclics, 5-HT uptake inhibitors, iprindole, mianserin, viloxazine, trazodone) showed either activity at lower doses or activity at pr...

  11. Oxidative rearrangements of tricyclic vinylcyclobutane derivatives

    OpenAIRE

    Grota, Juliane; Mattay, Jochen; Piech, Krzysztof; Bally, Thomas

    2006-01-01

    Three tricyclic vinylcyclobutanes (3-methylenetricyclo[5.3.0.02,6]decanes 1-3) have been subjected to ionization by photoinduced electron transfer in solution and by X-irradiation in Ar matrices. All three compounds undergo oxidative cycloreversion; the cleavage of the four-membered ring, however, occurs in a different direction depending on the presence of a methyl group in position 6 of the tricyclic framework. In those derivatives, cycloreversion is found to lead to 1-methyl-8-methylene-1,...

  12. Effects of antidepressants, but not psychopathology, on cardiac sympathetic control: a longitudinal study.

    Science.gov (United States)

    Licht, Carmilla M M; Penninx, Brenda W J H; de Geus, Eco J C

    2012-10-01

    Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of antidepressant medication. The aim of this study was to test longitudinally whether cardiac sympathetic control, measured by pre-ejection period (PEP), was increased by depression/anxiety status and by antidepressant use. Cross-sectional and longitudinal data were from a depression and anxiety cohort: the Netherlands Study of Depression and Anxiety (NESDA). Baseline data of 2838 NESDA subjects (mean age 41.7 years, 66.7% female) and 2-year follow-up data of 2226 subjects were available for analyses. Included were subjects with and without depressive/anxiety disorders, using or not using different antidepressants at baseline or follow-up. The PEP was measured non-invasively by 1.5 h of ambulatory impedance cardiography. Cross-sectional analyses compared PEP across psychopathology and antidepressant groups. Longitudinal analyses compared 2-year changes in PEP in relation to changes in psychopathology and antidepressant use. Cross-sectional analyses showed that antidepressant-naïve depressive/anxious subjects had comparable PEP as controls, whereas subjects using tricyclic (TCA) or combined serotonergic/noradrenergic antidepressants (SNRI) had significantly shorter PEP compared with controls. In contrast, subjects using selective serotonin re-uptake inhibitors (SSRIs) had longer PEP than controls. Longitudinal results confirmed these findings: compared with 2-year change in PEP in continuous non-users (+2 ms), subjects who started TCA or SNRI treatment showed significantly shortened PEP (-11 ms, p=0.005 and pantidepressant use. These findings suggest that depressive and anxiety disorders are not associated with increased cardiac sympathetic control. However, results pose

  13. Asymmetric Synthesis of Functionalized Tricyclic Chromanes via an Organocatalytic Triple Domino Reaction.

    Science.gov (United States)

    Kumar, Mukesh; Chauhan, Pankaj; Valkonen, Arto; Rissanen, Kari; Enders, Dieter

    2017-06-02

    A highly stereoselective triple domino reaction for the synthesis of functionalized tricyclic chromane scaffolds has been developed. A secondary amine-catalyzed domino Michael/Michael/aldol condensation reaction between aliphatic aldehydes, nitro-chromenes, and α,β-unsaturated aldehydes leads to the formation of synthetically important tricyclic chromanes bearing four contiguous stereogenic centers including a tetrasubstituted carbon in good yields (20-66%) and excellent stereoselectivities (>20:1 dr and >99% ee).

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

    Science.gov (United States)

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

    2015-06-01

    review. The two authors compared the data extracted and then entered data into RevMan 5 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by The Cochrane Collaboration. We retrieved a total of nine studies (861 participants), with seven studies contributing to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants and one-three armed study compared two antidepressants and a placebo arm. For the acute phase treatment response (6 to 12 weeks), we found very low quality evidence for the effect of antidepressants as a class on symptoms of depression compared with placebo when measured as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants) or as a proportion of people who had depression (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants). No trials reported data on the follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, providing very low quality evidence for the difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants). No clear evidence of an effect of antidepressants versus either placebo or other antidepressants emerged from the analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low quality evidence). We found very low quality evidence for the effect of antidepressants as a class in terms of dropouts due to any cause compared with placebo (RR 0.87, 95% CI 0.49 to 1.53, six RCTs, 455 participants), as well as between SSRIs and tricyclic antidepressants (RR 0

  15. Ergonomic Analysis of Tricycle Sidecar Seats: Basis for Proposed Standard Design

    Directory of Open Access Journals (Sweden)

    Michael C. Godoy

    2015-12-01

    Full Text Available Ergonomics (also called human factors engineering is the study of human characteristics for the appropriate design of the living and work environment. It is applied in various industrial areas which includes transportation.Tricycle being one of the most common means of public transportation in Lipa City has various adaptations to suit the culture, and environment. The purpose of this study is to analyze the variability in design of the tricycles in Lipa City, Philippines and propose a standard ergonomically designed tricycle sidecar seat for a greater population. The study was conducted at 26 tricycle terminals with 232 tricycle samples within Lipa City proper including the public market area where 400 commuters were given questionnaires to determine the risk factors associated with the existing tricycle sidecar seat design. Anthropometric measurements of 100 males and 100 female commuters were obtained together with the sidecar dimensions of 232 tricycles to substantiate the observed variations in design. Using the design for the average and design for the extremes, it was found out that most of the tricycles in Lipa City, Philippines have inappropriate inclined seat and lowered sidecar seat pan height which can result to leg and abdominal pain; narrowed seat pan depth which caused pressure on buttocks and legs; narrowed backrest width which can cause upper and low back pain; low backrest height that can pose upper back pain; which can also result to abdominal pain; inclined backrest and limited vertical clearance which can cause upper back pain and neck pain. The researcher proposed a sidecar seat design standard which can be used by the Land Transportation Office, and Land Transportation Franchising and Regulatory Board to provide ease, comfort, and convenience to the passengers.

  16. Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder.

    Science.gov (United States)

    Braun, Cora; Bschor, Tom; Franklin, Jeremy; Baethge, Christopher

    It is unclear whether antidepressants can prevent suicides or suicide attempts, particularly during long-term use. We carried out a comprehensive review of long-term studies of antidepressants (relapse prevention). Sources were obtained from 5 review articles and by searches of MEDLINE, PubMed Central and a hand search of bibliographies. We meta-analyzed placebo-controlled antidepressant RCTs of at least 3 months' duration and calculated suicide and suicide attempt incidence rates, incidence rate ratios and Peto odds ratios (ORs). Out of 807 studies screened 29 were included, covering 6,934 patients (5,529 patient-years). In total, 1.45 suicides and 2.76 suicide attempts per 1,000 patient-years were reported. Seven out of 8 suicides and 13 out of 14 suicide attempts occurred in antidepressant arms, resulting in incidence rate ratios of 5.03 (0.78-114.1; p = 0.102) for suicides and of 9.02 (1.58-193.6; p = 0.007) for suicide attempts. Peto ORs were 2.6 (0.6-11.2; nonsignificant) and 3.4 (1.1-11.0; p = 0.04), respectively. Dropouts due to unknown reasons were similar in the antidepressant and placebo arms (9.6 vs. 9.9%). The majority of suicides and suicide attempts originated from 1 study, accounting for a fifth of all patient-years in this meta-analysis. Leaving out this study resulted in a nonsignificant incidence rate ratio for suicide attempts of 3.83 (0.53-91.01). Therapists should be aware of the lack of proof from RCTs that antidepressants prevent suicides and suicide attempts. We cannot conclude with certainty whether antidepressants increase the risk for suicide or suicide attempts. Researchers must report all suicides and suicide attempts in RCTs. © 2016 S. Karger AG, Basel.

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

    Science.gov (United States)

    2014-08-01

    in culture at the drug concentrations used ( Fig. 1C ; Supplementary Fig. S1B; and data not shown) or in the lung epithelium of mice treated daily...SUPPLEMENTARY NOTES 14. ABSTRACT Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We...SCLC, small cell lung cancer, tri-cyclic anti-depressants, tricycl 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

  18. Switching antidepressants

    African Journals Online (AJOL)

    by this time.4. Next-step ... and the side-effects are minimal), switching to an alternative antidepressant (if .... the new SSRI initiated immediately at the former therapeutic equivalent dose ... weeks because of the long half-life of its active metabolite, .... interactions with second-generation antidepressants: an update. Clin Ther.

  19. Increased use of antidepressants and decreasing suicide rates

    DEFF Research Database (Denmark)

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

    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 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......), selective serotonin reuptake inhibitors (SSRI), other antidepressants). The change in the suicide rate during 1996-2000 was decomposed by treatment group. RESULTS: Only one in five older adults dying by suicide was in treatment at the time of death. Whereas the male suicide rate declined by 9.7 suicides per...

  20. 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.

  1. [Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and so on].

    Science.gov (United States)

    Sato, Mitsuko; Murakami, Masato

    2006-08-01

    Irritable bowel syndrome (IBS) is a functional disease with good prognosis, which is diagnosed by exclusion of possible causative organic diseases. However, since the patients tend to have strong psychotic symptoms including anxiety, tension, depression, irritation and insomnia, this syndrome has to be elucidated as a psychosomatic disease. Although the symptoms are usually limited to gastrointestinal symptoms such as abdominal pain and abnormal bowel movements, many patients also manifest some kinds of psychiatric abnormalities such as hypochondria, depression, hysteria, panic disorder and posttraumatic stress disorder. Especially, the prevalence of depression is high. Therefore, use of psychotropic drugs is efficient in treating IBS. Antidepressant agents including tricyclic agents such as amitriptyline, trimipramine, imipramine, clomipramine, amoxapine and nortriptyline; tetracyclic antidepressant; antidepressants such as SSRI and SNRI; sulpiride; benzodiazepine class anxiolytic agents; tandospirone; and Chinese herbal medicine are being used. IBS is a stress-related disease. Therefore, in spite of the importance of pharmacotherapy, patients should also be instructed to avoid the stress that aggravates the symptoms in all aspects of daily life.

  2. 抗抑郁药在皮肤科应用的研究进展%Application of antidepressants in dermatology

    Institute of Scientific and Technical Information of China (English)

    杨华; 马鹏程

    2015-01-01

    Besides antidepressant effect,some antidepressants also have sedative,antinociceptive and antihistamine effects,and have been used for the treatment of various dermatoses.Tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants.The diseases that can be treated by antidepressants include primary psychiatric disorders,dermatoses related to stress or emotion,cutaneous sensory disorders and mental status-unrelated dermatoses.These drugs have shown good therapeutic effects,few adverse effects,and are of great value for the improvement of patients' quality of life.%抗抑郁药能改善患者抑郁的情绪障碍,部分药物还具有镇静、镇痛及抗组胺作用,目前已用于治疗各种皮肤病.其中三环类抗抑郁药及选择性5羟色胺再摄取抑制剂应用最广泛,治疗的相关疾病包括原发的精神性疾病、与情绪或压力相关的皮肤病、纯粹的感觉障碍及与精神状态无关的皮肤病.其疗效好,不良反应相对较小,对提高患者的生活质量具有重要意义.

  3. 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.

  4. 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.

  5. Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control: A Longitudinal Study

    Science.gov (United States)

    Licht, Carmilla M M; Penninx, Brenda W J H; de Geus, Eco J C

    2012-01-01

    Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of antidepressant medication. The aim of this study was to test longitudinally whether cardiac sympathetic control, measured by pre-ejection period (PEP), was increased by depression/anxiety status and by antidepressant use. Cross-sectional and longitudinal data were from a depression and anxiety cohort: the Netherlands Study of Depression and Anxiety (NESDA). Baseline data of 2838 NESDA subjects (mean age 41.7 years, 66.7% female) and 2-year follow-up data of 2226 subjects were available for analyses. Included were subjects with and without depressive/anxiety disorders, using or not using different antidepressants at baseline or follow-up. The PEP was measured non-invasively by 1.5 h of ambulatory impedance cardiography. Cross-sectional analyses compared PEP across psychopathology and antidepressant groups. Longitudinal analyses compared 2-year changes in PEP in relation to changes in psychopathology and antidepressant use. Cross-sectional analyses showed that antidepressant-naïve depressive/anxious subjects had comparable PEP as controls, whereas subjects using tricyclic (TCA) or combined serotonergic/noradrenergic antidepressants (SNRI) had significantly shorter PEP compared with controls. In contrast, subjects using selective serotonin re-uptake inhibitors (SSRIs) had longer PEP than controls. Longitudinal results confirmed these findings: compared with 2-year change in PEP in continuous non-users (+2 ms), subjects who started TCA or SNRI treatment showed significantly shortened PEP (−11 ms, p=0.005 and p<0.001), whereas subjects who started SSRI treatment showed significant prolongation of PEP (+9 ms, p=0.002). Reversed findings were observed among those who

  6. IC Treatment: Antidepressants

    Science.gov (United States)

    ... restrictions than MAOIs. Studies Testing Antidepressants to Treat IC With the exception of the TCA called amitriptyline ( ... when you have IC). Antidepressants Used to Treat IC Some of the current antidepressants your physician may ...

  7. Mortality in major affective disorder: relationship to subtype of depression. The Danish University Antidepressant Group

    DEFF Research Database (Denmark)

    Buchholtz-Hansen, P E; Wang, A G; Kragh-Sørensen, P

    1993-01-01

    of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of > or = 18 and/or a Hamilton subscale score of > or = 9. Diagnostic classification...... a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk in the first 3 years...

  8. Rising Trend of Use of Antidepressants Induced Non- Puerperal Lactation: A Case Report

    Science.gov (United States)

    Ali, Wazid; Jiloha, R.C.

    2016-01-01

    Non puerperal lactation or galactorrhea is a well known side effect of antipsychotic drugs but has been infrequently described with the use of antidepressants. In past few decades, there have been emerging trend of isolated case reports of selective serotonin reuptake inhibitors induced non puerperal lactation. We report a case of non puerperal lactation following usage of second generation tricyclic antidepressant, nortriptyline and resolution on withdrawing the drug. Literature review has been done for antidepressant induced galactorrhea to understand the current trends, putative mechanism as different from one implicated for antipsychotics and its clinical utility. PMID:27504388

  9. 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.

  10. Neuropeptidomics of mouse hypothalamus after imipramine treatment reveal somatostatin as a potential mediator of antidepressant effects.

    Science.gov (United States)

    Nilsson, Anna; Stroth, Nikolas; Zhang, Xiaoqun; Qi, Hongshi; Fälth, Maria; Sköld, Karl; Hoyer, Daniel; Andrén, Per E; Svenningsson, Per

    2012-01-01

    Excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with numerous diseases, including depression, and the tricyclic antidepressant imipramine has been shown to suppress activity of the HPA axis. Central hypothalamic control of the HPA axis is complex and involves a number of neuropeptides released from multiple hypothalamic subnuclei. The present study was therefore designed to determine the effects of imipramine administration on the mouse hypothalamus using a peptidomics approach. Among the factors found to be downregulated after acute (one day) or chronic (21 days) imipramine administration were peptides derived from secretogranin 1 (chromogranin B) as well as peptides derived from cerebellin precursors. In contrast, peptides SRIF-14 and SRIF-28 (1-11) derived from somatostatin (SRIF, somatotropin release inhibiting factor) were significantly upregulated by imipramine in the hypothalamus. Because diminished SRIF levels have long been known to occur in depression, a second part of the study investigated the roles of individual SRIF receptors in mediating potential antidepressant effects. SRA880, an antagonist of the somatostatin-1 autoreceptor (sst1) which positively modulates release of endogenous SRIF, was found to synergize with imipramine in causing antidepressant-like effects in the tail suspension test. Furthermore, chronic co-administration of SRA880 and imipramine synergistically increased BDNF mRNA expression in the cerebral cortex. Application of SRIF or L054264, an sst2 receptor agonist, but not L803807, an sst4 receptor agonist, increased phosphorylation of CaMKII and GluR1 in cerebrocortical slices. Our present experiments thus provide evidence for antidepressant-induced upregulation of SRIF in the brain, and strengthen the notion that augmented SRIF expression and signaling may counter depressive-like symptoms. This article is part of a Special Issue entitled 'Anxiety and Depression'.

  11. Parasomnias and antidepressant therapy: a review of the literature.

    Science.gov (United States)

    Kierlin, Lara; Littner, Michael R

    2011-01-01

    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 REM sleep behavior disorder 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 selective serotonin reuptake inhibitors, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors to suppress REM, as well as the anticholinergic properties of the individual drugs to further disturb normal sleep architecture.

  12. Preferential reduction of binding of sup 125 I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments

    Energy Technology Data Exchange (ETDEWEB)

    Ordway, G.A.; Gambarana, C.; Tejani-Butt, S.M.; Areso, P.; Hauptmann, M.; Frazer, A. (Veterans Affairs Medical Center, Philadelphia, PA (USA))

    1991-05-01

    This study utilized quantitative receptor autoradiography to examine the effects of repeated administration of antidepressants to rats on the binding of the beta adrenoceptor antagonist, {sup 125}I-iodopindolol ({sup 125}I-IPIN) to either beta-1 or beta-2 adrenoceptors in various regions of brain. Antidepressants were selected to represent various chemical and pharmacological classes including tricyclic compounds (desipramine and protriptyline), monoamine oxidase inhibitors (clorgyline, phenelzine and tranylcypromine), atypical antidepressants (mianserin and trazodone) and selective inhibitors of the uptake of serotonin (citalopram and sertraline). Additionally, rats were treated with various psychotropic drugs that lack antidepressant efficacy (cocaine, deprenyl, diazepam and haloperidol). Repeated treatment of rats with desipramine, protriptyline, clorgyline, phenelzine, tranylcypromine or mianserin reduced the binding of {sup 125}I-IPIN to beta-1 adrenoceptors in many brain areas. Only in the basolateral and lateral nuclei of the amygdala did all six of these antidepressants significantly reduce {sup 125}I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of {sup 125}I-IPIN caused by each of these drugs was comparable to or greater than the reduction in binding produced in any other region of brain. Reductions of binding of {sup 125}I-IPIN after antidepressant treatments were not consistently observed in the cortex, the area of brain examined most often in homogenate binding studies. Only the monoamine oxidase inhibitors caused reductions in the binding of {sup 125}I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus.

  13. Duloxetine versus other anti-depressive agents for depression

    Science.gov (United States)

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

    2014-01-01

    versus escitalopram and two versus fluoxetine), four studies (overall 1978 participants) comparing duloxetine with a newer antidepressants (three with venlafaxine and one with desvenlafaxine, respectively) and one study (overall 453 participants) comparing duloxetine with an antipsychotic drug which is also used as an antidepressive agent, quetiapine. No studies were found comparing duloxetine with tricyclic antidepressants. The pooled confidence intervals were rather wide and there were no statistically significant differences in efficacy when comparing duloxetine with other antidepressants. However, when compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively). There was also some weak evidence suggesting that patients taking duloxetine experienced more adverse events than paroxetine (OR 1.24; 95% CI 0.99 to 1.55). Authors’ conclusions Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability. Unfortunately, we only found evidence comparing duloxetine with a handful of other active antidepressive agents and only a few trials per comparison were found (in some cases we retrieved just one trial). This limited the power of the review to detect moderate, but clinically meaningful differences between the drugs. As many statistical tests have been used in the review, the findings from this review are better thought of as hypothesis forming rather than hypothesis testing and it would be very comforting to see the conclusions replicated in future trials. Most of included studies

  14. 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

  15. The effects of antidepressants in Parkinson's disease: a meta-analysis.

    Science.gov (United States)

    Frisina, Pasquale G; Tenenbaum, Harriet R; Borod, Joan C; Foldi, Nancy S

    2008-05-01

    This study explored the therapeutic effect of antidepressants in Parkinson's disease (PD) using a meta-analysis. Altogether, 24 placebo-controlled trials qualified for inclusion and revealed that tricyclic antidepressants (TCAs) had a greater antidepressant effect relative to selective serotonin reuptake inhibitors (SSRIs), Qb(1) = 8.87, p < .01, and the mono-amine-oxidase inhibitor, selegiline, Qb(1) = 7.90, p < .01. Whereas TCAs produced a significant side effect profile (odds ratio = 3.07), adverse events were negligible with SSRIs (odds ratio = 1.83) and selegeline (odds ratio = 1.63). Antidepressants can be beneficial for patients with PD. However, the choice of antidepressants needs to take depressive symptomatologies into account while monitoring side effects.

  16. Design and Implementation of A PV Powered Tri-Cycle

    Directory of Open Access Journals (Sweden)

    Soumya Das

    2016-04-01

    Full Text Available Solar PV technology is one of the first among the various renewable energy technologies that have been adopted and accepted universally in order to meet the basic needs of generation of electricity. The objective of this paper is to propose a tri-cycle that utilises the application of stand-alone photovoltaic (PV system. A preliminary design and construction of a solar tri-cycle has been performed by evaluating and estimating the required panel size, battery capacity and motor power. Calculation in this paper exhibit that the solar power alone will be sufficient to operate a tri-cycle from one place to another.

  17. Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics.

    Science.gov (United States)

    Vestergaard, Peter

    2008-09-01

    Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

  18. Estudo das alterações eletrocardiográficas com o uso de antidepressivos tricíclicos em pacientes com dor crônica Estudio de las alteraciones electrocardiográficas con el uso de antidepresivos tricíclicos en pacientes con dolor crónico A study on electrocardiographic changes secondary to the use of tricyclic antidepressants in patients with chronic pain

    Directory of Open Access Journals (Sweden)

    Ricardo Joaquim da Cunha Jr.

    2009-02-01

    TODO: Se estudiaron 40 pacientes con edad entre 26 y 81 años (m = 57,27 ± 13,65 años, de los dos sexos (mujeres 19, hombres 21, con síndromes neuropáticos (lumbociatalgias, síndromes pos-laminectomía, neuritis pos-herpética, entre otras; un 60% con enfermedades cardiovasculares; 30% tenían ECG alterado (BRD, BRE, BAV 1°G, HBAE o extra-sístoles. Se realizaron y se analizaron tres ECGs: antes del inicio de los ADT, 30 y 60 días después del inicio del tratamiento, evaluando los parámetros PR, QRS, QT, QTc, DQT, DQTc y FC. Treinta y dos pacientes usaron amitriptilina y ocho imipramina. La dosis promedio al final del estudio fue de 54,29 mg de amitriptilina y de 46,87 mg de imipramina. RESULTADOS: El análisis de las variables electrocardiográficas después del uso de los ADT arrojó lo siguiente: la amitriptilina aumentó la frecuencia cardíaca transitoriamente en el sexo femenino (p = 0,049 y la duración del QRS en los pacientes con edad igual o superior a los 60 años y en los cardiópatas en la segunda evaluación (p = 0,01. En los pacientes que recibieron amitriptilina, dosis de 75 mg, el intervalo QTc fue mayor cuando se le comparó a las dosis de 25 mg (p = 0,0044. El aumento de esos parámetros mostró el efecto de la amitriptilina sobre la conducción cardíaca, sin embargo, no se registró comprometimiento clínico, pues los valores permanecieron dentro de los límites de la normalidad (QRS BACKGROUND AND OBJECTIVES: Tricyclic antidepressants (TCAs are widely used as analgesics in chronic lumbar pain and neuropathic pain. The objective of this study was to evaluate the electrocardiographic changes in patients with chronic pain treated with amitriptyline or imipramine. METHODS: Forty patients, ages 26 to 81 years (57.27 ± 13.65 years of both genders (female 19, male 21, with neuropathic syndromes (lumbosciatalgia, postlaminectomy syndromes, and post-herpetic neuritis, among others participated in this study; 60% had cardiovascular diseases; 30% had

  19. Effect of tricyclic drugs on mitochondrial membrane.

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    Eto,Kohei

    1985-08-01

    Full Text Available The effects of tricyclic drugs (clomipramine, imipramine, chlorpromazine and promethazine on isolated liver mitochondria of rats were examined. All the drugs tested accelerated state 4 respiration. Their stimulative potency at concentrations below 100 microM was in the order of chlorpromazine greater than clomipramine greater than imipramine, promethazine. On state 3 respiration, the chlorine containing drugs had an inhibitive effect at high concentrations, while the other drugs seemed to have a slightly stimulative effect. These drugs stimulated latent ATPase activity of mitochondria. Clomipramine and chlorpromazine inhibited 2, 4-dinitrophenol-stimulated ATPase activity in a dose-dependent fashion. Imipramine also inhibited 2, 4-dinitrophenol-stimulated ATPase activity at high concentrations. Promethazine, however, had almost no effect. All the drugs induced potassium release from mitochondrial vesicles, and their potency was in the order of clomipramine greater than chlorpromazine greater than imipramine greater than promethazine. These results suggest that clomipramine, imipramine, chlorpromazine and promethazine cause impediments in both mitochondrial respiration and ion compartmentation, and that the chlorine containing drugs are more toxic than others on the functions of the mitochondrial membrane.

  20. Antidepressants and Valvular Heart Disease: A Nested Case-Control Study in Taiwan.

    Science.gov (United States)

    Lin, Chia-Hui; Hsiao, Fei-Yuan; Liu, Yen-Bin; Gau, Susan Shur-Fen; Wang, Chi-Chuan; Shen, Li-Jiuan

    2016-04-01

    Empirical evidence regarding the association between antidepressants and valvular heart disease (VHD) is scarce.Using Taiwan's National Health Insurance Research database, this nested case-control study assessed the association between antidepressants and VHD in a Chinese population.Among a cohort of patients who used at least 3 prescription antidepressants, 874 cases with VHD and 3496 matched controls (1:4 ratio) were identified. Conditional logistic regression models were used to examine the timing, duration, dose and type of antidepressants use, and the risk of VHD.Current use of antidepressants was associated with a 1.4-fold increase in the risk of VHD (adjusted odds ratio [aOR] 1.44; 95% confidence interval [CI] 1.17-1.77). Among current users, a dose-response association was observed in terms of the cumulative duration and the cumulative antidepressant dose. Significantly higher risks of VHD were observed among the current users of tricyclic antidepressants (aOR 1.40 [1.05-1.87]).We found that the use of antidepressants was associated with a greater risk of VHD and that the risks varied according to different antidepressants.

  1. Antidepressants and dementia

    DEFF Research Database (Denmark)

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

    2009-01-01

    -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......BACKGROUND: It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. METHOD: Linkage of registers of all prescribed antidepressants and diagnoses of dementia...... the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non...

  2. IC Treatment: Antidepressants

    Science.gov (United States)

    ... such as fibromyalgia , irritable bowel syndrome , depression and anxiety, or attention deficit/hyperactivity disorder (ADHD). Some doctors also prescribe antidepressants to help cigarette smokers quit. Types of Antidepressants ...

  3. Evaluations of the Absolute and Relative Free Energies for Antidepressant Binding to the Amino Acid Membrane Transporter LeuT with Free Energy Simulations.

    Science.gov (United States)

    Zhao, Chunfeng; Caplan, David A; Noskov, Sergei Yu

    2010-06-08

    The binding of ligands to protein receptors with high affinity and specificity is central to many cellular processes. The quest for the development of computational models capable of accurately evaluating binding affinity remains one of the main goals of modern computational biophysics. In this work, free energy perturbation/molecular dynamics simulations were used to evaluate absolute and relative binding affinity for three different antidepressants to a sodium-dependent membrane transporter, LeuT, a bacterial homologue of human serotonin and dopamine transporters. Dysfunction of these membrane transporters in mammals has been implicated in multiple diseases of the nervous system, including bipolar disorder and depression. Furthermore, these proteins are key targets for antidepressants including fluoxetine (aka Prozac) and tricyclic antidepressants known to block transport activity. In addition to being clinically relevant, this system, where multiple crystal structures are readily available, represents an ideal testing ground for methods used to study the molecular mechanisms of ligand binding to membrane proteins. We discuss possible pitfalls and different levels of approximation required to evaluate binding affinity, such as the dependence of the computed affinities on the strength of constraints and the sensitivity of the computed affinities to the particular partial charges derived from restrained electrostatic potential fitting of quantum mechanics electrostatic potential. Finally, we compare the effects of different constraint schemes on the absolute and relative binding affinities obtained from free energy simulations.

  4. CNS effects of citalopram, a new serotonin inhibitor antidepressant (a quantitative pharmaco-electroencephalography study).

    Science.gov (United States)

    Itil, T M; Menon, G N; Bozak, M M; Itil, K Z

    1984-01-01

    Citalopram, a new phthalane derivative and a specific serotonin re-uptake inhibitor in animal pharmacological tests, was evaluated in a double-blind, crossover, quantitative pharmaco-EEG (QPEEGTM) study in healthy human volunteers. The CNS effects of citalopram are linear, dose- and time-related, can statistically be differentiated from placebo, and indicate a rapid onset of effects with short duration. According to the Computer Data Bank, citalopram has a mode of action similar to mood elevators (antidepressants) with fewer sedative properties. Thus the therapeutic action of citalopram is predicted to be similar to desipramine and protriptyline from the tricyclics, and fluvoxamine from non-tricyclics. According to data bank assessment, it is hypothesized that the single antidepressant dose of citalopram is to be more than 25 mg, which should be given t.i.d. in clinical trials.

  5. Structural basis for action by diverse antidepressants on biogenic amine transporters.

    Science.gov (United States)

    Wang, Hui; Goehring, April; Wang, Kevin H; Penmatsa, Aravind; Ressler, Ryan; Gouaux, Eric

    2013-11-07

    The biogenic amine transporters (BATs) regulate endogenous neurotransmitter concentrations and are targets for a broad range of therapeutic agents including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Because eukaryotic BATs are recalcitrant to crystallographic analysis, our understanding of the mechanism of these inhibitors and antidepressants is limited. LeuT is a bacterial homologue of BATs and has proven to be a valuable paradigm for understanding relationships between their structure and function. However, because only approximately 25% of the amino acid sequence of LeuT is in common with that of BATs, and as LeuT is a promiscuous amino acid transporter, it does not recapitulate the pharmacological properties of BATs. Indeed, SSRIs and TCAs bind in the extracellular vestibule of LeuT and act as non-competitive inhibitors of transport. By contrast, multiple studies demonstrate that both TCAs and SSRIs are competitive inhibitors for eukaryotic BATs and bind to the primary binding pocket. Here we engineered LeuT to harbour human BAT-like pharmacology by mutating key residues around the primary binding pocket. The final LeuBAT mutant binds the SSRI sertraline with a binding constant of 18 nM and displays high-affinity binding to a range of SSRIs, SNRIs and a TCA. We determined 12 crystal structures of LeuBAT in complex with four classes of antidepressants. The chemically diverse inhibitors have a remarkably similar mode of binding in which they straddle transmembrane helix (TM) 3, wedge between TM3/TM8 and TM1/TM6, and lock the transporter in a sodium- and chloride-bound outward-facing open conformation. Together, these studies define common and simple principles for the action of SSRIs, SNRIs and TCAs on BATs.

  6. Studies on antidepressant action of a new oxazolidinone derivative AS-8.

    Science.gov (United States)

    Kostowski, W; Płaźnik, A; Bidziński, A; Rosnowska, E; Jessa, M; Nazar, M

    1994-01-01

    On the basis of previous laboratory studies AS-8 was suggested to possess antidepressant-like activity. Forced swim test, learned helplessness and conflict Vogel's test were performed after three prior administrations of AS-8 (24, 5 and 1 h before the test). The data have shown that AS-8 produces moderate antidepressant effect but did not induce anxiolytic-like action. Biochemical data revealed increased brain 5-HT and 5-HIAA levels following AS-8 administration. The combined treatment of rats with AS-8 (100 mg/kg) and amitriptyline (5 mg/kg) or desipramine (1.25 mg/kg) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drug given separately. The present data suggest the potential antidepressant efficacy of AS-8 in conjunction with small doses of tricyclic antidepressants.

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

    Directory of Open Access Journals (Sweden)

    Harada T

    2014-11-01

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

  9. PHARMACOEPIDEMIOLOGICAL MONITORING OF ANTIDEPRESSANT USAGE IN PATIENTS WITH ANXIOUS AND DEPRESSIVE SYNDROMES IN INTERNAL MEDICINE

    Directory of Open Access Journals (Sweden)

    N. V. Ivanova

    2015-12-01

    Full Text Available Aim. To study antidepressant usage in treatment of anxious and depressive disorders in real internal medicine practice.Material and methods. Retrospective analysis of 290 charts of patients, which were observed in Pskov region hospital from 2004 to 2005 was held. All patients suffered from different internal diseases and were treated with antidepressants because of anxious and depressive concomitant disorders.Results. Arterial hypertension observed in 28% of patients, ischemic heart disease – in 20%, heart failure – in 14%, cerebrovascular and peripheral nervous system diseases – in 18% and gastroduodenal diseases – in 20% of patients. Amitriptyline took the first place (49% among antidepressant prescriptions. Next antidepressants according to prescription popularity were paroxetine (22% and tianeptine (12%. Rate of other antidepressant prescriptions were not higher than 5%. There were differences in antidepressant prescriptions between physicians of different specialties.Conclusion. Reasonable approaches should be used to choose antidepressants. Selective serotonin reuptake inhibitors have benefit for the therapy of concomitant anxious and depressive disorders due to their good tolerability. Nevertheless tricyclic antidepressants are essential in some clinical situations.

  10. PHARMACOEPIDEMIOLOGICAL MONITORING OF ANTIDEPRESSANT USAGE IN PATIENTS WITH ANXIOUS AND DEPRESSIVE SYNDROMES IN INTERNAL MEDICINE

    Directory of Open Access Journals (Sweden)

    N. V. Ivanova

    2007-01-01

    Full Text Available Aim. To study antidepressant usage in treatment of anxious and depressive disorders in real internal medicine practice.Material and methods. Retrospective analysis of 290 charts of patients, which were observed in Pskov region hospital from 2004 to 2005 was held. All patients suffered from different internal diseases and were treated with antidepressants because of anxious and depressive concomitant disorders.Results. Arterial hypertension observed in 28% of patients, ischemic heart disease – in 20%, heart failure – in 14%, cerebrovascular and peripheral nervous system diseases – in 18% and gastroduodenal diseases – in 20% of patients. Amitriptyline took the first place (49% among antidepressant prescriptions. Next antidepressants according to prescription popularity were paroxetine (22% and tianeptine (12%. Rate of other antidepressant prescriptions were not higher than 5%. There were differences in antidepressant prescriptions between physicians of different specialties.Conclusion. Reasonable approaches should be used to choose antidepressants. Selective serotonin reuptake inhibitors have benefit for the therapy of concomitant anxious and depressive disorders due to their good tolerability. Nevertheless tricyclic antidepressants are essential in some clinical situations.

  11. 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

  12. Inflammatory Biomarkers as Differential Predictors of Antidepressant Response

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    2015-04-01

    Full Text Available Although antidepressants are generally effective in the treatment of major depressive disorder (MDD, it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA receptor antagonist ketamine.

  13. Effects of tricyclic compounds and other drugs having a membrane stabilizing action on analgesia, tolerance to and dependence on morphine.

    Science.gov (United States)

    Contreras, E; Tamayo, L; Quijada, L

    1977-08-01

    Several drugs affecting nerve cell excitability, by opposing ion movements in membranes, were tested in mice rendered tolerant to or dependent on morphine. The purpose of the study was to investigate whether these drugs share the ability to attenuate morphine tolerance and dependence exhibited by tricyclic antidepressants. Tolerance to morphine was decreased by the administration of imipramine, doxepin, promethazine, propranolol, lidocaine and quinidine. Chlorpromazine and carbamazepine were ineffective. The intensity of the abstinence syndrome provoked by naloxone was decreased by chlorpromazine, imipramine, doxepin, lidocaine, quinidine and propranolol. Diphenyl. hydantion and carbamazepine had no effect. The results are discussed in relation with the blockade of ion conductance and their interference with the release of neurotransmitters produced by the drugs assayed.

  14. 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.

  15. 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.

  16. Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

    Science.gov (United States)

    Powell, Timothy R; Murphy, Tytus; Lee, Sang H; Price, Jack; Thuret, Sandrine; Breen, Gerome

    2017-01-01

    Current pharmacological treatments for major depressive disorder (MDD) are ineffective in a significant proportion of patients, and the identification of new antidepressant compounds has been difficult. ‘Connectivity mapping’ is a method that can be used to identify drugs that elicit similar downstream effects on mRNA levels when compared to current treatments, and thus may point towards possible repositioning opportunities. We investigated genome-wide transcriptomic changes to human hippocampal progenitor cells treated with therapeutically relevant concentrations of a tricyclic antidepressant (nortriptyline) and a selective serotonin reuptake inhibitor (escitalopram). We identified mRNA changes common to both drugs to create an ‘antidepressant mRNA signature’. We used this signature to probe the Library of Integrated Network-based Cellular Signatures (LINCS) and to identify other compounds that elicit similar changes to mRNA in neural progenitor cells. Results from LINCS revealed that the tricyclic antidepressant clomipramine elicited mRNA changes most similar to our mRNA signature, and we identified W-7 and vorinostat as functionally relevant drug candidates, which may have repositioning potential. Our results are encouraging and represent the first attempt to use connectivity mapping for drug repositioning in MDD. PMID:28208023

  17. Differing antidepressant maintenance methodologies.

    Science.gov (United States)

    Safer, Daniel J

    2017-10-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  19. 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.

  20. Vintage treatments for PTSD: a reconsideration of tricyclic drugs.

    Science.gov (United States)

    Davidson, Jonathan

    2015-03-01

    Serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors (SSRI) are the first-line recommended drug treatments for post-traumatic stress disorder (PTSD); but despite their benefits, much residual pathology remains and no new drugs have yet emerged with a clearly demonstrated benefit for treating the disorder. A case is made that tricyclic drugs deserve a closer look, based on their ability to affect several of the main neurotransmitters that are relevant to PTSD. Their promising efficacy, which was shown 30 years ago, had not been followed up, until a recent trial of desipramine found advantages over a SSRI in PTSD with comorbid alcohol dependence. Opportunities exist for studying newer and purportedly safer tricyclic formulations, as well as further the work with older, established compounds. A reappraisal of their risk:benefit ratio seems in order, when treating PTSD.

  1. 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

  2. Thermostabilization of the Human Serotonin Transporter in an Antidepressant-Bound Conformation.

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    Evan M Green

    Full Text Available Serotonin is a ubiquitous chemical transmitter with particularly important roles in the gastrointestinal, cardiovascular and central nervous systems. Modulation of serotonergic signaling occurs, in part, by uptake of the transmitter by the serotonin transporter (SERT. In the brain, SERT is the target for numerous antidepressants including tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs. Despite the importance of SERT in human physiology, biochemical, biophysical and high-resolution structural studies have been hampered due to the instability of SERT in detergent micelles. To identify a human SERT (hSERT construct suitable for detailed biochemical and structural studies, we developed an efficient thermostability screening protocol and rapidly screened 219 mutations for thermostabilization of hSERT in complex with the SSRI paroxetine. We discovered three mutations-Y110A, I291A and T439S -that, when combined into a single construct, deemed TS3, yielded a hSERT variant with an apparent melting temperature (Tm 19°C greater than that of the wild-type transporter, albeit with a loss of transport activity. Further investigation yielded a double mutant-I291A and T439S-defined as TS2, with a 12°C increase in Tm and retention of robust transport activity. Both TS2 and TS3 were more stable in short-chain detergents in comparison to the wild-type transporter. This thermostability screening protocol, as well as the specific hSERT variants, will prove useful in studies of other integral membrane receptors and transporters and in the investigation of structure and function relationships in hSERT.

  3. A Novel Approach to Synthesis of Tricyclic Diterpenoid

    Institute of Scientific and Technical Information of China (English)

    Peng Xuan-jia; She Xue-gong; Su Ying; Wu Tong-xin; Pan Xin-fu

    2004-01-01

    A novel approach has been found and the first total synthesis of (±)-Salvirecognine was accomplished by using it. In which intramolecular cyclization and Friedel-Crafts alkylation took place simultaneously to afford key intermediates for synthesis of aromatic tricyclic diterpenoids Scheme 1As shown in Scheme 1 intramolecular cyclization and Friedel-Crafts alkylation took place simultaneously when compound 1 was treated by PPA at 125 ℃. In which the i-propyl group was introduced to the benzene ring directly and 2 was obtained in high yield. The structure of 2 was confirmed by X-ray crystallographic analysis.Scheme 2The mechanism of this novel approach might be as shown in Scheme 2. It's may be involved two times Friedel-Crafts alkylation and once fragmentation. We tried several different substrates and the new method was not only applicable in the conventional [6.6.6] tricyclic compounds but also suitable in [6.5.6] tricyclic compounds.By using the new approach as shown in Scheme 3 the first total synthesis of Salvirecognine 4,isolated from salvia recognit was achieved.Reagents and conditions: i) PPA, 125℃, 90%; ii) BBr3, CH2Cl2, 85%; iii) AlCl2H, 95%;Scheme 3

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

    Science.gov (United States)

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

    2017-01-15

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

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

    Science.gov (United States)

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

    2016-12-01

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

  6. [Changes in antidepressants consumption in the health area of Zamora from 1996 to 1999].

    Science.gov (United States)

    Díaz Madero, A; López Ferreras, A; Ruiz-Clavijo Díez, M; Vargas Aragón, M

    2001-09-30

    To describe the evolution of antidepressants outside hospital consumption (therapeutic subgroup N06A) in the health area of Zamora since 1996 to 1999, and also to rate the impact of the most recently marketed drugs introduction. Retrospective observational study. Primary care. All antidepressants containers dispensed in Zamora with prescription of the Seguridad Social in the 1996-1999 period are obtained from SIFAR (Pharmacy Management Informatic System), computing defined daily doses per 1000 inhabitants day (DHD) for each drug. An increase of 47% in antidepressants whole consumption is observed, progressively since 1996 to 1999: 18.91 DHD (1996); 22.09 DHD (1997); 24.67 DHD (1998); 27.85 DHD (1999).ISRS (88%) and heterocyclics (56%) increase in this period, whereas IMAO (71%) and tricyclic antidepressants (14%) decrease. Antidepressant whole consumption experiments an outstanding increase in the area of Zamora. Recently marketed drugs utilisation increases as well, superseding classical antidepressants. The five most used drugs in 1999 were, in decreasing order, paroxetine, fluoxetine, sertraline, citalopram and venlafaxine. These last three ones got the most outstanding rise in the reviewed period.

  7. Antidepressants: Safe during Pregnancy?

    Science.gov (United States)

    ... you need to know about antidepressants and pregnancy. Pregnancy hormones were once thought to protect women from depression, but researchers now say this isn't true. In addition, pregnancy can trigger a range of emotions that make ...

  8. Antidepressants and Alcohol

    Science.gov (United States)

    ... Medication-FAQ/Can-I-drink-alcohol-while-taking-antidepressants. Accessed May 2, 2017. Back SE, et al. Treatment of co-occurring substance use disorder and anxiety-related disorders in adults. https://www.uptodate.com/ ...

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

    Directory of Open Access Journals (Sweden)

    D. S. Danilov

    2015-01-01

    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. 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

  11. Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

    Science.gov (United States)

    Mika, Joanna; Zychowska, Magdalena; Makuch, Wioletta; Rojewska, Ewelina; Przewlocka, Barbara

    2013-01-01

    The current knowledge of the pharmacological actions of the tricyclic antidepressants (TCAs) has slowly evolved through their over 40-year history. Chronic pain represents one of the most important public health problems, and antidepressants are an essential part of the therapeutic strategy in addition to classical analgesics. This article reviews the available evidence on the efficacy and safety of antidepressants in chronic pain conditions; namely, headaches, low back pain, fibromyalgia, cancer pain and especially neuropathic pain. TCAs are traditionally the main type of depression medication used to treat chronic pain. Recently, new antidepressants were introduced into clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs that are effective for chronic pain belong to the tetracyclic antidepressants (TeCAs) group (amoxapine, maprotiline), the serotonin and noradrenaline reuptake inhibitors (SNRIs) group (duloxetine, venlafaxine, milnacipran) and the atypical antidepressants group (bupropion, trazodone, mirtazapine, nefazodone). In this review, we present the available publications on TCAs (amitriptyline, doxepin, imipramine, desipramine, nortriptyline), TeCAs (amoxapine, maprotiline), selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, paroxetine), SNRIs (duloxetine, venlafaxine, milnacipran) and atypical antidepressants (bupropion) for the treatment of neuropathic pain. We also review analgesics acting as both opioid receptor agonists and also acting as aminergic reuptake inhibitors. Existing data are insufficient to conclude which of these new classes of antidepressants has the best clinical profile and will be the most effective in the treatment of neuropathic pain; in addition, a lower incidence of side effects should be considered. Increased experimental and translational research is a key for further improvement of the treatment of chronic pain with antidepressants. However

  12. Antidepressants: update on new agents and indications.

    Science.gov (United States)

    Ables, Adrienne Z; Baughman, Otis L

    2003-02-01

    A number of antidepressants have emerged in the U.S. market in the past two decades. Selective serotonin reuptake inhibitors have become the drugs of choice in the treatment of depression, and they are also effective in the treatment of obsessive-compulsive disorder, panic disorder, and social phobia. New indications for selective serotonin reuptake inhibitors include post-traumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. Extended-release venlafaxine has recently been approved by the U.S. Food and Drug Administration for the treatment of generalized anxiety disorder. Mirtazapine, which is unrelated to the selective serotonin reuptake inhibitors, is unique in its action--stimulating the release of norepinephrine and serotonin. The choice of antidepressant drug depends on the agent's pharmacologic profile, secondary actions, and tolerability. Sexual dysfunction related to the use of antidepressants may be addressed by reducing the dosage, switching to another agent, or adding another drug to overcome the sexual side effects. Augmentation with lithium or triiodothyronine may be useful in patients who are partially or totally resistant to antidepressant treatment. Finally, tapering antidepressant medication may help to avoid discontinuation syndrome or antidepressant withdrawal.

  13. Accelerated antidepressant response to lithium augmentation of imipramine

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    Rajiv Saini

    2016-01-01

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

  14. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States.

    Science.gov (United States)

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

    2013-08-21

    were similar with hdPS adjustment. Women with current exposure to serotonin reuptake inhibitors had an adjusted excess risk of 1.26% (0.90% to 1.62%), with a number needed to harm of 80, and for women with current exposure to non-serotonin reuptake inhibitors the excess risk was 1.03% (0.07% to 1.99%), with a number needed to harm of 97. For exposure to serotonin reuptake inhibitors the relative risk was 1.19 (1.03 to 1.38) for recent exposure and 0.93 (0.82 to 1.06) for past exposure; for non-serotonin reuptake inhibitors the figures were 1.17 (0.80 to 1.70) and 1.26 (1.00 to 1.59), respectively. Current exposure to selective serotonin reuptake inhibitor monotherapy was also associated with postpartum hemorrhage (1.42, 1.27 to 1.57), as was current serotonin norepinephrine (noradrenaline) reuptake inhibitor (1.90, 1.37 to 2.63) and tricyclic monotherapy (1.77, 0.90 to 3.47). All types of selective serotonin reuptake inhibitors available for analysis and venlafaxine, a serotonin norepinephrine reuptake inhibitor, were significantly associated with postpartum hemorrhage. Exposure to serotonin and non-serotonin reuptake inhibitors, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclics, close to the time of delivery was associated with a 1.4 to 1.9-fold increased risk for postpartum hemorrhage. While potential confounding by unmeasured factors cannot be ruled out, these findings suggest that patients treated with antidepressants during late pregnancy are more likely to experience postpartum hemorrhage.

  15. Stereoselective biodegradation of tricyclic terpanes in heavy oils from the Bolivar Coastal Fields, Venezuela

    Energy Technology Data Exchange (ETDEWEB)

    Alberdi, M. [Stanford University (United States). Dept. of Geological and Environmental Sciences; PDVSA-Intevep, Caracas (Venezuela); Moldowan, J.M.; Dahl, J.E. [Stanford University (United States). Dept. of Geological and Environmental Sciences; Peters, K.E. [Mobil Technology Co., Dallas, TX (United States)

    2001-07-01

    Gas chromatography-mass spectrometry (GC-MS) and GC-MS-MS analyses of heavy oils from Bolivar Coastal Fields (Lagunillas Field) show a complete set of demethylated tricyclic terpanes. As is the case for the 25-norhopanes, the demethylated tricyclics are probably formed in reservoirs by microbially-mediated removal of the methyl group from the C-10 position, generating putative 17-nor-tricyclic terpanes. Diastereomeric pairs of tricyclic terpanes are resolved above C{sub 24} due to resolution of 22S and 22R epimers, but the elution order of the 22S and 22R epimers is unknown. Early-eluting diastereomers (EE) predominate over late-eluting diastereomers (LE) (C{sub 25}-C{sub 29}) in the heavily degraded oils, indicating a stereoselective preference for the LE stereoisomers during biodegradation. Conversely, the LE diastereomers predominate over the EE diastereomers in the 17-nor tricyclic series (C{sub 24}-C{sub 28}), indicating that tricyclic terpanes and 17-nor-tricyclic terpanes are directly linked as precursors and products, respectively. A good correlation exists between the destruction of steranes and the demethylation of hopanes and tricyclic terpanes. This suggests that terpane demethylation occurs during sterane destruction and hopane demethylation, although the rate is slower, indicating that tricyclic terpanes are more resistant to biodegradation. (Author)

  16. Kadcotriones A-C: tricyclic triterpenoids from Kadsura coccinea.

    Science.gov (United States)

    Liang, Cheng-Qin; Shi, Yi-Ming; Li, Xing-Yao; Luo, Rong-Hua; Li, Yan; Zheng, Yong-Tang; Zhang, Hong-Bin; Xiao, Wei-Lie; Sun, Han-Dong

    2013-12-27

    Three new triterpenoids, kadcotriones A-C (1-3), together with the biogenetically related lanostane-type triterpenoid (4), were isolated from Kadsura coccinea. Compound 1 features a 12,14β-dimethyl 6/6/6-fused tricyclic skeleton, while 2 and 3 are characterized by a 6/6/5-ring system. Their structures were determined by NMR and electronic circular dichroism spectroscopic methods. Compounds 2 and 4 exhibited anti-HIV-1 activities with EC50 values of 30.29 and 54.81 μM, respectively.

  17. 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

  18. Expression of monoamine transporters, nitric oxide synthase 3 and neurotrophin genes in antidepressant-stimulated astrocytes

    Directory of Open Access Journals (Sweden)

    Sarah eKittel-Schneider

    2012-04-01

    Full Text Available Background: There is increasing evidence that glial cells play a role in the pathomechanisms of mood disorders and the mode of action of antidepressant drugs. Methods: To examine whether there is a direct effect on the expression of different genes encoding proteins that have been implicated in the pathophysiology of affective disorders, primary astrocyte cell cultures from rats were treated with two different antidepressant drugs, imipramine and escitalopram, and the mRNA expression of brain derived neurotrophic factor (Bdnf, serotonin transporter (5Htt, dopamine transporter (Dat and endothelial nitric oxide synthase (Nos3 was examined. Results: Stimulation of astroglial cell culture with imipramine, a tricyclic antidepressant, lead to a significant increase of the Bdnf mRNA level whereas treatment with escitalopram did not. In contrast, 5Htt was not differentially expressed after antidepressant treatment. Finally, neither Dat nor Nos3 mRNA expression was detected in cultured astrocytes. Conclusions: These data provide further evidence for a role of astroglial cells in the molecular mechanisms of action of antidepressants.

  19. Antidepressant medications and osteoporosis

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  20. Nitric Oxide Synthase Inhibitors as Antidepressants

    Directory of Open Access Journals (Sweden)

    Vallo Volke

    2010-01-01

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

  1. The quetiapine active metabolite N-desalkylquetiapine and the neurotensin NTS₁ receptor agonist PD149163 exhibit antidepressant-like effects on operant responding in male rats.

    Science.gov (United States)

    Hillhouse, Todd M; Shankland, Zachary; Matazel, Katelin S; Keiser, Ashley A; Prus, Adam J

    2014-12-01

    Major depressive disorder is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that is apparent after 1 week of treatment, and it is possible that the active metabolite N-desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS1 receptor agonist PD149163 suggest antidepressant efficacy, but the effects of a NTS₁ receptor agonist in an antidepressant animal model have yet to be reported. The present study examined the antidepressant-like effects of N-desalkylquetiapine, PD14916, quetiapine, the tricyclic antidepressant drug imipramine, the atypical antipsychotic drug risperidone, and the typical antipsychotic drug raclopride on responding in male Sprague-Dawley rats trained on a differential-reinforcement-of-low-rate 72-s operant schedule, a procedure used for screening antidepressant drugs. Quetiapine, PD149163, risperidone, and imipramine exhibited antidepressant-like effects by increasing the number of reinforcers earned, decreasing the number of responses emitted, and shifting the interresponse time (IRT) distributions to the right. N-Desalkylquetiapine produced a partial antidepressant-like effect by decreasing the number of responses emitted and producing a rightward shift in the IRT distributions, but it did not significantly alter the number of reinforcers earned. Raclopride decreased reinforcers and responses. These data suggest that N-desalkylquetiapine likely contributes to quetiapine's antidepressant efficacy and identify NTS₁ receptor activation as a potential novel pharmacologic strategy for antidepressant drugs.

  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. LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake.

    Science.gov (United States)

    Zhou, Zheng; Zhen, Juan; Karpowich, Nathan K; Goetz, Regina M; Law, Christopher J; Reith, Maarten E A; Wang, Da-Neng

    2007-09-07

    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.

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

    DEFF Research Database (Denmark)

    Mao, Yanyan; Pedersen, Lars Henning; Christensen, Jakob;

    2016-01-01

    PURPOSE: This study aimed to estimate the association between prenatal exposure to antidepressants and risk of epilepsy in childhood, taking maternal depression into account. METHODS: We conducted a population-based cohort study including all Danish singletons born alive between 1997 and 2008 (n...... = 734 237). Information on antidepressant medication and diagnosis of depression and epilepsy was obtained from Danish National Registers. The exposed group comprised children of mothers who used antidepressants from 30 days before pregnancy until the date of birth. The reference group comprised...... children of mothers who used no antidepressants from 6 months before pregnancy to birth. We estimated the hazard ratios (HR) of epilepsy and 95% confidence intervals (CI) using Cox proportional hazard models. RESULTS: We identified 12 438 (1.7%) children exposed to antidepressants during pregnancy...

  5. Clinical implications of antidepressant drug effects on sexual function.

    Science.gov (United States)

    Harvey, K V; Balon, R

    1995-12-01

    Sexual dysfunction in a patient being treated with antidepressant medications may be due to the underlying depression, a coexisting medical illness, disruption of interpersonal relationships, or it may be a side effect of the medication. Almost all antidepressants are associated with sexual side effects that go above and beyond any symptoms that can be explained by the disease process itself. The incidence of such sexual side effects can be as high as 92% for some antidepressants. Some of the newer antidepressants currently on the market seem to have a lower incidence of sexual dysfunction as a side effect. In view of the fairly common occurrence of these unwanted effects, and their potential contribution to noncompliance, careful selection of antidepressant medications is necessary. A variety of treatment options is available, including decreasing the dosage of medication to the lowest-effective level, adjunctive medications (such as cyproheptadine, bethanechol, yohimbine, and amantadine, as well as other antidepressants) to counteract the adverse sexual effects, or switching to another antidepressant. The treatment of antidepressant-induced sexual dysfunction requires a creative approach on the part of the treating psychiatrist, and must be individualized to the patient.

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

    Science.gov (United States)

    Arantes-Gonçalves, Filipe; Coelho, Rui

    2006-01-01

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

  7. Antidepressants for people with epilepsy and depression.

    Science.gov (United States)

    Maguire, Melissa J; Weston, Jennifer; Singh, Jasvinder; Marson, Anthony G

    2014-12-03

    Depressive disorders are the most common psychiatric comorbidity in patients with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that patients may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best and the perceived risk of exacerbating seizures. This review aims to address these issues and inform clinical practice and future research. We aimed to review and synthesise evidence from randomised controlled trials of antidepressants and prospective non-randomised studies of antidepressants used for treating depression in patients with epilepsy. The primary objectives were to evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence. We conducted a search of the following databases: the Cochrane Epilepsy Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 5), MEDLINE (Ovid), SCOPUS, PsycINFO, www.clinicaltrials.gov and conference proceedings, including studies published up to 31 May 2014. There were no language restrictions. We included randomised controlled trials (RCTs) and prospective non-randomised cohort controlled and uncontrolled studies investigating children or adults with epilepsy treated with an antidepressant for depressive symptoms. The intervention group consisted of patients receiving an antidepressant drug in addition to an existing antiepileptic drug regimen. The control group(s) consisted of patients receiving a placebo, comparative antidepressant, psychotherapy or no treatment in addition to an existing antiepileptic drug regimen. We extracted data on trial design factors, patient demographics and outcomes for each study. The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement or mean difference) and change in seizure frequency (mean difference or

  8. Antidepressant drugs and breastfeeding: a review of the literature.

    Science.gov (United States)

    Davanzo, Riccardo; Copertino, Marco; De Cunto, Angela; Minen, Federico; Amaddeo, Alessandro

    2011-04-01

    The use of antidepressants in breastfeeding mothers is controversial: Manufacters often routinely discourage breastfeeding for the nursing mother despite the well-known positive impact that breastfeeding carries on the health of the nursing infant and on his or her family and society. We conducted a systematic review of drugs commonly used in the treatment of postpartum depression. For every single drug two sets of data were provided: (1) selected pharmacokinetic characteristics such as half-life, milk-to-plasma ratio, protein binding, and oral bioavailability and (2) information about lactational risk, according to some authoritative sources of the literature: Drugs in Pregnancy and Lactation edited by Briggs et al. (Lippincott Williams, Philadelphia, 2008), Medications and Mothers' Milk by Hale (Hale Publishing, Amarillo, TX, 2010), and the LactMed database of TOXNET ( www.pubmed.gov ; accessed June 2010). Notwithstanding a certain variability of advice, we found that (1) knowledge of pharmacokinetic characteristics are scarcely useful to assess safety and (2) the majority of antidepressants are not usually contraindicated: (a) Selective serotinin reuptake inhibitors and nortryptiline have a better safety profile during lactation, (b) fluoxetine must be used carefully, (c) the tricyclic doxepine and the atypical nefazodone should better be avoided, and (d) lithium, usually considered as contraindicated, has been recently rehabilitated.

  9. Synthesis and Thermal Behavior of a Fused, Tricyclic 1,2,3,4-Tetrazine Ring System.

    Science.gov (United States)

    Chavez, David E; Bottaro, Jeffery C; Petrie, Mark; Parrish, Damon A

    2015-10-26

    This study presents the synthesis and characterization of a fused, tricyclic 1,2,3,4-tetrazine ring system. The molecule is synthesized in a three-step process from 5,5'-dinitro-bis,1,2,4-triazole via a di-N-amino compound. Oxidation to form the azo-coupled fused tricyclic 1,2,3,4-tetrazine is achieved using tert-butyl hypochlorite as the oxidant. The di-N-amino compound and the desired fused tricyclic 1,2,3,4-triazine display interesting thermal behavior and are predicted to be high-performance energetic materials.

  10. Antidepressants administration in rheumatoid arthritiswith comorbid depression

    Directory of Open Access Journals (Sweden)

    N V Yaltseva

    2009-01-01

    Full Text Available Objective. To study comorbid depression influence on course of rheumatoid arthritis (RAand antidepressants efficacy in such pts. Material and methods. 70 pts with RA (all women fulfilled the 1987 ACR criteria with comorbid depression disturbances were included. 30 from them received course of treatment with antidepressants (main group. 20 refused proposed therapy (main control group. 20 RA pts without depression were included in an additional control group which was also followed up. Hamilton scales of depression and anxiety were used. Results. Baseline clinical measures did not significantly differ between study groups. Antidepressants application in main group pts was accompanied by significant improvement of tender and swollen joint count, morning stiffness duration, pain intensity (score,functional disability index (FDI after 3 months (<0,001,<0,001, <0,01, <0,001,<0,001. This improvement further increased to sixth month of follow up. Comparison of main and additional control groups showed better outcome in the absence of comorbid depression and its negative influence on results of treatment. Conclusion. Effective treatment of depression with modern antidepressants (selective inhibitors of reverse serotonin capture in pts with RA improves clinical course of the disease, its prognosis and pts quality of life.

  11. Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps.

    Science.gov (United States)

    Kotha, Sambasivarao; Ravikumar, Ongolu; Majhi, Jadab

    2015-01-01

    A tricyclic lactam is reported in a four step synthesis sequence via Beckmann rearrangement and ring-rearrangement metathesis as key steps. Here, we used a simple starting material such as dicyclopentadiene.

  12. The mechanism of action of antidepressants revised.

    Science.gov (United States)

    Ackenheil, M

    1990-01-01

    The discovery of the clinical efficacy of imipramine and of the MAO-inhibitor iproniazid intensively stimulated biochemical-pharmacological research on the mechanism of action of antidepressants. Due to these investigations, until recently an enhanced activity of the central noradrenergic and/or serotonergic transmitter system was considered essential for the clinical antidepressive action. Such enhancement could be achieved either presynaptically by blocking alpha 2-adrenergic receptors, or in the synaptic cleft by inhibiting the transmitter reuptake or the main metabolic enzyme, MAO. The common final result, especially of chronic treatment, was the down-regulation of postsynaptic beta-receptors, modulated by interaction with the serotonergic system, neuropeptides, and hormones. The delay of clinical response corresponded better with such receptor alterations. However, the introduction of new, more selective antidepressants led to new reflections upon the mechanism of action. On the level of transmitters, alpha 1-upregulation, increased activity of the dopaminergic system, an alteration in the balance between the different transmitter systems, are reported and seem to be important. Most promising are recent investigations of the second messenger systems, the adenylate cyclase system and the phosphatidylinositol system. Both systems are modulated by antidepressant drugs including lithium and carbamazepine. These second messengers, in turn, modulate the phosphorylation status of neuronal proteins via protein kinase, which may lead to elevations of the above mentioned receptors and again their transduction systems.

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

    Science.gov (United States)

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

    2017-01-01

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

  14. Approches de synthèse du tricycle ABC du FR182877.

    OpenAIRE

    Funel, Jacques-Alexis

    2004-01-01

    This manuscript describes the work performed at the Ecole Polytechnique (November 2001 - September 2004) under the direction of Dr. Joëlle Prunet Synthesis in the Laboratory Organic headed by Professor Samir Zard. It details several approaches to synthesis of the tricycle ABC of FR182877, a new antimitotic agent found naturally in 1998. After presenting the FR182877 and different approaches to literature its total synthesis, the retrosynthesis proposed to construct the tricyclic ABC system us...

  15. Special focus on antidepressants

    OpenAIRE

    Balk-Møller, Carl August; Mogensen, Sofia Lin; Raatræ Lundstein, Sarah; Haubroe Larsen, André; Lohse, Mayasarah; Reininger Ardilsø, Lisa; Henrysdóttir, Gu∂run; Sondergaard, Nikolai

    2014-01-01

    This study examines the developments of SSRIs and the presence of them in the market. Dr. Peter Gøtszche’s book “Deadly Medicines and Organized Crime”, claims that scientific fraud is a big part of the pharmaceutical industry and the whole healthcare system in general. Through analyzing Peter Gøtszche’s book and several of his sources, the study aims to create a roadmap in the project, that resembles the process of the antidepressant drugs have to go through, to go from an idea to a patient. ...

  16. Antidepressants for Children and Teens

    Science.gov (United States)

    ... of antidepressants to treat pediatric-onset depression and anxiety disorders: A developmental perspective. Psychotherapy and Psychosomatics. 2013;82:129. Gordon MS, et al. Do antidepressants make children and adolescents suicidal? Journal of Paediatrics and Child Health. 214;50:847. ...

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

    Science.gov (United States)

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

    2015-05-19

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

  18. Risk of vaginal bleeding and postpartum hemorrhage after use of antidepressants in pregnancy: a study from the Norwegian Mother and Child Cohort Study.

    Science.gov (United States)

    Lupattelli, Angela; Spigset, Olav; Koren, Gideon; Nordeng, Hedvig

    2014-02-01

    This study aimed to examine obstetric bleeding outcomes after exposure during pregnancy to selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic (TCAs), and other antidepressants (OADs).The Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway constituted the data source for the present study. We included 57,279 pregnant women, of which 1.02% reported use of antidepressants during pregnancy, mostly SSRIs/SNRIs (0.92%). We categorized exposure according to antidepressant use in pregnancy (SSRIs/SNRIs, n = 527; TCAs/OADs, n = 59; nonexposed, nondepressed, n = 55,411) with inclusion of a disease comparison group (nonexposed, depressed, n = 1282). We used logistic regression to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI) for vaginal bleeding outcomes in pregnancy and postpartum hemorrhage.Compared with nonexposed subjects, first trimester exposure to SSRIs/SNRIs or TCAs/OADs did not confer any increased risk of vaginal bleeding in early pregnancy (aOR, 0.91; 95% CI, 0.72-1.16 and aOR, 0.83; 95% CI, 0.36-1.92, respectively). No increased risk for vaginal bleeding in midpregnancy was observed among users of SSRIs/SNRIs (aOR, 0.81; 95% CI, 0.50-1.31) or TCAs/OADs (aOR, 0.96; 95% CI, 0.26-3.53) in second trimester. Exposure to SSRIs/SNRIs during gestational week 30 to childbirth did not confer any increased risk of postpartum hemorrhage after vaginal (aOR, 0.90; 95% CI, 0.47-1.74) or cesarean (aOR, 1.47; 95% CI, 0.51-4.22) delivery. Women in the disease comparison group presented a significant moderate increased risk of vaginal bleeding in early pregnancy (aOR, 1.22; 95% CI, 1.06-1.39) and midpregnancy (aOR, 1.28; 95% CI, 1.07-1.55) but not postpartum.Among this Norwegian cohort of pregnant women, use of antidepressants in pregnancy was not associated with any obstetrical bleeding outcome.

  19. Simple, Rapid and Sensitive UV-Visible Spectrophotometric Method for Determination of Antidepressant Amitriptyline in Pharmaceutical Dosage Forms

    OpenAIRE

    Pankaj Soni; Deepak Sinha; Rajmani Patel

    2013-01-01

    The paper describes a new and simple approach for spectrophotometric determination of tricyclic antidepressant drug amitriptyline. Enhancement of the colour intensity of the Fe(III)-SCN− complex on addition of the drug amitriptyline forms the basis of the proposed method. The value of molar absorptivity of the Fe(III)-SCN− amitriptyline ion pair complex in terms of the drug lies in the range of (2.82–3.36) × 103 L·mol−1·cm−1 at the absorption maximum 460 nm. The detection limit of the method ...

  20. Antidepressant-like drug effects in juvenile and adolescent mice in the tail suspension test: Relationship with hippocampal serotonin and norepinephrine transporter expression and function.

    Directory of Open Access Journals (Sweden)

    Nathan C Mitchell

    2013-10-01

    Full Text Available Depression is a major health problem for which most patients are not effectively treated. This problem is further compounded in children and adolescents where only two antidepressants [both selective serotonin reuptake inhibitors (SSRIs] are currently approved for clinical use. Mouse models provide tools to identify mechanisms that might account for poor treatment response to antidepressants. However, there are few studies in adolescent mice and none in juvenile mice. The tail suspension test (TST is commonly used to assay for antidepressant-like effects of drugs in adult mice. Here we show that the TST can also be used to assay antidepressant-like effects of drugs in C57Bl/6 mice aged 21 (juvenile and 28 (adolescent days post-partum (P. We found that the magnitude of antidepressant-like response to the SSRI escitalopram was less in P21 mice than in P28 or adult mice. The smaller antidepressant response of juveniles was not related to either maximal binding (Bmax or affinity (Kd for [3H]citalopram binding to the serotonin transporter (SERT in hippocampus, which did not vary significantly among ages. Magnitude of antidepressant-like response to the tricyclic desipramine was similar among ages, as were Bmax and Kd values for [3H]nisoxetine binding to the norepinephrine transporter (NET in hippocampus. Together, these findings suggest that juvenile mice are less responsive to the antidepressant-like effects of escitalopram than adults, but that this effect is not due to delayed maturation of SERT in hippocampus. Showing that the TST is a relevant behavioral assay of antidepressant-like activity in juvenile and adolescent mice sets the stage for future studies of the mechanisms underlying the antidepressant response in these young populations.

  1. Successful antidepressant treatment for five terminally ill cancer patients with major depression, suicidal ideation and a desire for death.

    Science.gov (United States)

    Kugaya, A; Akechi, T; Nakano, T; Okamura, H; Shima, Y; Uchitomi, Y

    1999-11-01

    In the debate on euthanasia and physician-assisted suicide, we have to exclude terminally ill patients in whom the desire for death is caused by major depression. However, it is still not clear to what degree major depression can be treated by psychiatric intervention in this setting. We evaluated the effect of antidepressant treatment in terminally ill cancer patients. Six cancer patients with suicidal ideas thought to be due to major depression were treated with tricyclic antidepressants. Three had requested terminal sedation to relieve them from their suffering. The median survival of five of these patients was 4 weeks after diagnosis; one was lost to follow-up. The efficacy of the antidepressant treatment was assessed using the Hamilton Rating Scale for Depression (HRSD). One week after the start of treatment with antidepressants, five of the six patients showed a marked improvement in their mood and showed no further suicidal thoughts or requests for terminal sedation. The average reduction in the HRSD score was 23.4 points (14-38; SD = 9. 9). Antidepressant treatment can be effective in alleviating the desire for death due to major depression, even in terminally ill cancer patients.

  2. Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid.

    Science.gov (United States)

    Peña, E; Mata, M; López-Manzanares, L; Kurtis, M; Eimil, M; Martínez-Castrillo, J C; Navas, I; Posada, I J; Prieto, C; Ruíz-Huete, C; Vela, L; Venegas, B

    2016-03-19

    Although antidepressants are widely used in Parkinson's disease (PD), few well-designed studies to support their efficacy have been conducted. These clinical guidelines are based on a review of the literature and the results of an AMN movement disorder study group survey. Evidence suggests that nortriptyline, venlafaxine, paroxetine, and citalopram may be useful in treating depression in PD, although studies on paroxetine and citalopram yield conflicting results. In clinical practice, however, selective serotonin reuptake inhibitors are usually considered the treatment of choice. Duloxetine may be an alternative to venlafaxine, although the evidence for this is less, and venlafaxine plus mirtazapine may be useful in drug-resistant cases. Furthermore, citalopram may be indicated for the treatment of anxiety, atomoxetine for hypersomnia, trazodone and mirtazapine for insomnia and psychosis, and bupropion for apathy. In general, antidepressants are well tolerated in PD. However, clinicians should consider the anticholinergic effect of tricyclic antidepressants, the impact of serotonin-norepinephrine reuptake inhibitors on blood pressure, the extrapyramidal effects of antidepressants, and any potential interactions between monoamine oxidase B inhibitors and other antidepressants. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  3. An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts.

    Science.gov (United States)

    Berndt, Ernst R; Bhattacharjya, Ashoke; Mishol, David N; Arcelus, Almudena; Lasky, Thomas

    2002-03-01

    We are not aware of any published research that quantifies and compares the importance of effectiveness and side effects for pharmaceutical sales, and that simultaneously incorporates the impacts of marketing efforts on the diffusion of new pharmaceutical agents in the U.S. The overall level and market share success of the various selective serotonin reuptake inhibitors ( SSRIs ) relative to a representative older generation tricyclic (such as amitriptyline) provides a useful focus for studying such issues. To model jointly the marketing and sales relationships of the SSRIs in the U.S., to quantify the extent to which marketing efforts are responsive to the availability of new scientific information accompanying changes in quality and increases in product variety, and in turn to assess how the new FDA indication approvals and the enhanced marketing initiatives involving product quality and variety affect sales of the SSRI and other novel antidepressants. Quarterly US sales, price, quantity and marketing data 1988Q1-1997Q4 are taken from IMS Health for the eight new antidepressants introduced into the US during this time period. Measures of physician-perceived quality attributes of the antidepressants are drawn from Market Measures, Inc., a medical survey research firm. These data are used to construct measures of product quality (effectiveness and side effect profile), and attribute variety across all antidepressants. Multivariate regression methods are used in estimating parameters of a marketing efforts model, a sales demand model encompassing the aggregate of the newer antidepressants, and a product share model. Simulation methods are employed to quantify elasticities. Since 1988, and relative to amitriptyline, there has been only a rather modest increase in the perceived average effectiveness of the SSRIs and related products, but the side effect profiles have improved substantially. Variety measures for effectiveness show greater increases over time than do

  4. Tricyclic sesquiterpene copaene prevents H2O2-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hasan Turkez

    2014-02-01

    Full Text Available Aim: Copaene (COP, a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and anticarcinogenic features. But, very little information is known about the effects of COP on oxidative stress induced neurotoxicity. Method: We used hydrogen peroxide (H2O2 exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of COP in H2O2-induced toxicity in rat cerebral cortex cell cultures for the first time. For this purpose, methyl thiazolyl tetrazolium (MTT and lactate dehydrogenase (LDH release assays were carried out to evaluate cytotoxicity. Total antioxidant capacity (TAC and total oxidative stress (TOS parameters were used to evaluate oxidative changes. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG levels, the single cell gel electrophoresis (SCGE or comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Result: The results of this study showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage increased in the H2O2 alone treated cultures. But pre-treatment of COP suppressed the cytotoxicity, genotoxicity and oxidative stress which were increased by H2O2. Conclusion: It is proposed that COP as a natural product with an antioxidant capacity in mitigating oxidative injuries in the field of neurodegenerative diseases. [J Intercult Ethnopharmacol 2014; 3(1.000: 21-28

  5. Synthesis and SAR of novel tricyclic quinoxalinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)

    Energy Technology Data Exchange (ETDEWEB)

    Miyashiro, Julie; Woods, Keith W.; Park, Chang H.; Liu, Xuesong; Shi, Yan; Johnson, Eric F.; Bouska, Jennifer J.; Olson, Amanda M.; Luo, Yan; Fry, Elizabeth H.; Giranda, Vincent L.; Penning, Thomas D.; (Abbott)

    2010-09-03

    Based on screening hit 1, a series of tricyclic quinoxalinones have been designed and evaluated for inhibition of PARP-1. Substitutions at the 7- and 8-positions of the quinoxalinone ring led to a number of compounds with good enzymatic and cellular potency. The tricyclic quinoxalinone class is sensitive to modifications of both the amine substituent and the tricyclic core. The synthesis and structure-activity relationship studies are presented.

  6. Quality of the paratransit service (tricycle and its operation in Aba, Nigeria: An analysis of customers' opinions

    Directory of Open Access Journals (Sweden)

    Obioma R. Nwaogbe

    2012-11-01

    Full Text Available This study examines the quality of the paratransit service and its operations in Aba, Abia State, Nigeria, with a view to identifying its challenges and contributions to informal transport and equitable service distribution to the residents of Aba. Structured questionnaires and past literature were used as sources of data. The primary data included road networks, number of trips per day by operators, operating speed, and purpose of travel, passengers' security, tricycle speed, and waiting time. The study was conducted by using two questionnaires: one for the operators and the other for tricycle users. The total number of completed questionnaires for the survey was 100 for operators and 229 for users. The sampling technique used was random sampling from several zones of the study area. Data were analysed using percentage and Chi-square statistical techniques for testing the hypotheses with the Minitab 11.0 version package. The study found that 92% of operators reported a high level of road network deterioration, and 61% reported making 9-12 trips per day. The hypothesis test was used to study people's feelings about the attributes of the service provided for paratransit users, such as affordability, regularity, comfort and safety. It was found that there is no significant difference at the 5% level between the various categories of these respondents.

  7. Antidepressants may mitigate the effects of prenatal maternal anxiety on infant auditory sensory gating.

    Science.gov (United States)

    Hunter, Sharon K; Mendoza, Jordan H; D'Anna, Kimberly; Zerbe, Gary O; McCarthy, Lizbeth; Hoffman, Camille; Freedman, Robert; Ross, Randal G

    2012-06-01

    Prenatal maternal anxiety has detrimental effects on the offspring's neurocognitive development, including impaired attentional function. Antidepressants are commonly used during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. The authors used P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, to assess the impact of maternal anxiety and antidepressant use. A total of 242 mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean age of 76 days (SD=38). In the absence of prenatal antidepressant exposure, infants whose mothers had a history of anxiety diagnoses had diminished P50 sensory gating. Prenatal antidepressant exposure mitigated the effect of anxiety. The effect of maternal anxiety was limited to amplitude of response to the second stimulus, while antidepressant exposure had an impact on the amplitude of response to both the first and second stimulus. Maternal anxiety disorders are associated with less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant exposure. This effect may be important in considering the risks and benefits of antidepressant use during pregnancy. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects, although the cholinergic receptors involved are likely different for anxiety and antidepressant effects.

  8. 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

  9. Antidepressants and the Placebo Effect

    Science.gov (United States)

    Kirsch, Irving

    2014-01-01

    Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future. PMID:25279271

  10. Antidepressants: Can They Lose Effectiveness?

    Science.gov (United States)

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

  11. Choice of treatment with antidepressants: influencing factors.

    Science.gov (United States)

    Himmerich, Hubertus; Wranik, Dominika W

    2012-01-01

    Depressive disorders place a large burden on patients and on society. Although efficacious treatment options for unipolar depressive disorders exist, substantial gaps in care remain. In part, the challenge lies in the matching of individual patients with appropriate care. This is complicated by the steady increases in the variety of antidepressants available in the market. The goal of this study is to highlight the decision processes in the selection of antidepressants by clinicians, given that most treatments have similar clinical effectiveness profiles. We conducted a systematic literature review of studies that referred to the decisions surrounding treatment with antidepressants for the treatment of non-psychotic unipolar depression. Our analysis of the literature reveals that the choice of treatment is based on a variety of factors, of which clinical evidence is only one. These factors can be categorized into clinical factors such as illness and treatment characteristics, individual factors such as patient and physician characteristics, and contextual factors such as setting characteristics, decision supports and pharmacoeconomic aspects. Illness characteristics are defined by the type and severity of depression. Treatment characteristics include drug properties, efficacy, effectiveness and favorable as well as unintended adverse effects of the drug. Examples for patient characteristics are co-morbidities and individual preferences, and physician characteristics include knowledge, experience, values and beliefs, and the relationship with the patient. Treatment guidelines, algorithms, and most recently, computational supports and biological markers serve as decision supports.

  12. 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.

  13. Risk of nonvertebral fractures among elderly postmenopausal women using antidepressants.

    Science.gov (United States)

    Rabenda, Véronique; Bruyère, Olivier; Reginster, Jean-Yves

    2012-10-01

    To examine the association between antidepressants, including TCAs, SSRIs, and miscellaneous antidepressants and the risk of nonvertebral fractures among women with osteoporosis. This study was a post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]). A nested case-control study was performed in the placebo treated population. Adjusted logistic regression models were used to estimate the risk of nonvertebral fracture associated with the use of antidepressants. After 3 years of follow-up, 391 nonvertebral fractures cases were identified and matched to 1955 controls. Compared with non-users of antidepressants, antidepressants use was associated with an increased risk of nonvertebral fractures (adjusted OR=1.64; 95%CI, 1.03-2.62]). Particularly, there was a 2-fold risk increase (95%CI, 1.07-3.79) of nonvertebral fracture for current users of SSRIs and a 2.1-fold risk increase for subjects who were current users of TCAs (95%CI, 1.02-4.30). Among patients categorized as recent or past users, none of the classes of antidepressants were statistically associated with increased risk of nonvertebral fracture. Our findings confirm that both SSRIs and TCAs increase the risk of nonvertebral fracture in current users. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Antidepressant Treatment for Acute Bipolar Depression: An Update

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    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.

  15. 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.

  16. Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group distortions and vibrational optical activity.

    Science.gov (United States)

    Pazderková, Markéta; Profant, Václav; Hodačová, Jana; Sebestík, Jaroslav; Pazderka, Tomáš; Novotná, Pavlína; Urbanová, Marie; Safařík, Martin; Buděšínský, Miloš; Tichý, Miloš; Bednárová, Lucie; Baumruk, Vladimír; Maloň, Petr

    2013-08-22

    We investigate amide nonplanarity in vibrational optical activity (VOA) spectra of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I) and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds to amide nitrogen atoms. We have collected a full range vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H and C-D stretching vibrations. We report normal-mode analysis and a comparison of calculated to experimental VCD and ROA. The data provide band-to-band assignment and offer a possibility to evaluate roles of constrained nonplanar tertiary amide groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and ROA amide I signals, prevailing the couplets expected to arise from the amide-amide interaction. Amide-amide coupling dominates amide II (mainly C'-N stretching, modified in tertiary amides by the absence of a N-H bond) transitions (strong couplet in VCD, no significant ROA) probably due to the close proximity of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely manifestation of amide nonplanarity, showing signals of amide V (δ(oop)(N-C) at ~570 cm(-1)) and amide VI (δ(oop)(C'═O) at ~700 cm(-1) and ~650 cm(-1)) vibrations.

  17. When ageing meets the blues: Are current antidepressants effective in depressed aged patients?

    Science.gov (United States)

    Felice, Daniela; O'Leary, Olivia F; Cryan, John F; Dinan, Timothy G; Gardier, Alain M; Sánchez, Connie; David, Denis J

    2015-08-01

    "I had to wait 110 years to become famous. I wanted to enjoy it as long as possible.", Jeanne Louise Calment (1875-1997). This review summarizes current knowledge of the effects of antidepressant drugs in elderly patients (double-blind placebo (n=27) or active comparator-controlled clinical trials (n=21) indexed in Pubmed in depressed patients aged ≥60) and in aged mice (≥9 months) and middle-aged rats (≥14 months) on depression-related symptoms and cognitive performances. Finally, other potential therapeutic targets for treating depression-related disorders in elderly patients are also addressed (neurogenesis, GABAB receptor, 5-HT4 receptor, mTOR signaling). Overall, the very few published preclinical studies (n=12 in total) in middle-aged and aged rodents seem to suggest that selective serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressant drugs (TCAs) in ameliorating depression-like behavior and cognitive functions. On the other hand, results from clinical trials suggest that there is not a marked difference in efficacy and safety profiles of current marketed classes of antidepressant drugs.

  18. Treatment of childhood anxiety disorders: what is the place for antidepressants?

    Science.gov (United States)

    Muris, Peter

    2012-01-01

    Anxiety disorders represent one of the most prevalent forms of psychopathology among children and adolescents. As these problems tend to persist and have a negative impact on young people's development, there is a need for evidence-based interventions. Cognitive-behavioral therapy (CBT) is at present the treatment of first choice, but pharmacotherapy and in particular antidepressant medication may be a viable alternative or adjunct to CBT. This paper provides a detailed overview of controlled treatment outcome studies on the efficacy of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) in children and adolescents with anxiety disorders. Further, a discussion is provided on how clinically anxious youths should be preferably treated, with special focus on the position of pharmacotherapy in the treatment process. The short-term efficacy of antidepressants in anxious youths is good, and this is particularly true for SSRIs. Therefore, this type of medication should be viewed as a viable treatment option, in particular for youths with obsessive-compulsive disorder (OCD) or other severe and pervasive anxiety disorders. More research is needed on the long-term effects, the consequences of prolonged use of this type of medication for children's developing brains and the efficacy of an intervention in which CBT and SSRIs are combined.

  19. Mimosa pudica may possess antidepressant actions in the rat.

    Science.gov (United States)

    Molina, M; Contreras, C M; Tellez-Alcantara, P

    1999-11-01

    In Mexico, aqueous extracts from dried leaves of Mimosa puolica are employed to alleviate depression. In this study, the behavioral actions of aqueous extracts of M. pudica at various concentrations were tested. Rats having received saline (0.9%; 0.30 ml; I.P.), clomipramine, desipramine or several dosages of aqueous extracts from M. pudica (ml = 2.0 mg/kg; m2 = 4.0 mg/kg; m3 = 6.0 mg/kg; m4 = 8.0 mg/kg) during a 30-day period were submitted to the forced swimming test and to the test for differential reinforcement of low rates of response at 72 sec (DRL-72s). Any possible anxiolytic action resulting from several doses (ml = 2.0 mg/kg; m2 = 4.0 mg/kg; m3 = 6.0 mg/kg; m4 = 8.0 mg/kg) of extracts of M. pudica were compared with those caused by diazepam (1.3 mg/kg, I.P.) in the elevated plus-maze test. Results showed that clomipramine (1.25 mg/kg, I.P.), desipramine (2.14 mg/kg, I.P.) and M. pudica (6.0 mg/kg and 8.0 mg/kg, I.P.) reduced immobility in the forced swimming test and increased the rate of reinforcers received in the DRL-72s test; these data suggest that M. pudica produces antidepressant effects in the rat. Diazepam increased the open-arms exploration time in the elevated plus-maze test, but M. pudica did not show any comparable action at any tested dose. M. pudica therefore produced an antide-pressant-like profile similar to two tricyclic antidepressants.

  20. Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort.

    Science.gov (United States)

    Arbus, Christophe; Gardette, Virginie; Bui, Eric; Cantet, Christelle; Andrieu, Sandrine; Nourhashémi, Fati; Schmitt, Laurent; Vellas, Bruno

    2010-02-01

    Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription. REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI). A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression. The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

  1. Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice.

    Science.gov (United States)

    Iwai, Takashi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Saitoh, Akiyoshi; Sugiyama, Azusa; Oka, Jun-Ichiro

    2013-04-15

    We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) against refractory depression in adrenocorticotropic hormone (ACTH)-treated mice as a model of tricyclic antidepressant (TCA)-resistant depression. Chronic ACTH treatment (0.45 mg/kg, s.c., 14 days) weakened the antidepressant-like effects of imipramine (20 mg/kg, i.p., 6 days) in the forced-swim test (FST). Conversely, GLP-2 (3 μg/mice, i.c.v., 6 days) induced antidepressant-like effects in the ACTH-treated mice in the FST. ACTH-treatment increased basal serum corticosterone levels, with an additional increase induced by the FST. Imipramine or GLP-2 had no effect on the basal corticosterone level, but GLP-2 attenuated the additional increase caused by the FST. Moreover, GLP-2 increased 5-HT levels, but not 5-HIAA. These results suggest that GLP-2 induced antidepressant-like effects under imipramine-resistant conditions through increase in 5-HT levels.

  2. Neuroimmune endocrine effects of antidepressants

    Directory of Open Access Journals (Sweden)

    Antonioli M

    2012-02-01

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

  3. Evaluation of the Antioxidative Properties of N-Acylamino-Substituted Tricyclic Imides

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    Melek Gul

    2013-01-01

    Full Text Available New N-acylamino-substituted tricyclic imides have been screened for scavenging ability against the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•, chelating activity on ferrous ions, and reductive potential. The results were compared with synthetic antioxidants BHT, BHA, and Trolox. The compounds exhibited different levels of antioxidant activity in all tests.

  4. A Chiron-based Approach for the Synthesis of Tricyclic Tyrosine Analogue

    Institute of Scientific and Technical Information of China (English)

    LIU Fa刘发; JIAO Jiao焦姣; ZHA Hui-Yan查慧艳; YAO Zhu-Jun姚祝军

    2004-01-01

    A chiron approach-based enantioselective synthesis of designed tricyclic tyrosine analogue D-2 was developed.A SmI2-mediated free radical cyclization, an intramolecular Friedel-Crafts reaction and an intramolecular Mannich reaction served as key steps. These key steps were optimized and repeated in good yields. All the stereochemistries in the synthesis were established and confirmed.

  5. Rapid construction of the tricyclic cores of the abietane- and icetexane-type diterpenoids

    Institute of Scientific and Technical Information of China (English)

    De Lin Chen; Xiao Yu Liu; Hang Cheng; Feng Peng Wang

    2011-01-01

    A short synthesis of the tricyclic 6-6-6 and 6-7-6 ring systems of the abietane- and icetexane-type diterpenoids from a common intermediate is presented, using alleyiation and acid-catalyzed cyclization as key steps.

  6. Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity.

    Science.gov (United States)

    de Lera Ruiz, Manuel; Zheng, Junying; Berlin, Michael Y; McCormick, Kevin D; Aslanian, Robert G; West, Robert; Hwa, Joyce; Lachowicz, Jean; van Heek, Margaret

    2013-11-01

    A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test.

  7. Treating Depression: Should You Consider an Antidepressant?

    Science.gov (United States)

    ... stressful event in your life. That could be divorce, illness, job loss, or death of a friend ... you. • Thinking about suicide Antidepressants can have side effects. Most people who take antidepressants have side effects. ...

  8. Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

    Science.gov (United States)

    Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

    2016-03-01

    Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Cytisine-based nicotinic partial agonists as novel antidepressant compounds.

    Science.gov (United States)

    Mineur, Yann S; Eibl, Christoph; Young, Grace; Kochevar, Christopher; Papke, Roger L; Gündisch, Daniela; Picciotto, Marina R

    2009-04-01

    Nicotine and other nicotinic agents are thought to regulate mood in human subjects and have antidepressant-like properties in animal models. Recent studies have demonstrated that blockade of nicotinic acetylcholine receptors (nAChRs) including those containing the beta2 subunit (beta2(*)), results in antidepressant-like effects. Previous studies have shown that cytisine, a partial agonist at alpha4/beta2(*) nAChRs, and a full agonist at alpha3/beta4(*) and alpha7 nAChRs, has antidepressant-like properties in several rodent models of antidepressant efficacy; however, it is not clear whether more selective partial agonists will also be effective in these models. We tested cytisine and two derivatives, 5-bromo-cytisine (5-Br-Cyt) and 3-(pyridin-3'-yl)-cytisine (3-pyr-Cyt) for their ability to act as a partial agonist of different nAChR subtypes and to show antidepressant-like activity in C57/BL6 mice in the tail suspension, the forced-swim, and the novelty-suppressed feeding tests. 3-pyr-Cyt was a partial agonist with very low efficacy at alpha4/beta2(*) nAChRS but had no agonist effects at other nAChRs normally targeted by cytisine, and it was effective in mouse models of antidepressant efficacy. Animals showed dose-dependent antidepressant-like effects in all three behavioral paradigms. 5-Br-Cyt was not effective in behavioral tests when administered peripherally, probably because of its inability to penetrate the blood-brain barrier, because it efficiently reduced immobility in the tail suspension test when administered intraventricularly. These results suggest that novel nicotinic partial agonists may provide new possibilities for development of drugs to treat mood disorders.

  10. Novel neurological and immunological targets for salicylate-based phytopharmaceuticals and for the anti-depressant imipramine.

    Science.gov (United States)

    Ulrich-Merzenich, G; Kelber, O; Koptina, A; Freischmidt, A; Heilmann, J; Müller, J; Zeitler, H; Seidel, M F; Ludwig, M; Heinrich, E U; Winterhoff, H

    2012-07-15

    Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses. In order to allocate potential effects to the different constituents of WB, fractions of the extract with different compositions of salicyl alcohol derivative and polyphenols were also investigated. Male Sprague Dawley rats (n=12/group) were treated for 14 days (p.o.) with the WB preparation STW 33-I (group A) and its fractions (FR) (groups FR-B to E) in concentrations of 30 mg/kg. The FRs were characterized by a high content of flavone and chalcone glycosides (FR-B), flavonoid glycosides and salicyl alcohol derivatives (FR-C), salicin and related salicyl alcohol derivatives (FR-D) and proanthocyanidines (FR-E). The tricyclic antidepressant imipramine (20 mg/kg) (F) was used as positive control. The FST was performed on day 15. The cumulative immobility time was significantly (pimipramine (16%) compared to untreated controls. RNA was isolated from peripheral blood. RNA samples (group A, group FR-D, and imipramine) were further analysed by rat whole genome microarray (Agilent) in comparison to untreated controls. Quantitative PCR for selected genes was performed. Genes (>2 fold, pimipramine, included both inflammatory (e.g. IL-3, IL-10) and neurologically relevant targets. Common genes regulated by WB, FR-D and imipramine were GRIA 2 ↓, SRP54 ↓, CYP26B ↓, DNM1L ↑ and KITLG ↓. In addition, the hippocampus of rats treated (27 d) with WB (15-60 mg/kg WB) or imipramine (15 mg/kg bw) showed a slower serotonin turnover (5-hydroxyindol acetic acid/serotonin (pimipramine, by being

  11. 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.

  12. Antidepressant-resistant depression and antidepressant-associated suicidal behaviour: the role of underlying bipolarity.

    Science.gov (United States)

    Rihmer, Zoltan; Gonda, Xenia

    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 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 (hypo)manic switches and "suicide-inducing" potential of antidepressants seem to be related to the underlying bipolarity.

  13. Recent developments in the design of anti-depressive therapies: targeting the serotonin transporter.

    Science.gov (United States)

    Butler, S G; Meegan, M J

    2008-01-01

    The serotonin transporter protein (SERT) has been the target for the development of several modern antidepressants with an objective of achieving selectivity over other monoamine transporters, thereby minimising side effects observed in the older generation of tricyclic antidepressants. The clinical selective serotonin reuptake inhibitors (SSRIs) have been shown to be among the most effective therapies in the treatment of depression. However they have clinical disadvantages over other classes of antidepressant drugs such as slow onset of action nausea and sleep disruption. The negative feedback loop attributed to the presynaptic 5-HT(1A) receptors has been implicated in the "time lag" observed in many patients between the administration of the SSRI and its observed therapeutic action. In recent years the focus has been on developing compounds with dual affinity for serotonergic auto-receptors along with an inhibitory activity at SERT. These structurally diverse products promise to be the next generation of anti-depressant medicines. This review presents an analysis of the recently reported structural classes with SSRI activity and rationalises the unique relationship between their molecular properties and biological activities. Specific emphasis is placed on the development of molecular structures with dual serotonergic activity. Recent advances in the design and synthesis of single molecular entities possessing 5-HT reuptake inhibition together with 5-HT(1A), 5-HT(1B), 5-HT(1D), 5-HT(2A), DAT, NET, alpha (2)-adrenoceptor and acetylcholinesterase antagonism are reviewed. The structural studies to identify proposed SERT binding sites together with the role of structure and ligand based design in the development of more effective SSRIs are summarised.

  14. Emerging antidepressants to treat major depressive disorder.

    Science.gov (United States)

    Block, Samantha G; Nemeroff, Charles B

    2014-12-01

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

  15. Evaluation of the potential of surface enhancement Raman spectroscopy for detection of tricyclic psychotropic drugs. Case studies on imipramine and its metabolite.

    Science.gov (United States)

    Jaworska, Aleksandra; Wietecha-Posłuszny, Renata; Woźniakiewicz, Michał; Kościelniak, Paweł; Malek, Kamilla

    2011-11-21

    The potential use of surface Raman enhanced spectroscopy (SERS) for confirmatory identification and the semi-quantitative analysis of selected tricyclic antidepressants (TCAs) is examined utilizing a conventional silver colloid. Raman and SERS spectra of aqueous solutions of imipramine (Imi) and its metabolite, desipramine (Des), were recorded as the function of concentration using NIR excitation. A good linear correlation is observed for the dependence of the SERS signal at 684 cm(-1) (R(2) = 0.9997) on Imi concentration over the range of 0.75-7.5 μM. The limit of detection of imipramine in the silver colloidal solution is 0.98 μM. SERS spectra of Imi and Des were also recorded for blood plasma samples without prior purification as well as after the use of standard solid phase extraction. All spectra show the characteristic spectral profile of the molecules and moreover, stronger signal enhancement is observed for Imi in the "raw" samples as opposed to Imi extracted from a biological matrix.

  16. Fuel cycle analysis based evaluation of the fuel and emissions reduction potential of adapting the hybrid technology to tricycles

    Energy Technology Data Exchange (ETDEWEB)

    Biona, J.B.M. [Don Bosco Technical College, Mandaluyong City (Philippines); De La Salle University, Center for Engineering and Sustainable Development Research, Manila (Philippines); Culaba, A.B. [De La Salle University, Center for Engineering and Sustainable Development Research, Manila (Philippines); Purvis, M.R.I. [University of Portsmouth, Department of Mechanical Design and Engineering, Portsmouth (United Kingdom)

    2008-02-15

    A preliminary analysis has been conducted to investigate the fuel use and emissions reduction potential of incorporating hybrid systems to two stroke powered tricycles in Metro Manila. Carbureted and direct injection two stroke engine hybrid systems were investigated and compared with the impact of shifting to four stroke engines. Results showed that hybridized direct injection retrofitted two stroke powered systems would be able to provide far better environmental and fuel reduction benefits than the shift to new four strokes tricycles. It is thus recommended that the development of such technology specifically for tricycles be seriously pursued. (orig.)

  17. Stereoselective synthesis of a highly oxygenated decahydrocyclopenta[g]chromene derivative: the common tricyclic framework of leucosceptrine and leucosesterterpenone.

    Science.gov (United States)

    Abe, Hideki; Horii, Yuri; Hagiwara, Megumi; Kobayashi, Toyoharu; Ito, Hisanaka

    2015-04-11

    Stereoselective construction of the highly oxygenated decahydrocyclopenta[g]chromene skeleton, which is the tricyclic core of leucosceptrine, which possesses prolylendopeptidase inhibitory activity, and leucosesterterpenone, which exhibits anti-angiogenic activity, from Leucosceptrum canum, was achieved.

  18. Synthesis, structure characterizations, and theoretical studies of novel tricyclic multiple(urea) molecules

    Science.gov (United States)

    Zhang, Junlin; Liu, Yingzhe; Bi, Fuqiang; Zhou, Jing; Wang, Bozhou

    2017-08-01

    Three novel Bn-protected tricyclic multiple(urea) molecules were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and elementary analysis. Structures of the Bn-protected tricyclic tris(urea) and bis(urea) molecules were further characterized by X-ray single-crystal diffraction analysis, indicating the urea carbonyl group has great influence on the molecular conformation and chemical reactivity. The electrostatic potentials on isosurfaces of electron density of the crystal structures obtained were studied by B3LYP/6-311G(d,p) method and Hirshfeld surface analysis were carried out to identify and quantify the interaction nature and proportion in crystals.

  19. 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 d...

  20. 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...

  1. Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties.

    Science.gov (United States)

    Wang, Xiaojing; Barbosa, James; Blomgren, Peter; Bremer, Meire C; Chen, Jacob; Crawford, James J; Deng, Wei; Dong, Liming; Eigenbrot, Charles; Gallion, Steve; Hau, Jonathon; Hu, Huiyong; Johnson, Adam R; Katewa, Arna; Kropf, Jeffrey E; Lee, Seung H; Liu, Lichuan; Lubach, Joseph W; Macaluso, Jen; Maciejewski, Pat; Mitchell, Scott A; Ortwine, Daniel F; DiPaolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Zhou, Fusheng; Currie, Kevin S; Young, Wendy B

    2017-06-08

    In our continued effort to discover and develop best-in-class Bruton's tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.

  2. The importance of new antidepressants in the treatment of anxiety/depressive disorders.

    Science.gov (United States)

    Boerner, R J; Möller, H J

    1999-07-01

    Patients suffering from anxiety and depression are often seen in clinical practice. In accordance with the diagnostic criteria of DSM-III/IV and ICD-10, respectively, there may be various combinations of symptoms and degrees of severity. The symptoms of these patients may range from subthreshold anxiety or depression to a combination of anxiety and depressive disorders. Besides giving an extensive survey of diagnostic problems and the epidemiological incidence of such combinations, pharmacotherapeutic approaches are critically reviewed. Metaanalyses have shown that various serotonin reuptake inhibitors (SSRI) are equivalent, if not superior, to tricyclic antidepressants (TCA) in their anti-anxiety effectiveness. Hence, SSRI may be considered a therapy of choice, not least on account of very few adverse effects and good tolerance. More recent antidepressants are under scrutiny for their anti-anxiety efficacy. Citalopram, venlafaxine and, because of its established sedative action, nefazodone seem to be particularly suited to fill a possible therapeutic gap and to provide agitated patients with an alternative to TCA.

  3. Outcome measures of antidepressive therapy.

    Science.gov (United States)

    Rosenberg, R

    2000-01-01

    A variety of outcome measures assessing antidepressive therapy are available. However, in randomized clinical trials, the Hamilton Rating Scale for Depression (HAM-D) is often the primary outcome measure. Results from factor analysis and Rasch item analysis indicate that the HAM-D is heterogeneous and that the sum of items scores may not be an adequate measure of the severity of depression. A Melancholia Scale of 11 items has been suggested as a more valid measure of the core symptoms of affective syndrome. Other global outcome measures, focusing on health-related quality of life issues and on social functioning as well as macro-economic analyses are also used in depression. Applying stringent and well-documented outcome measures in randomized clinical trials of antidepressants may give the clinician a better indication of the most appropriate drug for treatment of the individual patient.

  4. Do Statins Have Antidepressant Effects?

    DEFF Research Database (Denmark)

    Köhler-Forsberg, Ole; Gasse, Christiane; Berk, Michael

    2017-01-01

    and limited by low generalizability, and some early observational studies have pointed towards potential neuropsychiatric adverse effects of statin treatment. Nevertheless, based on the good tolerability and general safety of the statins, researchers are currently investigating the potential antidepressant......Statins are used widely in primary and secondary prevention of cardiovascular disease; a treatment effect that has long been thought to be due to their cholesterol-lowering properties. However, statins also have a wide range of anti-inflammatory effects independent of their lipid......-lowering mechanisms. In depression, low-grade inflammation is a replicated finding, and several studies have shown antidepressant properties of diverse anti-inflammatory drugs. Large observational studies have suggested reduced risks of depression amongst those taking statins, an effect that is thought...

  5. Role of corticosteroids in the antidepressant response

    Directory of Open Access Journals (Sweden)

    Pierscionek T

    2014-11-01

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

  6. 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

    2016-11-03

    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

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

    Science.gov (United States)

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

    2012-11-14

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

  8. Newer antidepressants and panic disorder: a meta-analysis.

    Science.gov (United States)

    Andrisano, Costanza; Chiesa, Alberto; Serretti, Alessandro

    2013-01-01

    Selective serotonin reuptake inhibitors and venlafaxine are currently considered as first-line agents for patients with panic disorder (PD). However, a systematic comparison of newer antidepressants for the treatment of PD is lacking thus far. Eligible studies focusing on PD patients treated with newer antidepressants were entered in the Cochrane Collaboration Review Manager. Our primary outcome measure was the mean change in panic symptoms from the baseline to the endpoint in patients treated with antidepressants as compared with those treated with placebo. Secondary outcome measures included the mean change in the overall anxiety scores and dropout rates. Sensitivity analyses were also carried out. Fifty studies focusing on 5236 patients were included. The following antidepressants were significantly superior to placebo for PD patients with the following increasing order of effectiveness: citalopram, sertraline, paroxetine, fluoxetine, and venlafaxine for panic symptoms and paroxetine, fluoxetine, fluvoxamine, citalopram, venlafaxine, and mirtazapine for overall anxiety symptoms. Aside from reboxetine and fluvoxamine, all drugs were associated with significantly lower dropout rates as compared with placebo. Several clinical variables moderated clinical outcomes. However, because of some inconsistencies across the studies and limited evidence for some drugs under investigation, further head-to-head comparisons are required.

  9. Antidepressant psychopharmacology and the social brain.

    Science.gov (United States)

    Novick, Andrew M

    2011-01-01

    Antidepressant drugs are a mainstay in psychiatric treatment and have the ability to influence neural substrates related to social bonding and interaction. This article explores the potential neurobiological overlap between social attachment and antidepressant mechanisms and reviews work related to the effects of antidepressants on separation distress, social affiliation, dominance hierarchies, romantic love, and socio-emotional processing. It is proposed that similarities between antidepressant pharmacology and the neurobiological effects of an effective care-giver may help create a sense of safety that in turn promotes changes in behavior and mood.

  10. 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

  11. 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.

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

    Science.gov (United States)

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

    2017-04-01

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

  13. Mitochondrial dynamics in the hippocampus is influenced by antidepressant treatment in a genetic rat model of depression

    DEFF Research Database (Denmark)

    Chen, F.; Wegener, Gregers; Madsen, T. M.;

    2013-01-01

    number in hippocampus. All rats were injected imipramine (a classic tricyclic antidepressant) or saline (i.p) once daily for 14 days on normal rats (10 mg/kg) and for 25 days on the Flinders Sensitive Lines (FSL) rats and their controls the Flinders Resistant Line (FRL) rats (15 mg/kg), a genetic rat...... of mitochondria in CA1SR displayed significantly smaller in the FSL-saline group compared to FRL-saline group and SD-saline group. But the mean volume of mitochondria showed significantly bigger in the FSL-saline group compared to FRL-saline group and SD-saline group. Following treatment, the FSL-imipramine group...... and SD-saline group. Impramine treatment can significantly increase the mitochondria numerical density and the number of mitochondria in FSL-imipramine group. Our results support the mitochondria plasticity hypothesis that depressive disorders may be related to impairments of mitochondria plasticity...

  14. Effects of depression, anxiety, comorbidity, and antidepressants on resting-state heart rate and its variability: an ELSA-Brasil cohort baseline study.

    Science.gov (United States)

    Kemp, Andrew H; Brunoni, Andre R; Santos, Itamar S; Nunes, Maria A; Dantas, Eduardo M; Carvalho de Figueiredo, Roberta; Pereira, Alexandre C; Ribeiro, Antonio L P; Mill, José G; Andreão, Rodrigo V; Thayer, Julian F; Benseñor, Isabela M; Lotufo, Paulo A

    2014-12-01

    Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen's d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen's d, 0.42-0.95) and other antidepressants (Cohen's d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

  15. Mind your state: Insights into antidepressant nonadherence

    African Journals Online (AJOL)

    disorders, e.g. panic disorder and generalised anxiety disorder. (GAD).1 As ... professionals, the pharmacological treatment of MDD follows ... behaviour, but mostly due to comorbid cardio-metabolic ... function15 and cognitive neurocircuitry, antidepressants have a ... contribute to antidepressants not being highly effective.

  16. The risks associated with prenatal antidepressant exposure

    DEFF Research Database (Denmark)

    Pedersen, Lars Henning

    2017-01-01

    Introduction The prevalence of depression in pregnancy is over 10% and a significant proportion of pregnant women use antidepressant medication. The safety of antidepressants in pregnancy is controversial, partly due to methodological challenges. The conflicting results in the literature may, how...

  17. Palladium complexes of a new type of N-heterocyclic carbene ligand derived from a tricyclic triazolooxazine framework

    Indian Academy of Sciences (India)

    Manoj Kumar Gangwar; Alok Ch Kalita; Prasenjit Ghosh

    2014-09-01

    A new type of tricyclic triazolooxazine derived N-heterocyclic carbene precursors were developed by the alkylation reaction of a tricyclic triazolooxazine framework. In particular, the reaction of 5a,6,7,8,9,9ahexahydro-4-benzo[][1,2,3]triazolo[1,5-][1,4]oxazine with methyl iodide and ethyl iodide yielded the tricyclic triazolooxazine derived N-heterocyclic carbene precursors, (1−2)a, in 67−84% yield. The tricyclic triazolooxazinium iodide salts, (1−2)a, underwent metallation in a straight forward manner upon treatment with PdCl2 in the presence of K2CO3 in pyridine to give the trans-{3-(R)-5a,6,7,8,9,9a-hexahydro-4-benzo[][1,2,3]triazolo[1,5-][1,4]oxazin-4-ylidene} PdI2(pyridine) [R = Me (1b), Et (2b)] complexes in 23−25% yield. The new tricyclic triazolooxazine derived N-heterocyclic carbene moiety, as stabilized upon binding to palladium in the (1−2)b complexes, was structurally characterized by the X-ray single crystal diffraction studies.

  18. Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

    Science.gov (United States)

    Bahrin, Lucian G; Hopf, Henning; Jones, Peter G; Sarbu, Laura G; Babii, Cornelia; Mihai, Alina C

    2016-01-01

    Summary A structure–activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms. PMID:27340492

  19. Ligubenzocycloheptanone A, a Novel Tricyclic Butenolide with a 6/7/5 Skeleton from Ligusticum chuanxiong

    Science.gov (United States)

    Han, Bing; Zhang, Xu; Feng, Zi-Ming; Jiang, Jian-Shuang; Li, Li; Yang, Ya-Nan; Zhang, Pei-Cheng

    2016-07-01

    Ligubenzocycloheptanone A (1), a novel tricyclic butenolide with a 6/7/5-membered ring skeleton, was isolated from the rhizome of Ligusticum chuanxiong. Its unusual structure was determined using UV, IR, HRESIMS, 1D and 2D NMR data, X-ray diffraction crystallography and by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. 1 possessed a benzocycloheptanone core featuring butyrolactone, which is rarely observed in nature. A possible biosynthetic pathway was proposed. Ligubenzocycloheptanone A showed strong radical scavenging activity with an IC50 value of 2.3 μM.

  20. 1,4-Benzodiazepine N-Nitrosoamidines: Useful Intermediates in the Synthesis of Tricyclic Benzodiazepines

    Directory of Open Access Journals (Sweden)

    Carlos del Pozo

    2006-08-01

    Full Text Available 1,4-Benzodiazepine N-nitrosoamidines have been used as scaffolds for the preparation of different tricyclic derivatives. Replacement of the N-nitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1-amino-2-propanol, followed by an acid-catalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively, in good yields. When acetylhydrazine is used as a nucleophile, the overall process provides an alternative route to alprazolam (1b and triazolam (1c, respectively.

  1. Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

    Directory of Open Access Journals (Sweden)

    Lucian G. Bahrin

    2016-05-01

    Full Text Available A structure–activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms.

  2. Cross-resistance with dieldrin of a novel tricyclic dinitrile GABA receptor antagonist

    Science.gov (United States)

    Matsuda, Kazuhiko; Hosie, Alastair M; Holyoke, Caleb W; Rauh, James J; Sattelle, David B

    1999-01-01

    A novel tricyclic dinitrile, KN244, blocked the wild-type (dieldrin-sensitive) homo-oligomeric γ-aminobutyric acid (GABA)-gated chloride channel of Drosophila melanogaster expressed in Xenopus oocytes. Sensitivity to the block by KN244 of the response to 30 μM GABA (IC50=41.6 nM, wild-type RDLac) was reduced abut 100 fold (IC50=4.5 μM) in the dieldrin-resistant (RDLacA302S) form of RDL. PMID:10455279

  3. Discontinuation syndrome in newborns whose mothers took antidepressants while pregnant or breastfeeding.

    Science.gov (United States)

    Hale, Thomas W; Kendall-Tackett, Kathleen; Cong, Zhen; Votta, Richard; McCurdy, Fred

    2010-12-01

    This study compared mothers' report of symptoms of discontinuation syndrome in infants exposed to antidepressants both in utero and during lactation to infants who were exposed only during lactation. This is a convenience sample of 930 women breastfeeding women who answered an online questionnaire about antidepressant use while pregnant and breastfeeding. All 930 women had taken antidepressants while breastfeeding, and 527 had also taken antidepressants during pregnancy. There were no participants in the present study who had taken antidepressants only during pregnancy. The questionnaire was posted on the first author's Medications and Breastfeeding Forum. There was no advertising of this study, nor were efforts made to recruit women into this study beyond posting a notice on the website. The questionnaire included a list of symptoms that mothers may have observed in their infants during the newborn period, as well as demographic questions, and questions about antidepressant use during pregnancy and lactation. The majority of women reported that their infants never experienced the symptoms of discontinuation syndrome. Twenty-five percent reported infant irritability. A smaller percentage reported inconsolable crying (17%), low body temperature (14%), and significant problems with eating and sleeping (15%). Logistic regression revealed that mothers who took antidepressants while pregnant and then during breastfeeding were two to eight times more likely to report symptoms of discontinuation syndrome than women who took them only while breastfeeding. Discontinuation symptoms were more likely to occur in infants whose mothers took medications with shorter half-lives. Discontinuation syndrome does occur in a small percentage of infants exposed to antidepressants in utero. Mothers reported a higher frequency of discontinuation syndrome after in utero exposure followed by breastfeeding than when infants were exposed to antidepressants only during lactation.

  4. Assessing disruptions in adherence to antidepressant treatments after breast cancer diagnosis.

    Science.gov (United States)

    Chou, Yi-Ting; Winn, Aaron N; Rosenstein, Donald L; Dusetzina, Stacie B

    2017-06-01

    Long-term treatment with antidepressants can lessen the symptoms of depression, but health-related crises-such as a cancer diagnosis-may disrupt ongoing depression care. The study aims to estimate the effect of receiving a breast cancer diagnosis on antidepressant adherence among women with depression. Using SEER-Medicare administrative claims, we identified women aged 65+ with newly diagnosed breast cancer between 2008 and 2011, who were diagnosed with depression and used antidepressants during the year before pre-diagnosis year. We compared antidepressant adherence among women with breast cancer to similar women without cancer using generalized estimation equations. Antidepressant adherence was estimated using the proportion of days covered 1 year before and after the index date. We included 1142 women with breast cancer and pre-existing depression and 1142 matched non-cancer patients with pre-existing depression. Mean antidepressant adherence was similar for both groups in the year before and after the index date (all around 0.71); adherence decreased by approximately 0.01 following breast cancer diagnosis in cancer group, with similar reductions among non-cancer group (p = 0.19). However, substantial proportion of patients had inadequate adherence to antidepressants in the post-diagnosis period, and almost 40% of patients in each group discontinued antidepressants over the study period. Antidepressant adherence was not associated with receiving a breast cancer diagnosis beyond what would have been expected in a similar cohort of women without cancer; however, adherence was poor among both groups. Ensuring adequate ongoing depression care is important to improve cancer care and patient quality of life in the long term. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test.

    Science.gov (United States)

    Cryan, John F; Page, Michelle E; Lucki, Irwin

    2002-02-01

    The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5-20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral noradrenergic bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral noradrenergic bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the dorsal noradrenergic bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective noradrenergic neurotoxin N-(2-chloroethyl)-N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the dorsal noradrenergic bundle nor the ventral noradrenergic bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct noradrenergic pathways exert opposing influences

  7. alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.

    Science.gov (United States)

    Doze, Van A; Handel, Evelyn M; Jensen, Kelly A; Darsie, Belle; Luger, Elizabeth J; Haselton, James R; Talbot, Jeffery N; Rorabaugh, Boyd R

    2009-08-18

    Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive-compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of alpha(1)-adrenergic receptors (alpha(1)-ARs). Yet, it is unclear whether increased alpha(1)-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant alpha(1A)-ARs (CAM alpha(1A)-AR) or CAM alpha(1B)-ARs were used to examine the effects of alpha(1A)- and alpha(1B)-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM alpha(1A)-AR mice, but not CAM alpha(1B)-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective alpha(1)-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an alpha(1A)-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM alpha(1A)-AR mice but not in CAM alpha(1B)-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM alpha(1A)-AR, and CAM alpha(1B)-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that alpha(1A)- and alpha(1B)-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that alpha(1A)-ARs may be a useful therapeutic target for the treatment of depression.

  8. α1A- and α1B-Adrenergic Receptors Differentially Modulate Antidepressant-Like Behavior in the Mouse

    Science.gov (United States)

    Doze, Van A.; Handel, Evelyn M.; Jensen, Kelly A.; Darsie, Belle; Luger, Elizabeth J.; Haselton, James R.; Talbot, Jeffery N.; Rorabaugh, Boyd R.

    2009-01-01

    Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of α1-adrenergic receptors (α1-ARs). Yet, it is unclear whether increased α1-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant α1A-ARs (CAM α1A-AR) or CAM α1B-ARs were used to examine the effects of α1A- and α1B-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM α1A-AR mice, but not CAM α1B-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective α1-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an α1A-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM α1A-AR mice but not in CAM α1B-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM α1A-AR, and CAM α1B-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that α1A- and α1B-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that α1A-ARs may be a useful therapeutic target for the treatment of depression. PMID:19540213

  9. Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons

    Directory of Open Access Journals (Sweden)

    McMurray Cynthia T

    2009-07-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion mutation in the coding region of a novel gene. The mechanism of HD is unknown. Most data suggest that polyglutamine-mediated aggregation associated with expression of mutant huntingtin protein (mhtt contributes to the pathology. However, recent studies have identified early cellular dysfunctions that preclude aggregate formation. Suppression of aggregation is accepted as one of the markers of successful therapeutic approaches. Previously, we demonstrated that tricyclic pyrone (TP compounds efficiently inhibited formation of amyloid-β (Aβ aggregates in cell and mouse models representing Alzheimer's Disease (AD. In the present study, we aimed to determine whether TP compounds could prevent aggregation and restore early cellular defects in primary embryonic striatal neurons from animal model representing HD. Results TP compounds effectively inhibit aggregation caused by mhtt in neurons and glial cells. Treatment with TP compounds also alleviated cholesterol accumulation and restored clathrin-independent endocytosis in HD neurons. Conclusion We have found that TP compounds not only blocked mhtt-induced aggregation, but also alleviated early cellular dysfunctions that preclude aggregate formation. Our data suggest TP molecules may be used as lead compounds for prevention or treatment of multiple neurodegenerative diseases including HD and AD.

  10. Antidepressants alleviate the impact of reinforcer downshift.

    Science.gov (United States)

    Nikiforuk, Agnieszka; Popik, Piotr

    2009-01-01

    Depressive disorder is associated with problems of coping with life's difficulties, including episodes of frustration and disappointment, operationally defined as an unexpected reinforcer omission or a reduction of reinforcer magnitude. In a novel model aimed at detecting potential antidepressants, rats were trained in the operant task under progressive ratio schedule of reinforcement with the break point (BP, the value of the last completed response ratio) as a behavioral endpoint. In the main experiment, a 32% sucrose solution was initially used as the reinforcer. Once the stable responding was achieved, for the following 5 days animals were treated once daily with the experimental drugs, and were offered a 4% sucrose solution instead. In vehicle-treated controls, the reduction of sucrose concentration resulted in a decrease in responding from a BP of about 40 (totaling 166 responses) to a BP of about 9 (totaling 22 responses). Chlordiazepoxide (4 and 8 mg/kg), fluoxetine (3 mg/kg), citalopram (6 mg/kg) and cocaine (2.5 and 5 mg/kg) markedly inhibited this response decrement, while fluoxetine (6 mg/kg) augmented it. Neither desipramine (1-6 mg/kg) nor morphine (1-5 mg/kg) affected responding under the reduced sucrose concentration condition. In the control experiment, the rats have never been offered 32% sucrose solution but their responding was always maintained by 4% sucrose. Under these unchanged conditions, only cocaine (5 mg/kg) affected (increased) responding. The present results suggest that the antidepressants selectively inhibiting serotonin reuptake and a benzodiazepine anxiolytic but not psychostimulant cocaine may specifically protect animals from the effects of a reinforcer downshift.

  11. Comparative study of neuroprotective effect of tricyclics vs. trazodone on animal model of depressive disorder.

    Science.gov (United States)

    Marinescu, Ileana P; Predescu, Anca; Udriştoiu, T; Marinescu, D

    2012-01-01

    The neurobiological model of depressive disorder may be correlated with the animal model on rat, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the increase of cortisol level being specific to the model of depression in women. The neurobiological model of depression in women presents vulnerabilities for some cerebral structures (hippocampus, frontal cortex, cerebral amygdala). A decrease of frontal cortex and hippocampus volumes are recognized in depressive disorder in women, depending on duration of disease and antidepressant therapy. Neurobiological vulnerability may be pronounced through cholinergic blockade. The purpose of the study was to highlight the cytoarchitectural changes in the frontal cortex and hippocampus by comparing two antidepressant substances: amitriptyline with a strong anticholinergic effect and trazodone, without anticholinergic effect. The superior neuroprotective qualities of trazodone for the frontal cortex, hippocampus and dentate gyrus are revealed. The particular neurobiological vulnerability of depression in women requires a differentiated therapeutic approach, avoiding the use of antidepressants with anticholinergic action.

  12. Rapid antidepressant effects of Yueju: A new look at the function and mechanism of an old herbal medicine.

    Science.gov (United States)

    Ren, Li; Chen, Gang

    2017-05-05

    Yueju is a traditional herbal medicine which consists of five herbs and formulated to treat depression-related syndromes 800 years ago. Yueju is still widely prescribed to treat conditions which include digestive dysfunction and depression. Recently, Yueju has been shown to promote a fast-onset antidepressant effect clinically and in preclinical studies. Because conventional antidepressants have a delayed onset in treating depression, the novelty of Yueju's rapid antidepressant effect and its underlying mechanism are of great significance both clinically and scientifically. To review the use of Yueju for treatment of mood-related syndromes, and particularly its use in depression. To evaluate recent evidence of Yueju rapid antidepressant actions, based on new findings at behavioral and molecular levels. To suggest direction for future studies to address further scientific issues. Reports regarding to the history and current use of Yueju are summarized. Recent progress on rapid antidepressant effects of Yueju, the crucial constituent, Gardenia jasminoides J.Ellis (GJ) and other herbs, are reviewed. The medical need for rapid antidepressant actions, as well as breakthrough findings using ketamine and its limitations are introduced. Studies with Yueju using a number of acute, subacute and chronic behavioral paradigms are compared with ketamine. Findings from clinical reports also support the rapid action of Yueju. Studies examine the contribution of the constituent herb GJ, in rapid antidepressant effects. Importantly, research into the mechanism of Yueju or GJ's antidepressant response indicate the importance of up-regulation in the neural circuit responsible for antidepressant activity, and highlight common and specific molecular signaling by Yueju that may explain why this herb formula has unique antidepressant activity. Preclinical and clinical studies demonstrate that Yueju confers rapid antidepressant effects. The common mechanisms shared both for ketamine and

  13. Fused tricyclic pyrrolizinones that exhibit pseudo-irreversible blockade of the NK1 receptor.

    Science.gov (United States)

    Morriello, Gregori J; Chicchi, Gary; Johnson, Tricia; Mills, Sander G; Demartino, Julie; Kurtz, Marc; Tsao, K L C; Zheng, Song; Tong, Xinchun; Carlson, Emma; Townson, Karen; Wheeldon, Alan; Boyce, Susan; Collinson, Neil; Rupniak, Nadia; Devita, Robert J

    2010-10-01

    Previously, we had disclosed a novel class of hNK(1) antagonists based on the 5,5-fused pyrrolidine core. These compounds displayed subnanomolar hNK(1) affinity along with good efficacy in a gerbil foot-tapping (GFT) model, but unfortunately they had low to moderate functional antagonist (IP-1) activity. To elaborate on the SAR of this class of hNK(1) compounds and to improve functional activity, we have designed and synthesized a new class of hNK(1) antagonist with a third fused ring. Compared to the 5,5-fused pyrrolidine class, these 5,5,5-fused tricyclic hNK(1) antagonists maintain subnanomolar hNK(1) binding affinity with highly improved functional IP-1 activity (<10% SP remaining). A fused tricyclic methyl, hydroxyl geminally substituted pyrrolizinone (compound 20) had excellent functional IP (<2% SP remaining), hNK(1) binding affinity, off-target selectivity, pharmacokinetic profile and in vivo activity. Complete inhibition of agonist activity was observed at both 0 and 24h in the gerbil foot-tapping model with an ID(50) of 0.02 mpk at both 0 and 24h, respectively.

  14. A solar electric tricycle%一种太阳能三轮电动车

    Institute of Scientific and Technical Information of China (English)

    赵林; 王志坤

    2014-01-01

    设计了一种利用清洁能源并且可以适应人们生活的太阳能三轮电动车。该三轮电动车相对于二轮电动车更稳定,都是以传统的充电方式为电动车提供动力,路途没电的状况经常发生,为人们带来很大的不便。针对这一情况设计一款智能化的三轮太阳能电动车,能使其在有光的地方通过太阳能电池板为电动车的蓄电池充电。%Design a kind of clean energy and can adapt to the people living the solar electric tricycle.The three wheeled electric vehicle with two wheel electric vehicle is more stable,are based on the traditional way of charging provides power to the electric motor car,the road no electricity situation occurs frequently,bring a lot of inconvenience for people.Solar electric tricycle a intel igent design in view of this situation,can make its are in the bright place by solar panel battery for electric vehicle charging.

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

    Science.gov (United States)

    Smardon, Regina

    2008-01-01

    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 consumption. Antidepressant consumers must negotiate the threat of stigma and the threat of commodification through the process of constructing narratives. Exploring the narrative process of identity negotiation reveals how the interconnected cultural processes of stigma and commodification are undergoing historical shifts. Among these shifts are the intensification of branding and an expansion of consumer culture. Implications for health promotion and further research are discussed.

  16. Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.

    Science.gov (United States)

    Tanaka, Satoshi; Yamada, Misa; Kitahara, Sari; Higuchi, Teruhiko; Honda, Kazuo; Kamijima, Kunitoshi; Yamada, Mitsuhiko

    2006-02-01

    Using expressed sequence tag (EST) analysis, we previously identified certain molecular machinery that mediates antidepressant effects. To date, several partial cDNA fragments, termed antidepressant-related genes (ADRGs), have been isolated as ESTs from rat brain. In the present study, we identified two of the ADRGs to be rat neuroserpin. Using real-time quantitative PCR, we demonstrated increased neuroserpin mRNA expression in rat frontal cortex after chronic treatment with several classes of antidepressants, including imipramine, fluoxetine, sertraline, and venlafaxine. Electroconvulsive treatment (ECT), another therapeutic treatment for depression, also increased neuroserpin expression in rat frontal cortex. Neuroserpin is a serine protease inhibitor that is implicated in the regulation of synaptic plasticity, neuronal migration, and axogenesis in the central nervous system. In conclusion, our results support the hypothesis that neuroserpin-mediated plastic changes in frontal cortex may underlie the therapeutic action of antidepressants and ECT.

  17. 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

  18. 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...

  19. Risk of dementia in German patients treated with antidepressants in general or psychiatric practices
.

    Science.gov (United States)

    Jacob, Louis; Bohlken, Jens; Kostev, Karel

    2017-04-01

    To study the impact of the use of antidepressants on dementia in German patients with depression treated in general (GPs) or psychiatric practices (PPs). Patients with a first-time documentation of depression with known severity level between 2010 and 2013 (index date) were identified by 1,126 general practitioners and 176 psychiatrists in the IMS Disease Analyzer database. We included patients between the ages of 60 and 80 years who had not previously received prescriptions for antidepressant drugs and had not been diagnosed with all-cause dementia prior to or on the index date. The main outcome of the study was the risk of dementia depending on antidepressant therapy. Cox proportional hazards models (dependent variable: incident dementia) were used to adjust for confounders and to estimate the effect of antidepressant therapy. A total of 22,838 patients treated in GPs and 33,112 patients treated in PPs were included in this study. Of those, 9,570, 30,321, and 16,059 individuals suffered from mild, moderate, and severe depression, respectively. Antidepressant drug use was associated with a decreased risk of dementia in patients affected by moderate (HR = 0.86, 95% CI: 0.77 - 0.95) or severe depression (HR = 0.83, 95% CI: 0.73 - 0.94). The use of antidepressants decreased dementia risk in patients with moderate or severe depression.
.

  20. Executive summary of the report by the WPA section on pharmacopsychiatry on general and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders.

    Science.gov (United States)

    Baghai, Thomas C; Blier, Pierre; Baldwin, David S; Bauer, Michael; Goodwin, Guy M; Fountoulakis, Kostas N; Kasper, Siegfried; Leonard, Brian E; Malt, Ulrik F; Stein, Dan J; Versiani, Marcio; Möller, Hans-Jürgen

    2012-02-01

    Current gold standard in the treatment of depression includes pharmacotherapeutic and psychotherapeutic strategies together with social support. Due to the actually discussed controversies concerning the differential efficacy of antidepressants, a contribution to a comprehensive clarification seems to be necessary to avert further deterioration and uncertainty from patients, relatives, and their treating psychiatrists and general practitioners. Both efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders can be confirmed. Clinically meaningful antidepressant treatment effects were confirmed in different types of studies. Methodological issues of randomized controlled studies, meta-analyses, and effectiveness studies will be discussed. Furthermore, actual data about the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties and about outcome differences in studies using antidepressants and/or psychotherapy are discussed. This is followed by a clinically oriented depiction-the differential clinical effectiveness of different pharmacodynamic modes of action of antidepressants in different subtypes of depressive disorders. It can be summarized that the spectrum of different antidepressant treatments has broadened during the last decades. The efficacy and clinical effectiveness of antidepressants is statistically significant and clinically relevant and proven repeatedly. For further optimizing antidepressant treatment plans, clearly structured treatment algorithms and the implementation of psychotherapy seem to be useful. A modern individualized antidepressant treatment in most cases is a well-tolerated and efficacious tool to minimize the negative impact of the otherwise devastating and life-threatening outcome of depressive disorders.

  1. Antidepressants: MedlinePlus Health Topic

    Science.gov (United States)

    ... antidepressants in primary care: descriptive study of... Article: Comparison chart of drugs for migraine prevention. Article: Sixty ... the sharing features on this page, please enable JavaScript. About MedlinePlus Site Map FAQs Customer Support Get ...

  2. Usefulness of antidepressants in anxiety disorders

    National Research Council Canada - National Science Library

    Ansseau, M

    2006-01-01

    ...: panic disorder, specific phobias, social phobia and generalized anxiety. After a brief description of their clinical characteristics and prevalence, it provides the general principles of treatment and mainly the specific role of antidepressant...

  3. Antidepressants versus interpersonal psychotherapy in treating ...

    African Journals Online (AJOL)

    are effective in the treatment of co-morbid depression and ..... of antidepressants in HIV-infected patients is still not guided by ..... Secretory immunoglobulin A increases during ... men with and without human immunodeficiency virus infection.

  4. Adherence to anti-depressant medication

    DEFF Research Database (Denmark)

    Buus, Niels

    2014-01-01

    The study of medicine taking is controversial as it often reveals a discrepancy between healthcare professionals' advice and patients' actual behaviour. Qualitative researchers have examined depressed people's adherence to prescriptions of antidepressants by exploring the meaning they impute to t...

  5. Antidepressants for neuroprotection in Huntington's disease: A review.

    Science.gov (United States)

    Jamwal, Sumit; Kumar, Puneet

    2015-12-15

    Huntington Disease (HD), which is characterized by abnormal dance-like movements, is a neurodegenerative disorder caused by a genetic mutation that results in an expanded polyglutamine stretch in the NH2 terminus of huntingtin protein (HTT). The principal neuropathological hallmarks of disease include loss of striatal and cortical projection neurons. HTT is ubiquitously expressed and is implicated in several cellular functions including neurogenesis, cell trafficking and brain-derived neurotrophic factor (BDNF) production. Major depression is the most common symptom among pre-symptomatic HD carriers and numerous pieces of preclinical evidence have suggested the use of antidepressants in HD not only elevates mood but also slows down the disease progression by activating different neuroprotective mechanism like BDNF/TrkB pathway, MAPK/ERK signalling, neurogenesis and Wnt signalling. HTT plays major role in neurogenesis, a physiological phenomenon that is implicated in some of the behavioral effects of antidepressants. Currently, there is no clinically available treatment that can halt or slow down the progression of HD except tetrabenazine (the only FDA approved drug); however, this drug also induces depression and sedation in patients. In this review, a brief discussion has been made about the mutant HTT that induced various cellular and molecular mechanisms underlying behavioral disorders in HD. Further, an attempt has been made to understand the various cellular mechanisms involved in mediating the neuroprotective effects of antidepressants in HD. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 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.

  7. Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine.

    Science.gov (United States)

    Fukumoto, Kenichi; Toki, Hidetoh; Iijima, Michihiko; Hashihayata, Takashi; Yamaguchi, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

    2017-04-01

    The rapid-acting and long-lasting antidepressant effects of (R,S)-ketamine have recently gained much attention. Although (S)-ketamine has been studied as an active isomer, recent evidence suggests that (R)-ketamine exhibits longer-lasting antidepressant effects than (S)-ketamine in rodents. However, the antidepressant potential of (R)-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of (R)-ketamine with those of (S)-ketamine in animal models of depression, including a model that is refractory to current medications. Both (R)-ketamine and (S)-ketamine exhibited antidepressant effects at 30 minutes as well as at 24 hours after administration in forced-swimming and tail-suspension tests in mice. At 48 hours after administration, however, (R)-ketamine still exerted a significant antidepressant effect in the tail-suspension test, whereas the effect of (S)-ketamine was no longer observed. Moreover, (R)-ketamine, but not (S)-ketamine, significantly reversed the depressive-like behavior induced by repeated treatments with corticosterone in rats at 24 hours after a single administration. This effect was attenuated by an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, suggesting the involvement of AMPA receptor stimulation in the effects. Both (R)-ketamine and (S)-ketamine exhibited practically the same exposure levels in plasma, brain, and cerebrospinal fluid in mice and rats, and both compounds were rapidly eliminated from plasma (S)-ketamine in animal models of depression. Moreover, our study is the first to demonstrate that (R)-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants.

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

    Science.gov (United States)

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  9. Prescribing patterns of medicine classified as 'antidepressants' in South African children and adolescents

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

  11. Reduced treatment-emergent sexual dysfunction as a potential target in the development of new antidepressants.

    Science.gov (United States)

    Baldwin, David S; Palazzo, M Carlotta; Masdrakis, Vasilios G

    2013-01-01

    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.

  12. 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

  13. Inhibitory effect of the antidepressant imipramine on NF-κB-dependent CXCL1 expression in TNFα-exposed astrocytes.

    Science.gov (United States)

    Lee, Young Han; Kim, Se Hyun; Kim, Yeni; Lim, Yoongho; Ha, Kyooseob; Shin, Soon Young

    2012-04-01

    Neuroinflammation is associated with the pathophysiology of various neurodegenerative diseases. Emerging evidence indicates that imipramine, a tricyclic antidepressant commonly used in depressive disorders, exhibits neuroprotective activity partly through anti-inflammatory effects. However, the molecular mechanisms underlying imipramine-mediated anti-inflammatory response are poorly understood. In this study, rat primary cultured astrocytes were used to elucidate the effect of the imipramine on TNFα-induced inflammatory responses. The results clearly demonstrated that imipramine reduced TNFα-induced CXCL1 expression through suppression of NF-κB-dependent CXCL1 promoter activity in primary astrocytes. In addition, we found that imipramine suppressed TNFα-induced phosphorylation of inhibitor of κBα (IκBα) and p65/RelA nuclear factor-κB (NF-κB), as well as the nuclear translocation of p65/RelA in primary cultured astrocytes. Chemotaxis assay demonstrated that astrocyte-derived CXCL1 contributed to migration of BV2 microglial cells toward astrocytes. This response was significantly blocked by treatment of astrocytes with imipramine or NF-κB inhibitor BAY11-7082. This study indicates that the antidepressant imipramine inhibits TNFα-induced CXCL1 expression via down-regulation of NF-κB signaling pathway in astrocytes and suggests that imipramine has a potential as an anti-inflammatory drug.

  14. Pharmacist self-reported antidepressant medication counseling.

    Science.gov (United States)

    Cannon-Breland, Michelle L; Westrick, Salisa C; Kavookjian, Jan; Berger, Bruce A; Shannon, David M; Lorenz, Raymond A

    2013-01-01

    To identify the extent of pharmacists' self-reported antidepressant counseling (SRAC) and to identify factors that may affect pharmacists' decisions to provide antidepressant counseling. Cross-sectional study. Alabama community pharmacies in 2011. Full-time pharmacists from 600 community pharmacies. Self-administered survey; three mail contacts with alternate electronic surveys were used. Pharmacists' SRAC behavior and its relationship with pharmacists' illness perceptions of depression, self-efficacy, and organizational and environmental influences. 600 surveys were sent; 22 were undeliverable, 1 was partially completed (understanding of depression, and 36% discussed options for managing adverse effects with no more than a few patients. More than one-quarter (28.6%) never asked patients whether they had barriers to taking antidepressants. Pharmacists' perceptions regarding consequences, control/cure, and the episodic nature of depression, as well as their self-efficacy, had significant relationships ( P < 0.05) with pharmacists' involvement in antidepressant counseling. Low rates of pharmacists' involvement in antidepressant counseling were reported. Pharmacists must become more involved in counseling patients about their antidepressant medications and overcoming barriers preventing greater involvement.

  15. Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

    Science.gov (United States)

    2014-11-01

    amitriptyline-induced hypotension. The objective was to determine if ILE improved hypotension (defined by a mean arterial pressure [MAP] < 60% baseline...more effective in improving hypotension (defined by a mean arterial pressure [MAP] < 60% baseline) compared to sodium bicarbon- ate for treatment of...amitriptyline overdose in a critically ill swine model. METHODS Study Design Using a porcine model of amitriptyline-induced hypo- tension , we used a

  16. Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 1 : Literature review

    NARCIS (Netherlands)

    Nijenhuis, C.M.; Ter Horst, P.G.; de Jong-van den Berg, L.T.; Wilffert, B.

    2012-01-01

    The increase in selective serotonin re-uptake inhibitor (SSRI) use during pregnancy, questions concerning abnormal development of the enteric nervous system (ENS), increase in laxative use in children and the association of fluoxetine with infantile hypertrophic pyloric stenosis (IHPS) gave rise to

  17. Mass asymmetry and tricyclic wobble motion assessment using automated launch video analysis

    Institute of Scientific and Technical Information of China (English)

    Ryan DECKER; Joseph DONINI; William GARDNER; Jobin JOHN; Walter KOENIG

    2016-01-01

    This paper describes an approach to identify epicyclic and tricyclic motion during projectile flight caused by mass asymmetries in spin-stabilized projectiles. Flight video was captured following projectile launch of several M110A2E1 155 mm artillery projectiles. These videos were then analyzed using the automated flight video analysis method to attain their initial position and orientation histories. Examination of the pitch and yaw histories clearly indicates that in addition to epicyclic motion’s nutation and precession oscillations, an even faster wobble amplitude is present during each spin revolution, even though some of the amplitudes of the oscillation are smaller than 0.02 degree. The results are compared to a sequence of shots where little appreciable mass asymmetries were present, and only nutation and precession frequencies are predominantly apparent in the motion history results. Magnitudes of the wobble motion are estimated and compared to product of inertia measurements of the asymmetric projectiles.

  18. Tricyclic Guanidine Alkaloids from the Marine Sponge Acanthella cavernosa that Stabilize the Tumor Suppressor PDCD4

    Science.gov (United States)

    Grkovic, Tanja; Blees, Johanna S.; Bayer, Magdalena M.; Colburn, Nancy H.; Thomas, Cheryl L.; Henrich, Curtis J.; Peach, Megan L.; McMahon, James B.; Schmid, Tobias; Gustafson, Kirk R.

    2014-01-01

    A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions. PMID:25196934

  19. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives.

    Science.gov (United States)

    Timoshenko, Mariya A; Kharitonov, Yurii V; Shakirov, Makhmut M; Bagryanskaya, Irina Yu; Shults, Elvira E

    2016-02-01

    A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products.

  20. Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus.

    Science.gov (United States)

    Alboni, Silvia; Benatti, Cristina; Montanari, Claudia; Tascedda, Fabio; Brunello, Nicoletta

    2013-12-05

    To gain insight into the possible immune targets of antidepressant, we evaluated the expression of several inflammatory mediators in the hypothalamus of rats chronically (28 days) treated with the serotonin selective reuptake inhibitor fluoxetine (5mg/kg, i.p.) or the tricyclic compound imipramine (15 mg/kg, i.p.). We focused our attention on the hypothalamus as it plays a key role in determining many of the somatic symptoms experienced by depressed patients. This brain region, critical also for expression of motivated behaviours, participates in the control of the hypothalamic-pituitary-adrenal axis activity and in stress response as well as coordinates physiological functions such as sleep and food intake that have been found altered in a high percentage of depressed patients. Notably, hypothalamus is a key structure for brain cytokine expression and function as it integrates signals from the neuro, immune, endocrine systems. By means of quantitative Real Time PCR experiments we demonstrated that a chronic treatment with either fluoxetine or imipramine resulted in a reduction of IL-6 and IFN-γ mRNAs and increased IL-4 mRNA expression in the rat hypothalamus. Moreover, we demonstrated that hypothalamic expression of members of IL-18 system was differentially affected by chronic antidepressant treatments. Chronically administered fluoxetine decreased IL-8 and CX3CL1 hypothalamic expression, while a chronic treatment with imipramine decreased p11 mRNA. Our data suggest that a shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus may represent a common mechanism of action of both the chronic treatments with fluoxetine and imipramine. © 2013 Published by Elsevier B.V.

  1. Antidepressant efficacy of sertraline and imipramine for the treatment of major depression in elderly outpatients

    Directory of Open Access Journals (Sweden)

    Orestes Vicente Forlenza

    2000-07-01

    Full Text Available CONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE: To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day and imipramine (150 mg/day in the first 6 weeks of the treatment of major depression in the elderly. DESIGN: A randomized double-blind parallel study with 6 weeks of follow-up. SETTING: The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo. PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION: Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS: CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS: Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01. No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7. Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS: Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.

  2. Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression

    Science.gov (United States)

    Chen, Jianjun; Deng, Xiao; Zhang, Lin; Zhao, Xiang; Qu, Zehui; Lei, Yang; Lei, Ting

    2017-01-01

    Background Brain derived neurotrophic factor (BDNF) is one of the most important regulatory proteins in the pathophysiology of major depressive disorder (MDD). Increasing numbers of studies have reported the relationship between serum/plasma BDNF and antidepressants (ADs). However, the potential effects of several classes of antidepressants on BDNF concentrations are not well known. Hence, our meta-analyses aims to review the effects of differential antidepressant drugs on peripheral BDNF levels in MDD and make some recommendations for future research. Methods Electronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, and PsycINFO were searched from 1980 to June 2016. The change in BDNF levels were compared between baseline and post-antidepressants treatment by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided. Results We identified 20 eligible trials of antidepressants treatments for BDNF in MDD. The overall effect size for all drug classes showed that BDNF levels were elevated following a course of antidepressants use. For between-study heterogeneity by stratification analyses, we detect that length of treatment and blood samples are significant effect modifiers for BDNF levels during antidepressants treatment. While both SSRIs and SNRIs could increase the BDNF levels after a period of antidepressant medication treatment, sertraline was superior to other three drugs (venlafaxine, paroxetine or escitalopram) in the early increase of BDNF concentrations with SMD 0.53(95% CI = 0.13–0.93; P = 0.009). Conclusions There is some evidence that treatment of antidepressants appears to be effective in the increase of peripheral BDNF levels. More robust evidence indicates that different types of antidepressants appear to induce differential effects on the BDNF levels. Since sertraline makes a particular effect on BDNF concentration within a short amount of time, there is

  3. Most Antidepressant Use in Primary Care Is Justified; Results of the Netherlands Study of Depression and Anxiety

    Science.gov (United States)

    Piek, Ellen; van der Meer, Klaas; Hoogendijk, Witte J. G.; Penninx, Brenda W. J. H.; Nolen, Willem A.

    2011-01-01

    Background Depression is a common illness, often treated in primary care. Many studies have reported undertreatment with antidepressants in primary care. Recently, some studies also reported overtreatment with antidepressants. The present study was designed to assess whether treatment with antidepressants in primary care is in accordance with current guidelines, with a special focus on overtreatment. Methodology We used baseline data of primary care respondents from the Netherlands Study of Depression and Anxiety (NESDA) (n = 1610). Seventy-nine patients with treatment in secondary care were excluded. We assessed justification for treatment with antidepressant according to the Dutch primary care guidelines for depression and for anxiety disorders. Use of antidepressants was based on drug-container inspection or, if unavailable, on self-report. Results were recalculated to the original population of primary care patients from which the participants in NESDA were selected (n = 10,677). Principal Findings Of 1531 included primary care patients, 199 (13%) used an antidepressant, of whom 188 (94.5%) (possibly) justified. After recalculating these numbers to the original population (n = 10,677), we found 908 (95% CI 823 to 994) antidepressant users. Forty-nine (95% CI 20 to 78) of them (5.4%) had no current justification for an antidepressant, but 27 of them (54.5%) had a justified reason for an antidepressant at some earlier point in their life. Conclusions We found that overtreatment with antidepressants in primary care is not a frequent problem. Too long continuation of treatment seems to explain the largest proportion of overtreatment as opposed to inappropriate initiation of treatment. PMID:21479264

  4. Most antidepressant use in primary care is justified; results of the Netherlands Study of Depression and Anxiety.

    Directory of Open Access Journals (Sweden)

    Ellen Piek

    Full Text Available BACKGROUND: Depression is a common illness, often treated in primary care. Many studies have reported undertreatment with antidepressants in primary care. Recently, some studies also reported overtreatment with antidepressants. The present study was designed to assess whether treatment with antidepressants in primary care is in accordance with current guidelines, with a special focus on overtreatment. METHODOLOGY: We used baseline data of primary care respondents from the Netherlands Study of Depression and Anxiety (NESDA (n = 1610. Seventy-nine patients with treatment in secondary care were excluded. We assessed justification for treatment with antidepressant according to the Dutch primary care guidelines for depression and for anxiety disorders. Use of antidepressants was based on drug-container inspection or, if unavailable, on self-report. Results were recalculated to the original population of primary care patients from which the participants in NESDA were selected (n = 10,677. PRINCIPAL FINDINGS: Of 1531 included primary care patients, 199 (13% used an antidepressant, of whom 188 (94.5% (possibly justified. After recalculating these numbers to the original population (n = 10,677, we found 908 (95% CI 823 to 994 antidepressant users. Forty-nine (95% CI 20 to 78 of them (5.4% had no current justification for an antidepressant, but 27 of them (54.5% had a justified reason for an antidepressant at some earlier point in their life. CONCLUSIONS: We found that overtreatment with antidepressants in primary care is not a frequent problem. Too long continuation of treatment seems to explain the largest proportion of overtreatment as opposed to inappropriate initiation of treatment.

  5. 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.

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

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    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.

  7. 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

  8. 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.

  9. Semen abnormalities with SSRI antidepressants.

    Science.gov (United States)

    2015-01-01

    Despite decades of widespread use, the adverse effect profile of "selective" serotonin reuptake inhibitor (SSRI) antidepressants has still not been fully elucidated. Studies in male animals have shown delayed sexual development and reduced fertility. Three prospective cohort studies conducted in over one hundred patients exposed to an SSRI for periods ranging from 5 weeks to 24 months found altered semen param-eters after as little as 3 months of exposure: reduced sperm concentration, reduced sperm motility, a higher percentage of abnormal spermatozoa, and increased levels of sperm DNA fragmentation. One clinical trial showed growth retardation in children considered depressed who were exposed to SSRls. SSRls may have endocrine disrupting properties. Dapoxetine is a short-acting serotonin reuptake inhibitor that is chemically related to fluoxetine and marketed in the European Union for men complaining of premature ejaculation. But the corresponding European summary of product characteristics does not mention any effects on fertility. In practice, based on the data available as of mid-2014, the effects of SSRI exposure on male fertility are unclear. However, it is a risk that should be taken into account and pointed out to male patients who would like to father a child or who are experiencing fertility problems.

  10. Polypharmacy with antidepressants in children and adolescents.

    Science.gov (United States)

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

    2014-07-01

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

  11. Antidepressant Specificity of Serotonin Transporter Suggested by Three LeuT-SSRI Structures

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-01

    Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

  12. Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.

    Science.gov (United States)

    Zhou, Zheng; Zhen, Juan; Karpowich, Nathan K; Law, Christopher J; Reith, Maarten E A; Wang, Da-Neng

    2009-06-01

    Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

  13. In vivo canine model comparison of cardiovascular effects of antidepressants milnacipran and imipramine.

    Science.gov (United States)

    Mitsumori, Yoshitaka; Nakamura, Yuji; Hoshiai, Kiyotaka; Nagayama, Yukitoshi; Adachi-Akahane, Satomi; Koizumi, Schuichi; Matsumoto, Masahiko; Sugiyama, Atsushi

    2010-12-01

    Milnacipran is a specific serotonin and norepinephrine reuptake inhibitor, which has been widely used against major depressive episodes. In this study, cardiovascular effects of milnacipran were assessed in comparison with those of a typical tricyclic antidepressant imipramine using the halothane-anesthetized dogs. Milnacipran (n = 6) or imipramine (n = 6) was intravenously administrated in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. Clinically relevant plasma concentrations were obtained after 0.1-1 mg/kg of milnacipran in this study, whereas therapeutic dose and plasma concentration of imipramine were reported to be similar to those of milnacipran. The low and middle doses of milnacipran hardly affected cardiohemodynamic or electrophysiological variables except that they slightly increased vascular tone and ventricular contraction, whereas same doses of imipramine delayed repolarization process without affecting the other variables. The high dose of both milnacipran and imipramine induced similar extent of negative chronotropic, inotropic and dromotropic effects together with vasoconstriction and repolarization delay. Thus, the effects of milnacipran may be more selective for cardiohemodynamics than for repolarization delay, whereas reverse will be true for imipramine, supporting lack of clinical report of patients with milnacipran-induced long QT syndrome unlike imipramine.

  14. [1+1 or 2x1? Another form of dual antidepressive mechanism of action].

    Science.gov (United States)

    Lakatos, László; Rihmer, Zoltán

    2005-09-01

    The primary aim of this review is to summarize the result of clinical trials comparing tricyclic antidepressants with first generation SSRIs, dual action (serotonergic and noradrenergic) agents like venlafaxine or mirtazapine with SSRIs and escitalopram with other SSRIs and venlafaxine. The review analyzes the relationship between the clinical efficacy and tolerability data and the mode of action. The clinical data suggest that multiple mode of action can substantially improve efficacy, however the relative risk of side-effects also increases if a drug affects multiple neurotransmitters. A new opportunity of development is the molecule of escitalopram introduced to the market some years ago. Its unique dual action on serotonergic transmission offers improved efficacy without compromising the favourable side-effect profile due to selectivity. Based on clinical trials escitalopram shows improved efficacy, faster onset of action and higher remission rates compared to first generation SSRIs. Remission rates with escitalopram are at least as high as with venlafaxine and escitalopram shows faster onset of action, earlier sustained remission and better tolerability. The good clinical efficacy data of escitalopram may be explained by its unique dual serotonergic effect on serotonin transporter protein.

  15. 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

  16. Effects of depression and antidepressant medications on hip fracture

    Science.gov (United States)

    Cheng, Bi-Hua; Chen, Pau-Chung; Yang, Yao-Hsu; Lee, Chuan-Pin; Huang, Ko-En; Chen, Vincent C.

    2016-01-01

    Abstract This study was conducted to investigate the effects of depression and antidepressant medications on hip fracture. The database of the Taiwan National Health Insurance with medical records of more than 1,000,000 individuals was searched for patients who had hip fracture with or without depression from 1998 to 2009. Patients with the following conditions were excluded: hip fracture due to cancer or traffic accidents, hip fracture that occurred before the diagnosis of depression, and use of antidepressants before the diagnosis of depression. A matched cohort of 139,110 patients was investigated, including 27,822 (17,309 females; 10,513 males) with depression and 111,288 (69,236 females; 42,052 males) without depression (1:4 randomly matched with age, sex, and index date). Among these patients, 232 (158 females and 74 males) had both hip fracture and depression, and 690 (473 females and 217 males) had hip fracture only. The Cox proportional-hazards regression method was used to determine the effect of depression on hip fracture. The hazard ratio (HR) for each clinical parameter was calculated after adjusting for confounders including sex, age, Charlson comorbidity index, urbanization, osteoporosis, and antidepressants. Results showed that patients with major depressive disorder had a 61% higher incidence of hip fracture than those without depression (HR 1.61, 95% confidence interval [CI] 1.19–2.18, P = 0.002). The risk of hip fracture for patients with less severe depressive disorder (dysthymia or depressive disorder, not otherwise specified) was not statistically higher than that of patients with no depression (HR 1.10, 95% CI = 0.91–1.34, P = 0.327). Among the patients with depression, females had a 49% higher incidence for hip fracture than males (HR 1.49, 95% CI 1.30–1.72, P < 0.001). The incidence of hip fracture also increased with age and Charlson comorbidity index scores. Analyses of both all (139,110) patients and only patients (27,822) with

  17. Potentials of Curcumin as an Antidepressant

    Directory of Open Access Journals (Sweden)

    S.K. Kulkarni

    2009-01-01

    Full Text Available Major depression, a debilitating psychiatric disorder, is predicted to be the second most prevalent human illness by the year 2020. Various antidepressants, ranging from monoamine oxidase inhibitors to recently developed dual reuptake inhibitors, are prescribed for alleviating the symptoms of depression. Despite the availability of these blockbuster molecules, approximately 30% of depressed patients do not respond to the existing drug therapies and the remaining 70% fails to achieve complete remission. Moreover, antidepressants are associated with a plethora of side effects and drug-drug/drug-food interactions. In this context, novel approaches are being tried to find more efficacious and safer drugs for the treatment of major depression. Curcumin is one such molecule that has shown promising efficacy in various animal models of major depression. Although the mechanism of the antidepressant effect of curcumin is not fully understood, it is hypothesized to act through inhibiting the monoamine oxidase enzyme and modulating the release of serotonin and dopamine. Moreover, evidences have shown that curcumin enhances neurogenesis, notably in the frontal cortex and hippocampal regions of the brain. The use of curcumin in clinics for the treatment of major depression is limited due to its poor gastrointestinal absorption. The present review attempts to discuss the pharmacological profile along with molecular mechanisms of the antidepressant effect of curcumin in animal models of depression. A need for clinical trials in order to explore the antidepressant efficacy and safety profile of curcumin is emphasized.

  18. Suicide by antidepressant intoxication identified at autopsy in Vienna from 1991-1997: the favourable consequences of the increasing use of SSRIs.

    Science.gov (United States)

    Frey, R; Schreinzer, D; Stimpfl, T; Vycudilik, W; Berzlanovich, A; Kasper, S

    2000-03-01

    In the area of Vienna, any person dying under questionable circumstances is examined at the Institute of Forensic Medicine, where the cause of death is determined by means of autopsy and chemical analysis. Our study on fatal intoxications was performed in the period between 1991 and 1997, when selective serotonin reuptake inhibitors (SSRIs) were establishing themselves on the market, reaching the top of prescription statistics. Tricyclic antidepressants (TCAs) were involved in 30 single- and 127 multiple-substance intoxications, with amitriptyline and doxepin being the most frequently used drugs. SSRIs were involved in five multiple-substance intoxications. The f-value, which refers to the number of deaths per million defined daily doses prescribed, was found to be significantly (Pantidepressants declined significantly (Pantidepressants did not coincide with an increased number of deaths caused by these drugs.

  19. Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist/inverse agonist properties.

    Science.gov (United States)

    Deiana, Valeria; Gómez-Cañas, María; Pazos, M Ruth; Fernández-Ruiz, Javier; Asproni, Battistina; Cichero, Elena; Fossa, Paola; Muñoz, Eduardo; Deligia, Francesco; Murineddu, Gabriele; García-Arencibia, Moisés; Pinna, Gerard A

    2016-04-13

    Previous studies have investigated the relevance and structure-activity relationships (SARs) of pyrazole derivatives in relation with cannabinoid receptors, and the series of tricyclic 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent CB2 receptor ligands. In the present study, novel 1,4-dihydroindeno[1,2-c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl or a cyclohexyl substituent were designed and synthesized to evaluate the influence of these structural modifications towards CB1 and CB2 receptor affinities. Among these derivatives, compound 15 (6-cyclopropyl-1-(2,4-dichlorophenyl)-N-(adamantan-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide) showed the highest CB2 receptor affinity (Ki = 4 nM) and remarkable selectivity (KiCB1/KiCB2 = 2232), whereas a similar affinity, within the nM range, was seen for the fenchyl derivative (compound 10: Ki = 6 nM), for the bornyl analogue (compound 14: Ki = 38 nM) and, to a lesser extent, for the aminopiperidine derivative (compound 6: Ki = 69 nM). Compounds 10 and 14 were also highly selective for the CB2 receptor (KiCB1/KiCB2 > 1000), whereas compound 6 was relatively selective (KiCB1/KiCB2 = 27). The four compounds were also subjected to GTPγS binding analysis showing antagonist/inverse agonist properties (IC50 for compound 14 = 27 nM, for 15 = 51 nM, for 10 = 80 nM and for 6 = 294 nM), and this activity was confirmed for the three more active compounds in a CB2 receptor-specific in vitro bioassay consisting in the quantification of prostaglandin E2 release by LPS-stimulated BV2 cells, in the presence and absence of WIN55,212-2 and/or the investigated compounds. Modelling studies were also conducted with the four compounds, which conformed with the structural requirements stated for the binding of antagonist compounds to the human CB2 receptor.

  20. Excessive mood elevation and behavioral activation with antidepressant treatment of juvenile depressive and anxiety disorders: a systematic review.

    Science.gov (United States)

    Offidani, Emanuela; Fava, Giovanni A; Tomba, Elena; Baldessarini, Ross J

    2013-01-01

    The prevalence, characteristics and implications of excessive arousal-activation in children and adolescents treated with antidepressants for specific illnesses have not been systematically examined. We compared reports of antidepressant trials (n = 6,767 subjects) in juvenile depressive (n = 17) and anxiety disorders (n = 25) for consensus-based indications of psychopathological mood elevation or behavioral activation. Rates of excessive arousal-activation during treatment with antidepressants were at least as high in juvenile anxiety (13.8%) as depressive (9.79%) disorders, and much lower with placebos (5.22 vs. 1.10%, respectively; both p antidepressant/placebo risk ratio for such reactions in paired comparisons was 3.50 (12.9/3.69%), and the meta-analytically pooled rate ratio was 1.7 (95% confidence interval: 1.2-2.2; both p ≤ 0.001). Overall rates for 'mania or hypomania', specifically, were 8.19% with and 0.17% without antidepressant treatment, with large drug/placebo risk ratios among depressive (10.4/0.45%) and anxiety (1.98/0.00%) disorder patients. Risks of excessive mood elevation during antidepressant treatment, including mania-hypomania, were much greater than with placebo, and similar in juvenile anxiety and depressive disorders. Excessive arousal-activation in children or adolescents treated with antidepressants for anxiety as well as depressive disorders calls for particular caution and monitoring for potential risk of future bipolar disorder. Copyright © 2013 S. Karger AG, Basel.

  1. Antidepressant use and salivary cortisol in depressive and anxiety disorders

    NARCIS (Netherlands)

    Manthey, Leonie; Leeds, Caroline; Giltay, Erik J.; van Veen, Tineke; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.

    Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic-pituitary-adrenal axis functioning, the alteration of which could be partially responsible for treatment

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  3. 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

  4. Antidepressant use and salivary cortisol in depressive and anxiety disorders

    NARCIS (Netherlands)

    Manthey, Leonie; Leeds, Caroline; Giltay, Erik J.; van Veen, Tineke; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.

    2011-01-01

    Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic-pituitary-adrenal axis functioning, the alteration of which could be partially responsible for treatment

  5. Prescription Pattern of Antidepressants for Children and Adolescents in Korea Based on Nationwide Data.

    Science.gov (United States)

    Chon, Myong Wuk; Lee, Jungsun; Chung, Seockhoon; Kim, Yangsik; Kim, Hyo Won

    2017-10-01

    Antidepressant prescription for youths has recently been on the increase. There is a growing concern over the increasing off-label usage of antidepressants. Current data on off-label antidepressant usage vary across countries and healthcare systems. Therefore, we examined the extent and pattern of antidepressant prescription for Korean children and adolescents using population-based data. Our data was retrieved from the Korean National Health Insurance Service National Sample Cohort of the year 2013. Among 0.2 million children and adolescents aged 6-18 years from the cohort, subjects who had received any antidepressant medication in the year 2013 were investigated for the prescribed medication, concomitant psychotropic medication, and the associated diagnosis. A total of 2,190 children and adolescents (boys, 55.4%) received antidepressant medication. The most common diagnosis was depressive disorders (n = 469, 21.4%), followed by attention-deficit/hyperactivity disorder (n = 442, 20.2%). Among the prescriptions (n = 3,370), escitalopram (n = 650, 24.1%) and fluoxetine (n = 553, 20.5%) were the two most frequently prescribed drugs. A majority of prescriptions (n = 2,039, 60.5%) included concomitant psychotropic agents, consisting of antipsychotics (n = 901, 26.7%), sedatives (n = 263, 26.3%), medication for attention-deficit/hyperactivity disorder (n = 822, 24.4%), and some others. Our study shows the prescription pattern of antidepressants for children and adolescents in Korea, of which a large proportion is off-label. The results call for close monitoring by clinicians treating this population. © 2017 The Korean Academy of Medical Sciences.

  6. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis.

    Science.gov (United States)

    Hannestad, Jonas; DellaGioia, Nicole; Bloch, Michael

    2011-11-01

    Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.

  7. 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.

  8. Bias in the reporting of harms in clinical trials of second-generation antidepressants for depression and anxiety : A meta-analysis

    NARCIS (Netherlands)

    de Vries, Ymkje Anna; Roest, Annelieke M.; Beijers, Lian; Turner, Erick H.; de Jonge, Peter

    2016-01-01

    Previous research has shown that reporting bias has inflated the apparent efficacy of antidepressants. We investigated whether apparent safety was also affected. We included 133 trials, involving 31,296 patients, of second-generation antidepressants for the treatment of major depressive disorder (MD

  9. Cost variation study of antidepressant drugs

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Shukla

    2016-10-01

    Conclusions: There is wide price variation of different brands of the same generic antidepressant drug in Indian market. Cost of a drug plays an important role in treatment of depression as it follows a long course and adherence to the treatment is related with drug cost. To decrease the wide cost variation among different brands of antidepressant drugs; it is high time to generate physician awareness about impact of cost effectiveness of drug regimen and for regulation of drug prices by the concerned agencies. [Int J Basic Clin Pharmacol 2016; 5(5.000: 1816-1821

  10. Synthesis of an Isoindoline-Annulated, Tricyclic Sultam Library via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS).

    Science.gov (United States)

    Ullah, Farman; Zang, Qin; Javed, Salim; Porubsky, Patrick; Neuenswander, Benjamin; Lushington, Gerald H; Hanson, Paul R; Organ, Michael G

    2012-01-01

    A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of an isoindoline-annulat-ed, tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy, is reported. This sequence involves a Heck reaction on vi-nylsulfonamides with batch microwave heating followed by a one-pot, sequential intramolecular aza-Michael cyclization/Boc-deprot-ection using MACOS. Subsequent cyclization with either 1,1'-carbonyldiimidazole or chloromethyl pivalate using MACOS provided an array of tricyclic sultams. This efficient three-step protocol requires only a few hours to produce the target sultams starting from simple starting materials. Using this strategy, a 38-member library of isoindoline-annulated sultams was generated in good to excellent overall yields (53-87%).

  11. Synthesis of an Isoindoline-Annulated, Tricyclic Sultam Library via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS)

    Science.gov (United States)

    Ullah, Farman; Zang, Qin; Javed, Salim; Porubsky, Patrick; Neuenswander, Benjamin; Lushington, Gerald H.

    2013-01-01

    A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of an isoindoline-annulat-ed, tricyclic sultam library, utilizing a Heck–aza-Michael (HaM) strategy, is reported. This sequence involves a Heck reaction on vi-nylsulfonamides with batch microwave heating followed by a one-pot, sequential intramolecular aza-Michael cyclization/Boc-deprot-ection using MACOS. Subsequent cyclization with either 1,1′-carbonyldiimidazole or chloromethyl pivalate using MACOS provided an array of tricyclic sultams. This efficient three-step protocol requires only a few hours to produce the target sultams starting from simple starting materials. Using this strategy, a 38-member library of isoindoline-annulated sultams was generated in good to excellent overall yields (53–87%). PMID:24244052

  12. 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…

  13. Prevalence of antidepressants and biosimilars in elite sport.

    Science.gov (United States)

    Machnik, M; Sigmund, G; Koch, A; Thevis, M; Schänzer, W

    2009-06-01

    The use of prescribed antidepressants by athletes has not been restricted in human sports since 2003, after the antidepressants bupropion and amineptine were removed from the list of prohibited substances. Recent awareness of antidepressants has been stimulated by reports from the media concerning possible misuse of antidepressants among healthy athletes. The prevalence of antidepressants has been monitored over the past ten years with screening procedures routinely used by WADA-accredited laboratories. The growth in antidepressant use among athletes peaked in 2007 and 2008 after a modest increase over the first eight years of this survey. Pharmacy prescriptions for antidepressants in Germany did not show a correlated growth during this period. The increasing variety of antidepressant medications has led to a continued increase in the diversity of antidepressant substances used by athletes and the 'normal' population. The number of different sports affected by the presence of antidepressants has increased in the past decade, especially in endurance sports. The predominance of female antidepressant users in the normal population was reflected in the athletes' group. We concluded from our results that the development of antidepressant prevalence in elite sports did not correlate with that among the general public in Germany.

  14. 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

  15. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.

    Science.gov (United States)

    de Mello Schier, Alexandre R; de Oliveira Ribeiro, Natalia P; Coutinho, Danielle S; Machado, Sergio; Arias-Carrión, Oscar; Crippa, Jose A; Zuardi, Antonio W; Nardi, Antonio E; Silva, Adriana C

    2014-01-01

    Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.

  16. A novel protocol for the facile construction of tetrahydroquinoline fused tricyclic frameworks via an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction.

    Science.gov (United States)

    Bakthadoss, Manickam; Vinayagam, Varathan

    2015-10-21

    An efficient method towards the synthesis of quinoline fused tricyclic compounds involving an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction utilizing Baylis-Hillman derivatives in good yields has been described for the first time. A highly functionalized tricyclic framework was created by forming two rings and two adjacent stereocentres through the formation of two N-C bonds, one C-C bond and one O-C bond in a highly regio and diastereoselective manner.

  17. Molecular modeling study of intercalation complexes of tricyclic carboxamides with d(CCGGCGCCGG)₂ and d(CGCGAATTCGCG)₂.

    Science.gov (United States)

    Varvaresou, Athanasia; Iakovou, Kriton

    2011-08-01

    Tricyclic dyes with different mesoatoms such as xanthenes (fluorescein, eosin) anthracenes and acridines (proflavine) approved by the Food and Drug Administration (FDA) for use in foods, pharmaceuticals and cosmetic preparations interact with DNA, and some of them do so through intercalation. Hyperchem 7.5, Spartan 04, Yasara 10.5.14 program packages and molecular modeling, molecular mechanics and dynamics techniques with the oligonucleotides d(CCGGCGCCGG)2 and d(CGCGAATTCGCG)2 were utilized in order to examine the mode of binding to DNA of a range of tricyclic carboxamides bearing N,N-dimethylaminoethyl side chain, i.e., 9-amino-DACA, anthracene, acridine-1-carboxamide, acridine-4-carboxamide (DACA), azacridine, phenazine, pyridoquinoxaline, oxopyridoquinoxaline, phenoxazine and xanthenone or N,N-dimethylaminobutyl moiety, i.e., phenazine and acridine. The bicyclic quinoline-8-carboxamide was also examined for comparison reasons. On the basis of our data, prerequisite for the interaction between protonated N,N-dimethylaminoethyl moiety and guanine is the formation of only one internal hydrogen bond between carboxamide and peri NH + in the case of 9-amino-DACA or peri N in the cases of DACA, azacridine, phenazine and pyridoquinoxaline. The presence of an additional internal hydrogen bond between oxygen carboxamide and protonated N,N-dimethylamino group in the cases of tricyclic systems bearing peri NH (phenoxazine) or O (xanthenone) group, prevents the interaction between side chain and guanine. Also, the formation of one internal hydrogen bond between oxygen carboxamide and protonated N,N-dimethylamino group inhibits the interaction between side chain and guanine in the case of acridine-1-carboxamide. Our findings are in accordance with previously reported results obtained from the kinetic studies of the binding of acridine and related tricyclic carboxamides to DNA.

  18. Discovery of Potent and Selective Tricyclic Inhibitors of Bruton’s Tyrosine Kinase with Improved Druglike Properties

    Science.gov (United States)

    2017-01-01

    In our continued effort to discover and develop best-in-class Bruton’s tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis. PMID:28626519

  19. Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice.

    Science.gov (United States)

    Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Poleszak, Ewa; Wlaź, Piotr

    2012-06-01

    The cholinergic theory of depression highlights the involvement of muscarinic acetylcholine receptors in the neurobiology of mood disorders. The present study was designed to investigate the effect of sildenafil, a phosphodiesterase type 5 inhibitor which exhibits cholinomimetic properties, alone and in combination with scopolamine in the forced swim test in mice. Moreover, we assessed the ability of sildenafil to modify the antidepressant activity of two tricyclic antidepressants with distinct cholinolytic activity, amitriptyline and desipramine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmacokinetic interaction between amitriptyline and sildenafil, brain and serum concentrations of amitriptyline were determined by HPLC. Sildenafil (1.25-20 mg/kg) as well as scopolamine (0.5 mg/kg) and its combination with sildenafil (1.25 mg/kg) did not affect the total immobility time duration. However, joint administration of scopolamine with sildenafil at doses of 2.5 and 5 mg/kg significantly reduced immobility time as compared to control group. Moreover, co-administration of scopolamine with sildenafil at the highest dose (5 mg/kg) significantly decreased immobility time as compared to scopolamine-treated group. Sildenafil (1.25, 2.5 and 5 mg/kg) significantly enhanced the antidepressant activity of amitriptyline (5 mg/kg). No changes in anti-immobility action of desipramine (20 mg/kg) in combination with sildenafil (5, 10 and 20 mg/kg) were observed. Sildenafil did not affect amitriptyline level in both brain and serum. In conclusion, the present study suggests that sildenafil may enhance the activity of antidepressant drugs which exhibit cholinolytic activity.

  20. How can we realize the promise of personalized antidepressant medicines?

    Science.gov (United States)

    Holsboer, Florian

    2008-08-01

    Personalized medication that is based on pharmacogenetic data has long been expected to improve the efficacy of treatments for neurological and psychiatric disorders, including depression. However, the complexity of the regulation of gene transcription and its interactions with environmental factors means that straightforward translation of individual genetic information into tailored treatment is unlikely. Nevertheless, when data from genomics, proteomics, metabolomics, neuroimaging and neuroendocrinology are used in combination, they could lead to the development of effective personalized antidepressant treatment that is based on both genotypes and biomarkers. This process will require many further steps and collaboration between basic and clinical neuroscience.

  1. Modulatory Effects of Antidepressant Classes on the Innate and Adaptive Immune System in Depression.

    Science.gov (United States)

    Eyre, H A; Lavretsky, H; Kartika, J; Qassim, A; Baune, B T

    2016-05-01

    Current reviews exploring for unique immune-modulatory profiles of antidepressant classes are limited by focusing mainly on cytokine modulation only and neglecting other aspects of the innate and adaptive immune system. These reviews also do not include recent comparative clinical trials, immune-genetic studies and therapeutics with unique neurotransmitter profiles (e. g., agomelatine). This systematic review extends the established literature by comprehensively reviewing the effects of antidepressants classes on both the innate and adaptive immune system. Antidepressants appear, in general, to reduce pro-inflammatory factor levels, particularly C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We caution against conclusions as to which antidepressant possesses the greater anti-inflammatory effect, given the methodological heterogeneity among studies and the small number of comparative studies. The effects of antidepressant classes on adaptive immune factors are complex and poorly understood, and few studies have been conducted. Methodological heterogeneity is high among these studies (e. g., length of study, cohort characteristics, dosage used and immune marker analysis). We recommend larger, comparative studies - in clinical and pre-clinical populations.

  2. Myricitrin induces antidepressant-like effects and facilitates adult neurogenesis in mice.

    Science.gov (United States)

    Meyer, Erika; Mori, Marco Aurélio; Campos, Alline Cristina; Andreatini, Roberto; Guimarães, Francisco Silveira; Milani, Humberto; de Oliveira, Rúbia Maria Weffort

    2017-01-01

    Myricitrin (MYR) is a natural flavonoid that inhibits nitric oxide (NO) transmission and has an atypical antipsychotic-like profile in animal models. Considering that several NO inhibitors exert antidepressant-like effects, the present study evaluated the antidepressant-like effect of MYR (3-30mg/kg) in the tail suspension test (TST). Because of the putative relationship between adult neurogenesis and antidepressant activity, we also assessed cell proliferation, survival, and differentiation in adult neurogenic niches, including the subgranular zone (SGZ) and subventricular zone (SVZ). Similar to the positive control imipramine (IMI; 10mg/kg), repeated treatment with 10mg/kg MIR but not acute treatment reduced immobility time in the TST, indicating an antidepressant-like effect. No effect on general motor activity was observed. Myricitrin also facilitated cell proliferation in the SGZ of the hippocampal dentate gyrus and SVZ. In the SGZ, MYR increased the number of doublecortin- and 5-bromo-2'-deoxyuridine/neuronal nuclei-positive cells. Our results suggest that MYR facilitates hippocampal neurogenesis, which might contribute to its antidepressant-like effect and atypical antipsychotic-like profile.

  3. DNA methylation and clinical response to antidepressant medication in major depressive disorder: A review and recommendations.

    Science.gov (United States)

    Lisoway, Amanda J; Zai, Clement C; Tiwari, Arun K; Kennedy, James L

    2017-01-04

    Antidepressant medications are the most common treatment for major depression and related disorders. Pharmacogenetic studies have demonstrated that response to these medications is associated with genetic variation. While these studies have been invaluable they have yet to explain why a significant number of patients do not respond to their initial medication. The epigenetic modification known as DNA methylation has recently been studied in the context of antidepressant treatment response. As such, the purpose of this article is to review the advances made in the relatively new field of pharmaco-epigenetics of antidepressant response. We included all published articles examining DNA methylation in association with antidepressant treatment response in Major Depressive Disorder from April 2006 to June 2016 using the PubMed, Medline, PsychInfo and Web of Science databases. At the present time, although original articles are limited, epigenetic modifications of SLC6A4, BDNF, and IL11 genes are showing promising results as biomarkers for prediction of antidepressant response. However, research methods and results are heterogeneous and additional studies are required before results are generalizable. At the end of this review we provide recommendations for study design and analytic approaches.

  4. Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant.

    Science.gov (United States)

    Zhu, Weili; Ding, Zengbo; Zhang, Yinan; Shi, Jie; Hashimoto, Kenji; Lu, Lin

    2016-12-01

    Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast-acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related side-effects. Future treatment strategies should consider using R-ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

  5. Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

    Science.gov (United States)

    Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

    2010-12-17

    Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects.

  6. Inhibition of Alzheimer's amyloid toxicity with a tricyclic pyrone molecule in vitro and in vivo.

    Science.gov (United States)

    Hong, Hyun-Seok; Rana, Sandeep; Barrigan, Lydia; Shi, Aibin; Zhang, Yi; Zhou, Feimeng; Jin, Lee-Way; Hua, Duy H

    2009-02-01

    Small beta-amyloid (Abeta) 1-42 aggregates are toxic to neurons and may be the primary toxic species in Alzheimer's disease (AD). Methods to reduce the level of Abeta, prevent Abeta aggregation, and eliminate existing Abeta aggregates have been proposed for treatment of AD. A tricyclic pyrone named CP2 is found to prevent cell death associated with Abeta oligomers. We studied the possible mechanisms of neuroprotection by CP2. Surface plasmon resonance spectroscopy shows a direct binding of CP2 with Abeta42 oligomer. Circular dichroism spectroscopy reveals monomeric Abeta42 peptide remains as a random coil/alpha-helix structure in the presence of CP2 over 48 h. Atomic force microscopy studies show CP2 exhibits similar ability to inhibit Abeta42 aggregation as that of Congo red and curcumin. Atomic force microscopy closed-fluid cell study demonstrates that CP2 disaggregates Abeta42 oligomers and protofibrils. CP2 also blocks Abeta fibrillations using a protein quantification method. Treatment of 5x familial Alzheimer's disease mice, a robust Abeta42-producing animal model of AD, with a 2-week course of CP2 resulted in 40% and 50% decreases in non-fibrillar and fibrillar Abeta species, respectively. Our results suggest that CP2 might be beneficial to AD patients by preventing Abeta aggregation and disaggregating existing Abeta oligomers and protofibrils.

  7. The in vitro effects of tricyclic drugs and dexamethasone on cellular respiration of malignant glioma.

    Science.gov (United States)

    Higgins, S C; Pilkington, G J

    2010-02-01

    In this investigation the effects of tricyclic drugs on cellular respiration were studied using the anaplastic astrocytoma cell line IPSB-18 by use of a Clark-type oxygen electrode which measured changes in cellular respiration rate (oxygen consumption), in a dose-response assay. The drugs investigated were clomipramine, norclomipramine, amitriptyline and doxepin. In addition, the combined effects of dexamethasone and clomipramine on cellular respiration were investigated. It was established that at lower concentrations (0.14 mM-0.5 mM) amitriptyline was the most potent inhibitor of cellular respiration. Previous studies have indicated that inhibition of cellular respiration is considered an indicator of apoptosis. Overall, it appeared that clomipramine and its metabolite norclomipramine were the most potent inhibitors of cellular respiration in glioma cells over the concentration range 0.5-0.9 mM. Dexamethasone was able to induce inhibition of cellular respiration both alone in glioma cells, and in combination with clomipramine, where it had an additive or synergistic effect, thereby increasing cell death. The extensive research currently ongoing and previously reported regarding the use of clomipramine as a potential antineoplastic agent aimed at targeting the mitochondria of gliomas is promising.

  8. Appetite - increased

    Science.gov (United States)

    Causes may include: Anxiety Certain drugs (such as corticosteroids, cyproheptadine, and tricyclic antidepressants) Bulimia (most common in women 18 to 30 years old) Diabetes mellitus (including gestational diabetes ) Graves disease ...

  9. Prenatal Antidepressants and Autism Spectrum Disorder

    Science.gov (United States)

    2014-09-01

    Autism Spectrum Disorder PRINCIPAL INVESTIGATOR...TYPE Annual 3. DATES COVERED 1Sept 2013-31Aug2014 4. TITLE AND SUBTITLE Prenatal Antidepressants and Autism Spectrum Disorder 5a...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT According to the CDC Autism Spectrum Disorder

  10. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

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

    2005-01-01

    options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics...

  11. 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...

  12. Physiological Bases of Bulimia, and Antidepressant Treatment.

    Science.gov (United States)

    Getzfeld, Andrew R.

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

  13. Potential antidepressant constituents of Nigella sativa seeds

    Directory of Open Access Journals (Sweden)

    Ehab S Elkhayat

    2016-01-01

    Full Text Available Background: Nigella sativa Linn. is well known seed in the Middle East, Asia, and the Far East as a natural remedy for many ailments and as a flavoring agent proclaimed medicinal usage dating back to the ancient Egyptians, Greeks, and Romans. An authentic saying of the Prophet Muhammad (Peace Be Upon Him about black seed is also quoted in Al-Bukhari. Objective: This study was carried out to evaluate the antidepressant effect and isolate the potential antidepressant constituents of the polar extract of N. sativa seeds. Materials and Methods: The antidepressant effect was evaluated through the immobility duration in tail suspension and forced swim tests (FSTs. Albino mice were orally treated with N. sativa polar extract and its RP-18 column chromatography fractions (50 and 100 mg/kg,. Results: The polar extract and two of its sub-fractions were significantly able to decrease the immobility time of mice when subjected to both tail suspension and FSTs, the effects are comparable to standard drug (Sertraline, 5 mg/kg. However, these treatments did not affect the number of crossings and rearing in the open field test. Phytochemical investigation of the two active fractions led to the isolation of quercetin-3-O-α-L-rhamnopyranoside 1, quercetin-7-O-β-D-gluco- pyranoside 2, tauroside E 3, and sapindoside B as the potential antidepressant constituents.

  14. Evaluating the tolerability of the newer antidepressants.

    Science.gov (United States)

    Dewan, M J; Anand, V S

    1999-02-01

    Given their equal efficacy, the choice of a specific antidepressant is largely influenced by side effect (SE) profiles. A number of new agents have recently become available. However, data directly comparing the side effects of these agents are scarce. As suggested by AHCPR guidelines, we used the 1998 Physicians' Desk Reference (PDR) to construct a comparison table using treatment emergent, placebo-adjusted incidence rates for the major (gastrointestinal, central nervous system, and sexual) side effects caused by nine antidepressants (fluoxetine, paroxetine, sertraline, fluvoxamine, nefazodone, bupropion SR, mirtazapine, venlafaxine XR, and citalopram). The results were tabulated to show the relative propensity of each drug to cause a particular side effect. Bupropion SR had the most favorable overall side-effect profile, and fluvoxamine the least favorable. However, there are several limitations in using the PDR to compare the newer antidepressants. Clinical studies directly comparing SEs of newer antidepressants are needed. Sexual SEs substantially affected total SE liability. A simplified summary table, with its advantages and some limitations, is not simple to construct. Pitfalls in this process are discussed.

  15. Effort-reward imbalance at work and the risk of antidepressant treatment in the Danish workforce

    DEFF Research Database (Denmark)

    Nielsen, Maj Britt D.; Madsen, Ida E. H.; Aust, Birgit;

    2016-01-01

    Background: Previous studies have shown that high effort-reward imbalance (ERI) at work is a risk factor for the onset of self-reported depressive symptoms. In this study, we examined whether ERI predicts risk of treatment with antidepressant medication in a representative sample of the Danish...... workforce. Methods: We linked survey data on ERI and covariates of 4541 participants from the Danish Work Environment Cohort Study 2000 with the Danish National Prescription Registry that includes all legally purchased prescription drugs at pharmacies in Denmark since 1995. Participants with a history...... of antidepressant treatment or with self-reported depressive symptoms at baseline were excluded. Using Cox proportional hazard analyses we examined the prospective association between ERI at baseline and incident antidepressant treatment while adjusting for potential confounders. Time of follow-up was 5 years...

  16. Effects of Depression and Serotonergic Antidepressants on Bone: Mechanisms and Implications for the Treatment of Depression.

    Science.gov (United States)

    Fernandes, Brisa S; Hodge, Jason M; Pasco, Julie A; Berk, Michael; Williams, Lana J

    2016-01-01

    Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care.

  17. How do antidepressants work? New perspectives for refining future treatment approaches.

    Science.gov (United States)

    Harmer, Catherine J; Duman, Ronald S; Cowen, Philip J

    2017-01-30

    Most currently available antidepressants target monoamine neurotransmitter function. However, a purely neurotransmitter-based explanation for antidepressant drug action is challenged by the delayed clinical onset of most agents and the need to explain how neurochemical changes reverse the many different symptoms of depression. Novel approaches to understanding of antidepressant drug action include a focus on early changes in emotional and social processing and the role of neural plasticity. In this Review, we discuss the ways in which these two different theories reflect different or complementary approaches, and how they might be integrated to offer novel solutions for people with depression. We consider the predictions made by these mechanistic approaches for the stratification and development of new therapeutics for depression, and the next steps that need to be made to facilitate this translation of science to the clinic.

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

    Directory of Open Access Journals (Sweden)

    Nadeem Siddiqui

    2011-01-01

    Full Text Available 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. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression.

  19. Increase in depression diagnoses and prescribed antidepressants among young girls. A national cohort study 2000-2013

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Science.gov (United States)

    Guan, Li-Ping; Liu, Bing-Yu

    2016-10-04

    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.

  1. 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

    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......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...

  2. Antidepressants for the treatment of depression in neurological disorders: a systematic review and meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Price, Annabel; Rayner, Lauren; Okon-Rocha, Ewa; Evans, Alison; Valsraj, Koravangattu; Higginson, Irene J; Hotopf, Matthew

    2011-08-01

    Despite the high prevalence of depression in people with neurological disorders, no previous study has sought to summarise existing evidence on the use of antidepressants in this population. A systematic review and meta-analysis was undertaken to determine whether antidepressants are more effective than placebo in the treatment of depression in neurological disorders, and whether any benefit is associated with improvement in function. Embase, Pubmed, Psycinfo and Cochrane trial registers were searched for randomised controlled trials (RCTs) comparing the efficacy of antidepressant and placebo in the treatment of depression in adults with a neurological disorder. 20 RCTs were included in the review, including patients with Parkinson's disease, multiple sclerosis, brain injury, epilepsy and stroke. Outcomes were analysed at four time points: 4-5 weeks, 6-8 weeks, 9-18 weeks and >18 weeks. The primary outcome was response to treatment at 6-8 weeks. The evidence favoured the use of antidepressants over placebo at all time points although pooled results were not statistically significant at all time points. At 6-8 weeks, antidepressant treatment was associated with a greater than twofold odds of remission (OR 2.23; 95% CI 1.54 to 3.23; number needed to treat=7). Fewer data were available for quality of life, and functional and cognitive outcomes, and there was little evidence of improvement with antidepressant treatment. Antidepressants are effective for the treatment of depression in patients with neurological disorders but the evidence for the efficacy of antidepressants in improving quality of life, and functional and cognitive outcomes is inconclusive.

  3. Antidepressant use in pregnancy: knowledge transfer and translation of research findings

    NARCIS (Netherlands)

    Einarson, Adrienne

    2015-01-01

    Background: Knowledge Transfer and Translation(KT) has become an important component in health care systems worldwide. Antidepressant use in pregnancy has become a controversial subject for a number of reasons, including differing interpretations of study results. An important question then arises

  4. Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors.

    Science.gov (United States)

    Ramirez, Karol; Sheridan, John F

    2016-10-01

    In order to relieve anxiety and depression accompanying stress, physicians resort to tricyclic antidepressants, such as imipramine. We had previously shown that imipramine reversed stress-induced social avoidance behavior, and down-regulated microglial activation 24days after stress cessation. To further characterize the effects of imipramine on stress induced neuroimmune dysregulation and associated changes in behavior, the aims of this study were to determine if imipramine 1) ameliorated stress-induced inflammation in the periphery and central nervous system, and 2) prevented stress related anxiety- and depressive-like behaviors. C57BL/6 mice were treated with imipramine (15mg/kg) in their drinking water, and exposed to repeated social defeat (RSD). Imipramine attenuated stress-induced corticosterone and IL-6 responses in plasma. Imipramine decreased the percentage of monocytes and granulocytes in the bone marrow and circulation. However, imipramine did not prevent splenomegaly, stress-related increased percentage of granulocytes in this organ, and the production of pro-inflammatory cytokines in the spleen, following RSD. Moreover, imipramine abrogated the accumulation of macrophages in the brain in mice exposed to RSD. Imipramine blocked neuroinflammatory signaling and prevented stress-related anxiety- and depressive-like behaviors. These data support the notion that pharmacomodulation of the monoaminergic system, besides exerting anxiolytic and antidepressant effects, may have therapeutic effects as a neuroimmunomodulator during stress.

  5. Antidepressant effects of Mentha pulegium in mice

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2016-09-01

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

  6. Neurogenesis and The Effect of Antidepressants

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    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. Relationship of dose to antidepressant prophylactic efficacy.

    Science.gov (United States)

    Peselow, E D; Difiglia, C; Fieve, R R

    1991-12-01

    We studied 75 patients on prophylactic antidepressants (imipramine or amitriptyline) to examine the effect of antidepressant dose on long-term prophylaxis of depression and to see whether lowering the dose during the prophylactic period affected subsequent relapse. There was no statistically significant difference in maintenance and prophylactic doses between the group that completed the 2 years free of a depressive episode, the group that had a depressive relapse and the group that dropped out of treatment before the end of the prophylactic period. However, the group that completed the 2 years free of a depressive episode had significantly less of a difference between the maintenance and prophylactic doses than the other 2 groups. Overall, 11/31 who remained on the same dose during the prophylactic period vs the maintenance period relapsed vs 17/25 who had their dose lowered during the prophylactic period vs the maintenance period. The difference was statistically significant.

  8. 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

  9. Antidepressant drugs: evaluation of price variation

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    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

  10. New Generation Antidepressants in Painful Diabetic Neuropathy

    OpenAIRE

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

    2011-01-01

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

  11. ANTI-DEPRESSANT POTENTIAL OF GHIYA

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    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.

  12. Antidepressants and Psychostimulants in Pediatric Populations

    Science.gov (United States)

    Goldsmith, Michelle; Singh, Manpreet; Chang, Kiki

    2012-01-01

    This article reviews the literature that examines whether exposure to psychostimulants or antidepressants precipitates or exacerbates manic symptoms, or decreases the age at onset of mania in pediatric populations. A PubMed search using relevant key words identified studies targeting five distinct clinical groups: (i) youth without a diagnosis of bipolar disorder (BD) at the time of exposure to psychostimulants; (ii) youth with a diagnosis of BD at the time of exposure to psychostimulants; (iii) youth without a diagnosis of BD at the time of exposure to antidepressants; (iv) youth with a diagnosis of BD at the time of exposure to antidepressants; and (v) youth who develop BD after exposure to these medications. In patients with attention-deficit hyperactivity disorder (ADHD), the risk for mania was found to be relatively low with the use of psychostimulants. For patients with BD and ADHD, effective mood stabilization is important prior to adding a stimulant. For children with depression and/or anxiety, the risk of antidepressant-induced mania (AIM) was generally low (<2%), but the risk of general ‘activation’ secondary to a selective serotonin reuptake inhibitor (SSRI) may be greater (2–10%). However, rates of AIM in specialty clinics appear to be much higher. SSRIs may be particularly problematic in specific populations, such as those with some symptoms of mania or a family history of BD, but the precise risk is unknown. There is no clear evidence that stimulants or SSRIs accelerate the natural course of BD development in overall samples, but in individual cases prescribers should proceed cautiously when using these agents in youth already at risk for developing BD, such as those with ADHD and mood dysregulation, a history of prior AIM, a history of psychosis, or a family history of BD. PMID:21692547

  13. Cost variation study of antidepressant drugs

    OpenAIRE

    Ajay Kumar Shukla; Parag Sharma

    2016-01-01

    Background: Depression and anxiety disorders are the most common mental illnesses, each affecting in excess of 10-15% of the population at some time in their lives. Approximately 10-15% of those with severe depression attempt suicide at some point of time. Thus, it is important that symptoms of depression be recognized and treated appropriately. Methods: The prices of 15 antidepressant drugs, available in 43 different formulations were analyzed. Costs of different brands of a particular ge...

  14. 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.

  15. Antidepressants and Suicide Risk: A Comprehensive Overview

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    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.

  16. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: a systematic review and meta-analysis.

    Science.gov (United States)

    Offidani, Emanuela; Guidi, Jenny; Tomba, Elena; Fava, Giovanni Andrea

    2013-01-01

    Placebo-controlled trials showed that both benzodiazepines (BDZ) and antidepressant drugs (AD) are effective in treating anxiety disorders. However, in the last years a progressive shift in the prescribing pattern from BDZ to newer AD has taken place. The aim of this systematic review and meta-analysis is to analyze whether controlled comparisons support such a shift. CINHAL, the Cochrane Library, MEDLINE, PubMed and Web of Science were searched from inception up to December 2012. A total of 22 studies met the criteria for inclusion. They were mostly concerned with tricyclic antidepressants (TCA; 18/22) and involved different anxiety disorders. In order to reduce clinical heterogeneity, only the 10 investigations that dealt with the comparison between TCA and BDZ in panic disorder were submitted to meta-analysis, whereas the remaining papers were individually summarized and critically examined. According to the systematic review, no consistent evidence emerged supporting the advantage of using TCA over BDZ in treating generalized anxiety disorder (GAD), complex phobias and mixed anxiety-depressive disorders. Indeed, BDZ showed fewer treatment withdrawals and adverse events than AD. In panic disorder with and without agoraphobia our meta-analysis found BDZ treatments more effective in reducing the number of panic attacks than TCA (risk ratio, RR = 1.13; 95% CI = 1.01-1.27). Furthermore, BDZ medications were significantly better tolerated than TCA drugs, causing less discontinuation (RR = 0.40; 95% CI = 0.20-0.57) and side effects (RR = 0.41; 95% CI = 0.34-0.50). As to newer AD, BDZ trials resulted in comparable or greater improvements and fewer adverse events in patients suffering from GAD or panic disorder. The change in the prescribing pattern favoring newer AD over BDZ in the treatment of anxiety disorders has occurred without supporting evidence. Indeed, the role and usefulness of BDZ need to be reappraised.

  17. Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012.

    Science.gov (United States)

    Bachmann, Christian J; Aagaard, Lise; Burcu, Mehmet; Glaeske, Gerd; Kalverdijk, Luuk J; Petersen, Irene; Schuiling-Veninga, Catharina C M; Wijlaars, Linda; Zito, Julie M; Hoffmann, Falk

    2016-03-01

    Following the FDA black box warning in 2004, substantial reductions in antidepressant (ATD) use were observed within 2 years in children and adolescents in several countries. However, whether these reductions were sustained is not known. The objective of this study was to assess more recent trends in ATD use in youth (0-19 years) for the calendar years 2005/6-2012 using data extracted from regional or national databases of Denmark, Germany, the Netherlands, the United Kingdom (UK), and the United States (US). In a repeated cross-sectional design, the annual prevalence of ATD use was calculated and stratified by age, sex, and according to subclass and specific drug. Across the years, the prevalence of ATD use increased from 1.3% to 1.6% in the US data (+26.1%); 0.7% to 1.1% in the UK data (+54.4%); 0.6% to 1.0% in Denmark data (+60.5%); 0.5% to 0.6% in the Netherlands data (+17.6%); and 0.3% to 0.5% in Germany data (+49.2%). The relative growth was greatest for 15-19 year olds in Denmark, Germany and UK cohorts, and for 10-14 year olds in Netherlands and US cohorts. While SSRIs were the most commonly used ATDs, particularly in Denmark (81.8% of all ATDs), Germany and the UK still displayed notable proportions of tricyclic antidepressant use (23.0% and 19.5%, respectively). Despite the sudden decline in ATD use in the wake of government warnings, this trend did not persist, and by contrast, in recent years, ATD use in children and adolescents has increased substantially in youth cohorts from five Western countries.

  18. The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf⁺/⁻ heterozygous null mice.

    Science.gov (United States)

    Lindholm, Jesse S O; Autio, Henri; Vesa, Liisa; Antila, Hanna; Lindemann, Lothar; Hoener, Marius C; Skolnick, Phil; Rantamäki, Tomi; Castrén, Eero

    2012-01-01

    Accumulating evidence suggests that biogenic amine-based antidepressants act, at least in part, via regulation of brain-derived neurotrophic factor (BDNF) signaling. Biogenic amine-based antidepressants increase BDNF synthesis and activate its signaling pathway through TrkB receptors. Moreover, the antidepressant-like effects of these molecules are abolished in BDNF deficient mice. Glutamate-based drugs, including the NMDA antagonist ketamine, and the AMPA receptor potentiator LY 451646, mimic the effects of antidepressants in preclinical tests with high predictive validity. In humans, a single intravenous dose of ketamine produces an antidepressant effect that is rapid, robust and persistent. In this study, we examined the role of BDNF in expression of the antidepressant-like effects of ketamine and an AMPA receptor potentiator (LY 451646) in the forced swim test (FST). Ketamine and LY 451646 produced antidepressant-like effects in the FST in mice at 45 min after a single injection, but no effects were observed one week after a single ketamine injection. As previously reported, the effects of imipramine in the forced swim test were blunted in heterozygous BDNF knockout (bdnf(+/-)) mice. However ketamine and LY 451646 produced similar antidepressant-like responses in wildtype and bdnf(+/-) mice. Neither ketamine nor LY 451646 significantly influenced the levels BDNF or TrkB phosphorylation in the hippocampus when assessed at 45 min or 7 days after the drug administration. These data demonstrate that under the conditions tested, neither ketamine nor the AMPA-potentiator LY 451656 activate BDNF signaling, but produce a characteristic antidepressant-like response in heterozygous bdnf(+/-) mice. These data indicate that unlike biogenic amine-based agents, BDNF signaling does not play a pivotal role in the antidepressant effects of glutamate-based compounds. This article is part of a Special Issue entitled 'Anxiety and Depression'.

  19. One-pot synthesis and UV-Visible absorption studies of novel tricyclic heterocycle tethered Xanthene-1,8-diones

    Indian Academy of Sciences (India)

    Thirumal Yempala; Balasubramanian Sridhar; Srinivas Kantevari

    2015-05-01

    A series of new tricyclic heterocyclic xanthene-1,8-diones tethered with chromophoric dibenzo [ , ]furan, dibenzo[ , ]thiophene and 9-methyl-9-carbazoles were synthesized through one-pot condensation of dibenzo[ , ]furan-2-carbaldehyde, dibenzo[ , ] thiophene-2-carbaldehyde and 9-methyl-9-carbazole-3-carbaldehyde with cyclic 1,3-dicarbonyls in the presence of recyclable PPA-SiOM2 catalyst under solvent-free conditions. Further, UV-Visible absorption properties of all the synthesized compounds were investigated in CHCl3, THF and acetonitrile.

  20. Citrinal A, a novel tricyclic derivative of citrinin,from an algicolous fungus Penicillium sp. i-1-1

    Institute of Scientific and Technical Information of China (English)

    Tian Jiao Zhu; Lin Du; Peng Fei Hao; Zhen Jian Lin; Qian Qun Gu

    2009-01-01

    Citrinal A (1), a novel tricyclic compound with a rare tetrahydro-2H-benzofuro[7-b] [1,4]dioxin-9(3H)-one skeleton, along with two known related compounds, citrinin (2) and 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (3) were isolated from an algicolous fungus Penicillium sp. i-1-1. The structure and stereochemistry of 1 were determined by comprehensive spectral and biogenic analysis. Its cytotoxic effects on the A-549 and HL-60 cell lines were evaluated.

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

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    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.

  2. Synthesis and evaluation of iodine-123 labelled tricyclic tropanes as radioligands for the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Quinlivan, Mitchell; Mattner, Filomena; Papazian, Vahan; Zhou, Jia; Katsifis, Andrew; Emond, Patrick; Chalon, Sylvie; Kozikowski, Alan; Guilloteau, Denis; Kassiou, Michael E-mail: mkassiou@med.usyd.edu.au

    2003-10-01

    The tricyclic tropane analogues (1S,3S,6R,10S)-(Z)-10-(benzoyloxymethyl)-9-(3-chloro-4-iodobenzylidene)-7 -azatricyclo[4.3.1.0{sup 3,7}]decane, 1, and (1S,3S,6R,10S)-(Z)-9-(3-chloro-4-iodobenzylidene)-7-azatricyclo[4.3.1.0{sup 3,7}] = decane-10-carboxylic acid methyl ester, 2, have been shown to be potent and selective serotonin transporter (SERT) ligands. They possess nanomolar affinity for the SERT (Ki = 0.06 nM and 1.8 nM respectively) and are suitable for radiolabelling using iodine-123. In the present study we prepared [{sup 123}I]1 and [{sup 123}I]2 from the appropriate tributylstannane precursors using acidic media with chloramine-T as the oxidising agent. The radiochemical yield obtained for [{sup 123}I]1 varied between 50-60% while for [{sup 123}I]2 the range was 65-80%. Both radioligands were obtained with radiochemical purity > 97% and specific activity estimated to be > 185 GBq/{mu}mol. The biodistribution of [{sup 123}I]1 demonstrated low degree of brain penetration at 5 min (0.14%ID/g) with a homogenous distribution. The radioactivity cleared quickly from all brain regions with no preferential localization. In comparison, [{sup 123}I]2 demonstrated on average a higher brain uptake at 5 min (0.5%ID/g). However the distribution of radioactivity was homogenous and cleared to levels similar to [{sup 123}I]1 at 1 hr post-injection. Pre-administration of citalopram failed to show any significant inhibition of [{sup 123}I]2 uptake in the rat brain. The high lipophilicity of 1 and 2 (HPLC-derived log P{sub 7.4} values of 6.41 and 4.25 respectively) and in vivo metabolism, seen by high thyroid uptake would explain the absence of any specific binding observed in the rat brain. In view of these results [{sup 123}I]1 and [{sup 123}I]2 do not appear to be suitable radioligands for in vivo studies of the SERT.

  3. Concise synthesis and anti-HIV activity of pyrimido[1,2-c][1,3]benzothiazin-6-imines and related tricyclic heterocycles.

    Science.gov (United States)

    Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka

    2012-09-07

    3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (PD 404182) is a virucidal heterocyclic compound active against various viruses, including HCV, HIV, and simian immunodeficiency virus. Using facile synthetic approaches that we developed for the synthesis of pyrimido[1,2-c][1,3]benzothiazin-6-imines and related tricyclic derivatives, the parallel structural optimizations of the central 1,3-thiazin-2-imine core, the benzene part, and the cyclic amidine part of PD 404182 were investigated. Replacement of the 6-6-6 pyrimido[1,2-c][1,3]benzothiazin-6-imine framework with 5-6-6 or 6-6-5 derivatives led to a significant loss of anti-HIV activity, and introduction of a hydrophobic group at the 9- or 10-positions improved the potency. In addition, we demonstrated that the PD 404182 derivative exerts anti-HIV effects at an early stage of viral infection.

  4. Benzodiazepines and adequacy of initial antidepressant treatment for depression.

    Science.gov (United States)

    Pfeiffer, Paul N; Ganoczy, Dara; Zivin, Kara; Valenstein, Marcia

    2011-06-01

    In short-term efficacy studies, coprescription of a benzodiazepine improves first-month adherence and response to antidepressant treatment. We used Veterans Health Administration data to examine the impact of coprescribed benzodiazepines on initial antidepressant adherence in routine clinical practice and the risks of long-term benzodiazepine use, abuse, and dependence. Our study population was 43,915 Veterans Health Administration patients diagnosed with depression and started on an antidepressant between October 2006 and September 2007. Using logistic regression, adjusting for demographic and clinical covariates, we predicted the likelihood that patients received antidepressant treatment for an adequate duration (90 days), with our primary independent variable of interest being receipt of a benzodiazepine on the same day as the start of the antidepressant. We also assessed the frequency and characteristics of patients whose benzodiazepine use persisted for 1 year or who were diagnosed with anxiolytic abuse or dependence after receiving combined treatment. The adjusted probability of receiving antidepressant treatment of adequate duration was 42.4% for patients who received a benzodiazepine with their initial antidepressant compared with 39.3% for patients initially treated with an antidepressant alone (P benzodiazepines for at least 1 year, and 0.7% were diagnosed with anxiolytic abuse or dependence. Anxiolytic abuse or dependence, but not long-term benzodiazepine use, was associated with other substance use disorders. These findings should be considered by clinicians when assessing the individual risks and benefits of combining a benzodiazepine with antidepressant treatment.

  5. Antidepressants triggering suicidal ideation: An area of concern

    Directory of Open Access Journals (Sweden)

    Himali Rajgadhi

    2016-01-01

    Full Text Available This is a report of four cases of possible suicidal ideation with the use of antidepressants in Indian population. The patients presented to emergency department of a tertiary care hospital with attempted suicide. All of them were prescribed at least one antidepressant. The association of increased suicidal attempts/ideation with antidepressant drugs themselves has been reported in the West, but data in the Indian population are lacking. Antidepressants are widely used not only for treatment of depression but also many other psychiatric illnesses; it is yet unclear whether suicidal ideation is because of these drugs or the progression of the disease. Hence, careful prescribing of these medicines is warranted.

  6. Simple, Rapid and Sensitive UV-Visible Spectrophotometric Method for Determination of Antidepressant Amitriptyline in Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    Pankaj Soni

    2013-01-01

    Full Text Available The paper describes a new and simple approach for spectrophotometric determination of tricyclic antidepressant drug amitriptyline. Enhancement of the colour intensity of the Fe(III-SCN− complex on addition of the drug amitriptyline forms the basis of the proposed method. The value of molar absorptivity of the Fe(III-SCN− amitriptyline ion pair complex in terms of the drug lies in the range of (2.82–3.36 × 103 L·mol−1·cm−1 at the absorption maximum 460 nm. The detection limit of the method was 0.3 μg·mL−1. The slope, intercept, and correlation coefficients for the present method were found to be 0.008, 0.002, and +0.998, respectively. The effect of analytical variables on the determination of the drug and the composition of the complex are discussed in the paper. The method is applicable in the determination of amitriptyline in pharmaceutical preparations.

  7. Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K as anti-malarial agents

    Science.gov (United States)

    Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

    2017-06-01

    The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

  8. A Combination of Stop-and-Go and Electro-Tricycle Laser Scanning Systems for Rural Cadastral Surveys

    Directory of Open Access Journals (Sweden)

    Liang Zhong

    2016-09-01

    Full Text Available Over the past decade, land-based laser scanning technologies have been actively studied and implemented, in response to the need for detailed three-dimensional (3D data about our rural and urban environment for topographic mapping, cadastral mapping, and other street-level features, which are difficult and time consuming to measure by other instruments. For rural areas in China, the complex terrain and poor planning limit the applicability of this advanced technology. To improve the efficiency of rural surveys, we present two SSW (Shoushi and SiWei laser scanning systems for rapid topographic mapping: stop-and-go and electro-tricycle laser scanning systems. The objective of this paper is to evaluate whether laser scanning data collected by the developed SSW systems meet the accuracy requirements for rural homestead mapping. We investigated the performance of the two laser scanning systems on Ma’anshan Village, a small, typical village in Hubei Province, China. To obtain full coverage of the village, we fused the stop-and-go and electro-tricycle laser scanning data. The performance of the developed SSW systems is described by the results of building contours extracted from the fused data against the established building vector map.

  9. Design, synthesis and biological evaluation of tricyclic diterpene derivatives as novel neuroprotective agents against ischemic brain injury.

    Science.gov (United States)

    Wang, Ying-Ying; Gao, Yuan-Xue; Gao, Wei; Xu, Yuan; Xu, Ya-Zhou; Wang, Yun-Jie; Chang, Sai; Yu, Li-Gang; Zhang, Lu-Yong; Liao, Hong; Yang, Lian-Fang; Pang, Tao; Qiu, Wen-Wei

    2015-10-20

    Lead compound 7 has neuroprotective effects, and it was discovered by screening a small synthetic natural product-like (NPL) library. Based on the lead, a series of tricyclic diterpene derivatives was designed and synthesized, and their neuroprotective effects were further evaluated against glutamate-, oxygen and glucose deprivation (OGD)- and nutrient deprivation-induced neuronal injury using cell-based assays. To our delight, most of these synthetic compounds exhibited increased neuroprotective effects and blood-brain barrier (BBB) permeability without cellular toxicity. The most potent compound, compound 30, showed significantly improved neuroprotection against neuronal injury in primary neurons. Furthermore, compound 30 exhibited remarkable neuroprotection in transient middle cerebral artery occlusion (tMCAO) rats by reducing their infarct sizes and neurological deficit scores. A mechanistic exploration using in vitro and in vivo experiments showed that the neuroprotection of these compounds was at least partly mediated by improving the levels of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein. Therefore, these tricyclic diterpene derivatives could be used as promising leads for the development of a new type of neuroprotective agents against ischemic brain injury.

  10. Antidepressant-like effect of endomorphin-1 and endomorphin-2 in mice.

    Science.gov (United States)

    Fichna, Jakub; Janecka, Anna; Piestrzeniewicz, Mariola; Costentin, Jean; do Rego, Jean-Claude

    2007-04-01

    Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) are two recently isolated mu-opioid selective peptides with a potent antinociceptive activity, involved in a number of physiological processes, including food intake, vasomotricity, sexual behavior, as well as neuroendocrine and cardiorespiratory functions. The neuroanatomical distribution of endomorphins prompted us to study their antidepressant activity in two animal behavioral models of depression: forced-swimming and tail-suspension tests. In both tests, the intracerebroventricular (i.c.v.) injection of either endomorphin-1 or endomorphin-2 significantly decreased the duration of immobility, interpreted as an expression of 'behavioral despair', which could be related to the depression syndrome. These effects of endomorphins did not result from the stimulation of the animal motor activity. We have also demonstrated that the antidepressant-like effect of endomorphins was antagonized by the universal opioid antagonist, naloxone and the mu-opioid receptor selective antagonist, beta-funaltrexamine. In contrast, this effect was not antagonized by delta- and kappa-opioid receptor selective antagonists, naltrindole and nor-binaltorphimine, respectively. The results of the present study demonstrate that endomorphin-1 and endomorphin-2 produce potent antidepressant-like effects after i.c.v. injection in mice. We may suggest that endomorphins and the mu-opioid receptors might be involved in the physiopathology of depressive disorders, and that the endomorphinergic system could serve as a novel target for the development of antidepressant drugs.

  11. Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments.

    Science.gov (United States)

    Leuchter, Andrew F; Hunter, Aimee M; Krantz, David E; Cook, Ian A

    2015-05-01

    Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD.

  12. Antidepressant use and associated factors among the elderly: the Bambuí Project

    Directory of Open Access Journals (Sweden)

    Adriano Roberto Tarifa Vicente

    2015-12-01

    Full Text Available Abstract This study examined the factors associated with antidepressant use among community-dwelling elderly individuals. Data collected from the Bambuí Project, a population-based study on aging and health with a cohort of 1,606 elderly individuals, were used. Gender, age, education, marital status, household income and cohabitation status were the sociodemographic characteristics investigated. Health conditions included self-reported health, number of chronic diseases, depressive symptoms, cognitive impairment and functional disability. Poisson regression with robust variance was used to test associations and to estimate prevalence ratios with 95% confidence intervals. The prevalence of antidepressant use was 8.4%. After multivariate analysis, antidepressant use was associated with the female gender (PR = 2.96; 95%CI 1.82-4.81, being single or divorced (PR = 0.48; 95%CI 0.25-0.91, cognitive impairment (PR = 0.44; 95%CI 0.24-0.84 and worse self-reported health (poor/very poor (PR=1.86; 95%CI 1.11-3.10. The results are similar to those observed in several other studies conducted in higher-income countries and suggest that self-reported health in the elderly population of Bambuí is a key factor in the decision to use antidepressants.

  13. Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments

    Science.gov (United States)

    Leuchter, Andrew F.; Hunter, Aimee M.; Krantz, David E.; Cook, Ian A.

    2015-01-01

    Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD. PMID:25809789

  14. Are antidepressants effective in quality of life improvement among children and adolescents? A systematic review.

    Science.gov (United States)

    Stevanovic, Dejan; Tadic, Ivana; Knez, Rajna

    2014-04-01

    There is some evidence indicating that psychotropic medications might lead to health-related quality of life (QOL) improvements among children and adolescents with psychiatric disorders. The aim of this systematic review is to assess evidence regarding whether antidepressant treatment improves QOL among children and adolescents with depressive or anxiety disorders. A comprehensive search resulted in 5 clinical trials to be included in this review: 4 trials with major depressive disorder (MDD) and 1 trial with social anxiety disorder (SAD). In one MDD trial, fluoxetine combined with cognitive behavior therapy (CBT) significantly improved QOL compared to fluoxetine or CBT alone (effect sizes were 0.53 and 0.69, respectively). In 2 combined trials, sertraline alone significantly improved QOL among adolescents with MDD (effect size was 0.29), but not among children with MDD. Essentially, it was observed that antidepressants in these trials had minor positive effects on QOL improvement, which were lower than their potential to improve depressive symptoms. Although fluoxetine with CBT or sertraline monotherapy were shown to have some potential to improve QOL, this systematic review found inconclusive evidence that antidepressant treatments improve QOL among children and adolescents with depressive or anxiety disorders. More research is required, considering that QOL is currently under-evaluated in clinical trials with antidepressants among children and adolescents and available trials have limited methodological quality when reporting QOL data.

  15. 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 ant...

  16. 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...

  17. 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.

  18. Imaging TMS: antidepressant mechanisms and treatment optimization.

    Science.gov (United States)

    Dubin, Marc

    2017-04-01

    With the antidepressant efficacy of Transcranial Magnetic Stimulation well-established by several meta-analyses, there is growing interest in its mechanism of action. TMS has been shown to engage, and in some cases, normalize functional connectivity and neurotransmitter levels within networks dysfunctional in the depressed state. In this review, I will suggest candidate biomarkers, based on neuroimaging, that may be predictive of response to TMS. I will then review the effects of TMS on networks and neurotransmitter systems involved in depression. Throughout, I will also discuss how our current understanding of response predication and network engagement may be used to personalize treatment and optimize its efficacy.

  19. Association between bystander cardiopulmonary resuscitation and redeemed prescriptions for antidepressants and anxiolytics in out-of-hospital cardiac arrest survivors.

    Science.gov (United States)

    Bundgaard, Kristian; Hansen, Steen M; Mortensen, Rikke Nørmark; Wissenberg, Mads; Hansen, Malta; Lippert, Freddy; Gislason, Gunnar; Køber, Lars; Nielsen, Jimmi; Torp-Pedersen, Christian; Rasmussen, Bodil Steen; Kragholm, Kristian

    2017-06-01

    This study aimed to examine rates of redeemed prescriptions of antidepressants and anxiolytics, used as markers for cerebral dysfunction in out-of-hospital cardiac arrest (OHCA) survivors, and examine the association between bystander CPR and these psychoactive drugs. We included all 30-day survivors of OHCA in Denmark between 2001 and 2011, who had not redeemed prescriptions for antidepressants or anxiolytics in the last six months prior to OHCA. Main outcome measures were redeemed prescriptions of antidepressants and anxiolytics within one year after OHCA. Among 2,001 30-day survivors, 174 (8.6% died and 12.0% redeemed a first prescription for an antidepressant and 8.2% for an anxiolytic drug within one year after arrest. The corresponding frequencies for redeemed prescribed drugs among age- and sex-matched population controls were 7.5% and 5.2%, respectively. Among survivors who received bystander CPR, prescriptions for antidepressants and anxiolytics were redeemed in 11.1% [95% CI 9.2-13.3%] and 6.3% [95% CI 4.9-8.0%] of the cases, respectively, versus 17.2% [95% CI 13.9-21.1%] and 13.4% [95% CI 10.5-17.0%], respectively, among patients who had not received bystander CPR. Adjusted for age, sex, year of arrest, comorbidity, witnessed status and socioeconomic status, bystander CPR was associated with significant reductions in redeemed prescriptions for antidepressants, Hazard Ratio (HR) 0.71 [95% CI 0.52-0.98], P=0.031; and anxiolytics, HR 0.55 [95% CI 0.38-0.81], P=0.002. Relative to no bystander CPR, redeemed prescriptions for antidepressants and anxiolytics were significantly lower among 30-day survivors of OHCA who received bystander CPR, suggesting a cerebral dysfunction-lowering potential of bystander CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Occurrence of antidepressant residues in the sewage-impacted Vistula and Utrata rivers and in tap water in Warsaw (Poland).

    Science.gov (United States)

    Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

    2014-06-01

    Antidepressants, even at low concentrations, can reveal some adverse effects on aquatic life due to disturbing homeostasis throughout the central and peripheral nervous system both in vertebrates and invertebrates. To date there have not been any reports regarding the presence of these pharmaceuticals in surface and tap waters in Eastern Europe. Therefore the aim of this study was to determine the presence of 21 antidepressant pharmaceuticals at specific points of the main Polish river - the Vistula, a smaller river of the Warsaw region - the Utrata, as well as in tap water samples of Warsaw. Samples were collected twice at one month intervals and analysed using solid-phase extraction (SPE) technique coupled with the liquid chromatography-electrospray ionisation-tandem mass spectrometer (LC-MS/MS) method operated under the multiple reaction monitoring mode (MRM). This is the first study where active compounds such as moclobemid or trazodone in the environment have been investigated. Environmental risk assessment of antidepressants in Poland was estimated on the basis of annuals sale data extracted from the NFZ (Narodowy Fundusz Zdrowia-National Health Service) base of reimbursed pharmaceuticals(1). Predicted environmental concentration (PEC) of target pharmaceuticals were compared with their measured concentration (MEC). Moreover, the application of the EMEA/CHMP guideline for environmental risk assessment of the antidepressants was discussed. The highest concentration of antidepressants was observed in the small river Utrata. In tap water only trace amounts of antidepressants including citalopram (up to 1.5ng/l), mianserin (up to 0.9ng/l), sertraline (<3.1ng/l), moclobemid (up to 0.3ng/l) and venlafaxine (up to 1.9ng/l) were detected. However this highlights their inadequate elimination in the drinking waste treatment facility. The presence of antidepressants in drinking water and the aquatic environment could have long-term effects even at low exposure level

  1. St. John's wort and antidepressant drug interactions in the elderly.

    Science.gov (United States)

    Lantz, M S; Buchalter, E; Giambanco, V

    1999-01-01

    There is increasing interest in and use of the herbal preparation St. John's wort. Hypericin, the major active ingredient, has many psychoactive properties. The agent is sold in the US as a nutritional supplement and is recommended for numerous conditions, including depression, anxiety, insomnia, and inflammation. We report a series of five cases of clinically diagnosed central serotonergic syndrome among elderly patients who combined prescription antidepressants with St. John's wort. Older adults are large consumers of both over-the-counter and prescription medications. They are particularly vulnerable to interactions between medications and products sold as nutritional or herbal supplements. St. John's wort requires further evaluation due to potential for drug interactions with central nervous system agents and for more definitive therapeutic indications.

  2. Neuroplasticity and major depression, the role of modern antidepressant drugs

    OpenAIRE

    Serafini, Gianluca

    2012-01-01

    The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to pro...

  3. 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

  4. 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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  7. 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

  8. Antidepressant-like effects of the extract from Cimicifuga foetida L.

    Science.gov (United States)

    Ye, Liang; Hu, Zhengping; Du, Guangying; Zhang, Jianzhao; Dong, Qiuju; Fu, Fenghua; Tian, Jingwei

    2012-12-18

    Cimicifuga foetida L., a traditional Chinese medicine, has been developed for the treatment of perimenopausal symptoms including depression in China (Brand name: XIMINGTING(®), XMT). The primary active constituents are believed to be the triterpene glycosides. Nevertheless, there are no studies about the antidepressant-like effects of XMT in rodents. The present study aimed to evaluate antidepressant-like effects of XMT. Antidepressant-like activity of XMT was studied using forced swimming test (FST) and tail suspension test (TST) in female mice, as well as chronic mild stress (CMS) procedure in female rats. In addition, 5-hydroxytryptophan (5-HTP)-induced head-twitch test and yohimbine toxicity potentiation test in female mice were conducted to propose the possible serotonergic or noradrenergic mechanisms in the antidepressant-like effects of XMT. In mice, XMT was administrated acutely and for 7 consecutive days (20, 40 and 80 mg/kg/day, p.o.); and in rats for 28 consecutive days (10, 20 and 40 mg/kg/day, p.o.). XMT significantly reduced immobility duration in FST and TST without affecting locomotor activity, increased swimming and climbing durations in FST, and enhanced 5-HTP-induced head-twitch response while did not affect yohimbine-induced lethality in female mice. XMT also normalized the inhibition of sucrose intake and decreased the levels of plasma adrenocorticotropic hormone and serum corticosterone and adrenal gland weight in CMS-treated female rats. These data indicate XMT processes antidepressant-like properties in rodents, which could be related to its serotonergic and noradrenergic activation and normalization of the hypothalamic-pituitary-adrenal axis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. 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.

  10. 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.

  11. Increased use of antidepressants at the end of life

    DEFF Research Database (Denmark)

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

    2007-01-01

    BACKGROUND: The new antidepressants are generally effective and safe for older people, but may have serious side-effects. The use has been rapidly increasing, but focus on upper age groups has been limited. The pattern of antidepressant use as death approaches has never been analysed. OBJECTIVE......: To analyse the use of antidepressants among individuals aged 65 years and above with respect to time trends, age and proximity to death. DESIGN: Population-based prescription study. SETTING: The County of Funen, Denmark, 1992-2004 (approximately 470,000 inhabitants). RESULTS: The 1-year prevalence...... 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...

  12. ANTIDEPRESSANT ACTIVITY OF HYDROALCOHOLIC EXTRACT OF ZINGIBER OFFICINALE

    Directory of Open Access Journals (Sweden)

    Singh Rudra Pratap

    2012-02-01

    Full Text Available The present study was design to evaluate the effect of Zingiber officinale hydro-alcoholic extract as well as its interaction with conventional anxiolytic and antidepressant drugs using tail suspension test and forced swim test (FST and to evaluate the possible mechanisms involved in its actions. The rhizomes of ginger were collected and authenticated. Extraction of dried rhizomes was carried out using soxhlet apparatus to obtain its Hydro alcoholic extract. The extract of Zingiber officinale showed the significant antidepressant activity comparable to the standard drug. The oral administration of Zingiber officinale extract at 150 mg/ kg and 300 mg/kg respectively as compared to the control treated group showed an antidepressant activity comparable to that of standard drug. The antidepressant effects of Zingiber officinale extract seem to be mainly associated with the activation of dopamineergic system and possess potential anxiolytic and antidepressant activities.

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

    Science.gov (United States)

    2013-02-01

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

  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

    BACKGROUND: Adherence to antidepressant medication is a challenging clinical issue, which reduces treatment efficacy: 30-60% of all patients commencing treatment with antidepressants are estimated to stop taking the medication within the first 12 weeks. Patients' personal beliefs about depression...... 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 psychosocial and biology...... and antidepressants are regarded as central influences on adherence. OBJECTIVES: The aim was to gain detailed insight into patients' personal accounts of depression and use of antidepressant medication and to relate these accounts to the patients' self-reported level of adherence. METHODS: In-depth, qualitative...

  15. Antidepressant utilization after hospitalization with depression

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Antidepressant (AD) therapy is recommended for patients 4-12 months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD the...... only minor impact on these associations. CONCLUSION: Immigrants seem less likely to receive the recommended AD treatment after hospitalization with depression. This may indicate a need for a better understanding of the circumstances of this vulnerable group.......BACKGROUND: Antidepressant (AD) therapy is recommended for patients 4-12 months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD...... therapy after discharge and 2) early AD discontinuation. METHODS: A cohort of immigrants from non-Western countries (n = 132) and matched Danish-born residents (n = 396) discharged after first admission with moderate to severe depression between 1 January 1996 and 31 May 2008 was followed in the Danish...

  16. Antidepressant drug discovery in the postgenomic era.

    Science.gov (United States)

    Holsboer, F

    2001-10-01

    The progress made in genome research raises the question whether the new knowledge bases that have emerged may also lead to better antidepressants. The past has seen many remarkable improvements over traditional drugs, but not a real breakthrough. More recently hypothesis-driven research in depression has focussed upon stress-hormone regulation as a possible target, but validation of new drugs is not yet in sight. In parallel, we see an upsurge of systematic unbiased research in a biotechnology-driven drug discovery effort. This research can only lead to results if clinical research adapts to these new demands by phenotyping depressed patients not only according to psychopathological characteristics but also by utilising functional (e.g. neuroendocrine, neuropsychological, neurophysiological, neuroimaging and clinical drug response) data that are to be correlated with data from genotyping. To achieve the goal of genotype/phenotype-based differential therapy, large-scale efforts with regards to both patient samples and genotyping capacities are needed. In the long term, increasingly detailed patient information, if translated into specific pharmacological treatments, will lead to customized drugs and thus to a partial fragmentation of the antidepressant market. Concurrently, the improved genotyping/phenotyping efforts will also lead to more widely applicable drugs that promise to avoid side effects and refractoriness and also to hasten the time to onset of action. Once these goals are achieved notorious undertreatment of depression may come to an end.

  17. Antidepressant utilization after hospitalization with depression

    DEFF Research Database (Denmark)

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

    2014-01-01

    Background: Antidepressant (AD) therapy is recommended for patients 4-12months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD ther...... treatment after hospitalization with depression. This may indicate a need for a better understanding of the circumstances of this vulnerable group.......Background: Antidepressant (AD) therapy is recommended for patients 4-12months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD...... therapy after discharge and 2) early AD discontinuation. Methods: A cohort of immigrants from non-Western countries (n=132) and matched Danish-born residents (n=396) discharged after first admission with moderate to severe depression between 1 January 1996 and 31 May 2008 was followed in the Danish...

  18. A Facile Protocol for the Construction of Tricyclic Framework Tetrahydrobenzo-4-nitrobenzenesulfonate, 4-methylbenzenesulfonate and [1,8] naphthyridine Substituents from Methyl δ-Lactam

    Directory of Open Access Journals (Sweden)

    Shireen Mohammed

    2015-12-01

    Full Text Available Retraction of: A Facile Protocol for the Construction of Tricyclic Framework Tetrahydrobenzo-4-nitrobenzenesulfonate, 4-methylbenzenesulfonate and [1,8] naphthyridine Substituents from Methyl δ-Lactam/, http://dx.doi.org/10.13005/ojc/310435 by Shireen Mohammed and Maher Khalid as it was published by them without the permission of their supervisor.

  19. Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study

    OpenAIRE

    Hughes, S; Cohen, D.; Jaggi, R

    2014-01-01

    Objective: To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies. Design: Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles. Setting: Clinicalstudyresults.org, sponsored by Pharmaceutical Research and M...

  20. Use of antidepressive agents as a possibility in the management of periodontal diseases: A systematic review of experimental studies.

    Science.gov (United States)

    Muniz, Francisco Wilker Mustafa Gomes; Melo, Iracema Matos; Rösing, Cassiano Kuchenbecker; de Andrade, Geanne Matos; Martins, Ricardo Souza; Moreira, Maria Mônica Studart Mendes; Carvalho, Rosimary de Sousa

    2017-09-01

    Antidepressant agents have anti-inflammatory functions that could be interesting as adjuvants in periodontal therapy. The aim of the present study was to analyze the effect of antidepressive drugs in the management of periodontal disease. The MEDLINE, Scopus, Embase, LILACS, and SciELO databases were searched. To be included, the studies had to be experimental studies; randomized, controlled; double-blinded; or blinded studies. A total of 565 articles were initially searched, of which five were selected for the systematic review. All studies used rats, and three different drugs were evaluated: tianeptine, venlafaxine, and fluoxetine. Two of these studies evaluated the effect of antidepressive agents in rats submitted to both ligature-induced periodontitis and depression models, showing that depressive rats had greater alveolar bone loss (ABL). Only the venlafaxine study was not able to find any significant ABL reduction in the group that used this antidepressive drug. The other four studies showed statistically-significant differences, favoring the group with the antidepressant agent. Treatments that are able to modulate the brain-neuroendocrine-immune system could be used as an adjuvant to periodontal disease management. However, studies on humans and animals are scarce, limiting the conclusion of a positive effect in the present systematic review. © 2017 John Wiley & Sons Australia, Ltd.

  1. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

    Science.gov (United States)

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold

    2016-01-01

    Summary Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

  2. Synthesis and structure-activity relationship studies of novel [6,6,5] tricyclic oxazolidinone derivatives as potential antibacterial agents.

    Science.gov (United States)

    Xue, Tao; Ding, Shi; Guo, Bin; Chu, Wenjing; Wang, Hui; Yang, Yushe

    2015-01-01

    In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate 2. In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6,6,5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds 54, 58, 59 and 63. In vitro liver microsomal stability was further evaluated and the results manifested that compounds 54 and 58 were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics.

  3. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

    Directory of Open Access Journals (Sweden)

    Jakub Saadi

    2016-06-01

    Full Text Available Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II back to palladium(0 which is apparently achieved by the present triethylamine.

  4. Design and synthesis of tricyclic tetrahydroquinolines as a new series of nonsteroidal selective androgen receptor modulators (SARMs).

    Science.gov (United States)

    Nagata, Naoya; Miyakawa, Motonori; Amano, Seiji; Furuya, Kazuyuki; Yamamoto, Noriko; Inoguchi, Kiyoshi

    2011-03-15

    Some tricyclic tetrahydroquinolines (THQs) were found to have the potential of a new series of nonsteroidal selective androgen receptor modulators (SARMs). Compound 5b was first designed and synthesized under our hypothesis based on a four-point pharmacophoric requirement of the 3-carbonyl, 18-methyl, 17-hydroxyl, and 13-quaternary carbon groups of dihydrotestosterone (DHT). It was revealed that this compound exhibits not only a strong androgen receptor (AR) agonistic activity (EC(50)=9.2 nM) but also the highest selectivity in binding affinity to AR among the steroid hormone receptors. Furthermore, this compound showed a weak virilizing effect with retention of the desired anabolic effect as compared with DHT in vivo.

  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. Naphthyridine-Benzoazaquinolone: Evaluation of a Tricyclic System for the Binding to (CAG)n Repeat DNA and RNA.

    Science.gov (United States)

    Li, Jinxing; Sakata, Akihiro; He, Hanping; Bai, Li-Ping; Murata, Asako; Dohno, Chikara; Nakatani, Kazuhiko

    2016-07-05

    The expansion of CAG repeats in the human genome causes the neurological disorder Huntington's disease. The small-molecule naphthyridine-azaquinolone NA we reported earlier bound to the CAG/CAG motif in the hairpin structure of the CAG repeat DNA. In order to investigate and improve NA-binding to the CAG repeat DNA and RNA, we conducted systematic structure-binding studies of NA to CAG repeats. Among the five new NA derivatives we synthesized, surface plasmon resonance (SPR) assay showed that all of the derivatives modified from amide linkages in NA to a carbamate linkage failed to bind to CAG repeat DNA and RNA. One derivative, NBzA, modified by incorporating an additional ring to the azaquinolone was found to bind to both d(CAG)9 and r(CAG)9 . NBzA binding to d(CAG)9 was similar to NA binding in terms of large changes in the SPR assay and circular dichroism (CD) as well as pairwise binding, as assessed by electron spray ionization time-of-flight (ESI-TOF) mass spectrometry. For the binding to r(CAG)9 , both NA and NBzA showed stepwise binding in ESI-TOF MS, and NBzA-binding to r(CAG)9 induced more extensive conformational change than NA-binding. The tricyclic system in NBzA did not show significant effects on the binding, selectivity, and translation, but provides a large chemical space for further modification to gain higher affinity and selectivity. These studies revealed that the linker structure in NA and NBzA was suitable for the binding to CAG DNA and RNA, and that the tricyclic benzoazaquinolone did not interfere with the binding.

  7. Inhibitory and lytic effects of phenothiazine derivatives and related tricyclic neuroleptic compounds, on Entamoeba histolytica HK9 and HM1 trophozoites.

    Science.gov (United States)

    Ondarza, R N; Hernández, E; Iturbe, A; Hurtado, G

    2000-08-01

    It has been shown previously that tricyclic neuroleptics like clomipramine and chlorpromazine have lethal effects on Leishmania donovani and L. major, and other studies indicate that the phenothiazine inhibitors of trypanothione reductase are potential anti-trypanosomal and anti-leishmanial drugs. With this in mind and our original observation on the presence of trypanothione in Entamoeba histolytica HK9, we examined the possible inhibitory effects of various phenothiazine and tricyclic derivatives on this human parasite. We found that drugs like clomipramine (KD002), the most potent in vitro inhibitor of trypanothione reductase among 30 tricyclic compounds tested, at 25 microM after 24 h of culture under aerobic conditions, caused a substantial decrease in the number of E. histolytica HK9 trophozoites, from approx. 15 x 10(6) to 5.37 x 10(6) cells, and at 100 microM to 0.8 x 10(6) cells. A substantial inhibitory effect on cell proliferation could also be demonstrated with metronidazol (used clinically against amoebiasis). Under similar experimental conditions other tricyclic and phenothiazine derivatives (OFKs), designed originally to inhibit the trypanothione reductase of trypanosomatides, had an inhibitory effect of 16 to 95%. For comparison, similar results were obtained using clomipramine and a phenothiazine derivative (OFK006) with Trypanosoma cruzi and Crithidia luciliae, except that with the latter the inhibitory effect of clomipramine was less dramatic. Experiments comparing two E. histolytica strains showed that normal cell proliferation under anaerobiosis was higher in strain HK9 than in HM1, which is highly virulent, but that metronidazol and clomipramine were less effective against HM1. Two other drugs tested, diphenydramine (KD005) and a phenothiazine derivative (OFK008), also had significant but lower inhibitory effects on both strains. The inhibitory activity on cell proliferation and the lytic effects on this human parasite by the tricyclic

  8. Differential effects of antidepressants escitalopram versus lithium on Gs alpha membrane relocalization

    OpenAIRE

    Donati, Robert J.; Schappi, Jeffrey; Czysz, Andrew H; Jackson, Alexander; Mark M Rasenick

    2015-01-01

    Background Plasma membrane localization can play a significant role in the ultimate function of certain proteins. Specific membrane domains like lipid rafts have been shown to be inhibitory domains to a number of signaling proteins, including Gsα, and chronic antidepressant treatment facilitates Gs signaling by removing Gsα form lipid rafts. The intent of this study is to compare the effects of the selective serotnin reuptake inhibitor, escitalopram, with that of the mood stabilizing drug, li...

  9. [Drug dependence on benzodiazepines and antidepressants].

    Science.gov (United States)

    Verbanck, P

    2009-09-01

    Since years, the concepts of drug abuse and drug dependence changed, due to new knowledge coming from the neurosciences. Specifically, the role of a brain structure called "reward circuit" was emphasized. Therefore, the diagnosis criteria for abuse and dependence on drugs are presently defined mostly from a behavioral point of view: both in animal models and in clinical situations, it was stressed the importance of drug-seeking behavior and of the loss of control of the consumption. The occurrence of a pharmacological dependence is in fact of concern for only some of addictive drugs. According to these new criteria, dependence on benzodiazepines or antidepressants is certainly not frequent, even if withdrawal manifestations can occur after a long-term exposition. Furthermore, it is important to keep in mind the risk for non-medical use of benzodiazepines in persons with illicit drug use.

  10. Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression.

    Science.gov (United States)

    Kayser, Sarah; Bewernick, Bettina H; Grubert, Christiane; Hadrysiewicz, Barbara L; Axmacher, Nikolai; Schlaepfer, Thomas E

    2011-05-01

    Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy. Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist. Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials.

  11. Why antidepressants are not antidepressants: STEP-BD, STAR*D, and the return of neurotic depression.

    Science.gov (United States)

    Ghaemi, S Nassir

    2008-12-01

    The widely held clinical view of 'antidepressants' as highly effective and specific for the treatment of all types of depressive disorders is exaggerated. This sobering conclusion is supported by recent findings from the NIMH-sponsored STEP-BD and STAR*D projects. Antidepressants have limited short-term efficacy in unipolar depressive disorders and less in acute bipolar depression; their long-term prophylactic effectiveness in recurrent unipolar major depression remains uncertain, and is doubtful in recurrent bipolar depression. These limitations may, in part, reflect the excessively broad concept of major depression as well as unrealistic expectations of universal efficacy of drugs considered 'antidepressants.' Treatment-refractory depression may reflect failure to distinguish depressive conditions, particularly bipolar disorder, that are inherently less responsive to antidepressants. Antidepressants probably should be avoided in bipolar depression, mixed manic-depressive states, and in neurotic depression. Expectations of antidepressants for specific types of patients with symptoms of depression or anxiety require critical re-evaluation. A revival of the concept of neurotic depression would make it possible to identify patients with mild-to-moderate, chronic or episodic dysthymia and anxiety who are unlikely to benefit greatly from antidepressants. Diagnostic criteria for a revival of the concept of neurotic depression are proposed.

  12. Antidepressant, psychostimulant, and nootropic effects of major and trace element composition.

    Science.gov (United States)

    Afanasieva, O G; Suslov, N I; Shilova, I V

    2013-06-01

    The antidepressant, psychostimulant, and nootropic effects of a composition of major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc sulfate were studied on the models of behavioural despair (Porsolt test) and conditioned passive avoidance test. The preparation was found to shorten the immobilization time in the Porsolt test and promote retention of the conditioned passive avoidance. The most pronounced psychostimulant effect of the substance was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the preparation was found at a dose of 93.6 mg/kg.

  13. What is the role of sedating antidepressants, antipsychotics, and anticonvulsants in the management of insomnia?

    Science.gov (United States)

    McCall, Catherine; McCall, W Vaughn

    2012-10-01

    Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.

  14. 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...... 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...

  15. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  16. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusion

  17. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.

    Directory of Open Access Journals (Sweden)

    Irving Kirsch

    2008-02-01

    Full Text Available BACKGROUND: Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. METHODS AND FINDINGS: We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug-placebo difference scores. Drug-placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. CONCLUSIONS: Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

  18. Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

    Science.gov (United States)

    Kirsch, Irving; Deacon, Brett J; Huedo-Medina, Tania B; Scoboria, Alan; Moore, Thomas J; Johnson, Blair T

    2008-01-01

    Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. PMID:18303940

  19. Increase in depression diagnoses and prescribed antidepressants among young girls. A national cohort study 2000-2013.

    Science.gov (United States)

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

    2017-07-01

    To analyse trends in depression diagnoses and antidepressant use according to age and gender. Nationwide cohort study including all women and men of 10-49 years living in Denmark during 2000-2013. The Psychiatric Registry and Prescription Registry provided data on depression diagnoses and antidepressant medication, respectively. Incidence rates as well as 1-year prevalence rates were calculated. The incidence and 1-year prevalence rates of depression diagnoses increased during 2000-2013. The women/men rates were 2.0 for both 1-year prevalence of depressions diagnoses and antidepressant use. For adolescent girls, the absolute increase was 3 per 1000 for depression diagnoses and 8 per 1000 for first use of antidepressants, compared to boys who had an increase of 1.1 and 3 per 1000, respectively. Before puberty, boys and girls had almost the same incidence rates of both depression diagnoses and antidepressant use throughout the period. After puberty, girls had significantly higher incidence rates than boys, and experienced during the study period a steeper increase than boys. According to age, the girls/boys incidence rate ratio of a depression diagnosis increased from 0.8 in the 10-11 year age group to 2.7 at age 12-19 years and hereafter decreased with increasing age to 1.5 at age 45-49. Depression diagnosed and first use of antidepressants increased more for girls of 12-19 years than for boys during 2000-2013, and the incidences were similar for girls and boys before puberty, but higher after puberty for girls.

  20. GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus.

    Science.gov (United States)

    Liang, Zihong; Bai, Shunjie; Shen, Peng; Hu, Qingchuan; Wang, Xingfa; Dong, Meixue; Wang, Wei; Li, Juan; Cheng, Ke; Zhang, Shuxiao; Zou, Dezhi; Han, Yu; Wang, Haiyang; Xie, Peng

    2016-11-01

    Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have antidepressant activity based on previous behavioral and biochemical analyses. However, because GBE contain many constituents, the mechanisms underlying this suggested antidepressant activity are unclear. Here, we investigated the antidepressant-like effects of diterpene ginkgolides (DG), an important class of constituents in GBE, and studied their effects in the mouse hippocampus using a GC-MS-based metabolomics approach. Mice were randomly divided into five groups and injected daily until testing with 0.9% NaCl solution, one of three doses of DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and tail suspension (TST) tests were then performed to evaluate depressive-like behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg) treatment also shortened immobility time in the TST, suggestive of antidepressant-like effects. Significant differences in the metabolic profile in the DG (12.18mg/kg) compared with the control or VLX group indicative of an antidepressant-like effect were observed using multivariate analysis. Eighteen differential hippocampal metabolites were identified that discriminated the DG (12.18mg/kg) and control groups. These biochemical changes involved neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid metabolism, energy metabolism, and kynurenic acid, providing clues to the therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant-like activities in mice and shed light on the biological mechanisms underlying the effects of diterpene ginkgolides on behavior, providing an important drug candidate for the treatment of depression.

  1. Genome-wide association studies in pharmacogenomics of antidepressants.

    Science.gov (United States)

    Lin, Eugene; Lane, Hsien-Yuan

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Doctors must prescribe antidepressants based on educated guesses due to the fact that it is unmanageable to predict the effectiveness of any particular antidepressant in an individual patient. With the recent advent of scientific research, the genome-wide association study (GWAS) is extensively employed to analyze hundreds of thousands of single nucleotide polymorphisms by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been utilized to investigate the determinants of antidepressant response to therapy. In this study, we reviewed GWAS studies, their limitations and future directions with respect to the pharmacogenomics of antidepressants in MDD.

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

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen

    2014-01-01

    is challenging. The best available method is through epidemiological studies. During the past decade use of antidepressants during pregnancy has been associated with negative birth outcomes, such as congenital malformations. In spite of a considerable number of studies on the subject, the data are still...... 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...... saw a halving in prevalence of antidepressant exposure and a steep increase after delivery. Our analyses showed an association between being in treatment with an SSRI and congenital malformations. However, this increased risk was also found for women pausing treatment before pregnancy. We conclude...

  3. Antidepressants in Pregnancy Tied to Slight Increase in Autism

    Science.gov (United States)

    ... 167328.html Antidepressants in Pregnancy Tied to Slight Increase in Autism But difference in risk is quite ... to rule out the possibility that depression itself increases the risk of autism, rather than the medications ...

  4. Substituted urea derivatives: a potent class of antidepressant agents.

    Science.gov (United States)

    Perveen, Shahnaz; Mustafa, Sana; Khan, Muhammad A; Dar, Ahsana; Khan, Khalid M; Voelter, Wolfgang

    2012-05-01

    A series of fourteen (14) N-nitrophenyl-N'-(alkyl/aryl)urea and symmetrical 1,3-disubstituted urea derivatives were synthesized and evaluated for their antidepressant activity in mice. Among them, N-(4-nitrophenyl)-N'-(1'-phenylethyl)urea (1), demonstrated profound antidepressant property as reflected by significant reduction in the immobility time (89.83%), whereas compounds 2-6 showed activity values between 36 to 59% which were also larger than the standard phenelzine. Compounds 7-9 were less effective in reducing the immobility period of mice 26.20 to 31.01%). This variable magnitude of antidepressant activity appears to be related to the position of the nitro group to the parent molecules 1, 2, and 8. Compound 1 with the nitro group at para position showed to be the most effective antidepressant. However, the activity declined, if the nitro is attached to ortho and meta positions.

  5. Antidepressant-associated sexual dysfunction: impact, effects, and treatment

    Directory of Open Access Journals (Sweden)

    Agnes Higgins

    2010-09-01

    Full Text Available Agnes Higgins, Michael Nash, Aileen M LynchSchool of Nursing and Midwifery Studies, Trinity College Dublin, Dublin, IrelandAbstract: 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 delayed orgasm, to erection or delayed ejaculation problems. There are a number of case reports of sexual side effects, such as priapism, painful ejaculation, penile anesthesia, loss of sensation in the vagina and nipples, persistent genital arousal and nonpuerperal lactation in women. The focus of this article is to explore the incidence, pathophysiology, and treatment of antidepressant iatrogenic sexual dysfunction.Keywords: depression, antidepressant, iatrogenic sexual dysfunction, SSRI, SNRI

  6. Antidepressant treatment of depression in rural nursing home residents.

    Science.gov (United States)

    Kerber, Cindy Sullivan; Dyck, Mary J; Culp, Kennith R; Buckwalter, Kathleen

    2008-09-01

    Under-diagnosis and under-treatment of depression are major problems in nursing home residents. The purpose of this study was to determine antidepressant use among nursing home residents who were diagnosed with depression using three different methods: (1) the Geriatric Depression Scale, (2) Minimum Data Set, and (3) primary care provider assessments. As one would expect, the odds of being treated with an antidepressant were about eight times higher for those diagnosed as depressed by the primary care provider compared to the Geriatric Depression Scale or the Minimum Data Set. Men were less likely to be diagnosed and treated with antidepressants by their primary care provider than women. Depression detected by nurses through the Minimum Data Set was treated at a lower rate with antidepressants, which generates issues related to interprofessional communication, nursing staff communication, and the need for geropsychiatric role models in nursing homes.

  7. Use of antidepressant serotoninergic medications and cardiac valvulopathy: a nested case–control study in the health improvement network (THIN) database

    Science.gov (United States)

    Lapi, Francesco; Nicotra, Federica; Scotti, Lorenza; Vannacci, Alfredo; Thompson, Mary; Pieri, Francesco; Mugelli, Niccolò; Zambon, Antonella; Corrao, Giovanni; Mugelli, Alessandro; Rubino, Annalisa

    2012-01-01

    AIMS To quantify the risk of cardiac valvulopathy (CV) associated with the use of antidepressant serotoninergic medications (SMs). METHODS We conducted a case–control study nested in a cohort of users of antidepressant SMs selected from The Health Improvement Network database. Patients who experienced a CV event during follow-up were cases. Cases were ascertained in a random sample of them. Up to 10 controls were matched to each case by sex, age, month and year of the study entry. Use of antidepressant SMs during follow-up was defined as current (the last prescription for antidepressant SMs occurred in the 2 months before the CV event), recent (in the 2–12 months before the CV event) and past (>12 months before the CV event). We fitted a conditional regression model to estimate the association between use of antidepressant SMs and the risk of CV by means of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Sensitivity analyses were conducted to test the robustness of our results. RESULTS The study cohort included 752 945 subjects aged 18–89 years. Throughout follow-up, 1663 cases (incidence rate: 3.4 per 10 000 person-years) of CV were detected and were matched to 16 566 controls. The adjusted OR (95% CI) for current and recent users compared with past users of antidepressant SMs were 1.16 (0.96–1.40) and 1.06 (0.93–1.22), respectively. Consistent effect estimates were obtained when considering cumulative exposure to antidepressant SMs during follow-up. CONCLUSIONS These results would suggest that exposure to antidepressant SMs is not associated with an increased risk of CV. PMID:22356433

  8. Why is mechanism of action important in antidepressant treatment?

    Science.gov (United States)

    Schwartz, Thomas L

    2016-05-01

    Antidepressants are one of the most common treatment strategies for patients diagnosed with major depressive disorder (MDD). However, antidepressant medications have different mechanisms of action that can theoretically and in practice affect how patients respond. Clinicians should assess their patients' symptoms and response to medication at every visit to determine whether or not the treatment is fully effective. Here, follow the case of Maria, a 42-year-old teacher who is experiencing her first depressive episode.

  9. Challenging Received Wisdom: Antidepressants and the Placebo Effect

    Science.gov (United States)

    Kirsch, Irving

    2008-01-01

    This article explores the reaction when an article challenging received wisdom is published and covered extensively by the media (1). The article in question was a meta-analysis of antidepressant clinical trials indicating that for most patients, difference between drug and placebo was not clinically significant. Reactions ranged from denial that the effects of antidepressants are so small to criticisms of the clinical trials that were analyzed. Each of these reactions is explored and countered. PMID:19148327

  10. 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...

  11. Antidepressant-associated sexual dysfunction: impact, effects, and treatment

    OpenAIRE

    Agnes Higgins; Michael Nash; Lynch, Aileen M.

    2010-01-01

    Agnes Higgins, Michael Nash, Aileen M LynchSchool of Nursing and Midwifery Studies, Trinity College Dublin, Dublin, IrelandAbstract: 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 prev...

  12. Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice.

    Science.gov (United States)

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

    2008-03-14

    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 were similar to responses of antidepressant drug-treated animals. When tested under conditions where locomotor activity was not altered, exercising mice also showed reduced anxiety compared to sedentary control mice. In situ hybridization analysis showed that BDNF mRNA was increased in specific subfields of hippocampus after wheel running. We chose one paradigm, the FST, in which to investigate a functional role for brain-derived neurotrophic factor (BDNF) in the behavioral response to exercise. We tested mice heterozygous for a deletion of the BDNF gene in the FST after wheel-running. Exercising wild-type mice showed the expected antidepressant-like behavioral response in the FST but exercise was ineffective in improving FST performance in heterozygous BDNF knockout mice. A possible functional contribution of a BDNF signaling pathway to FST performance in exercising mice was investigated using the specific MEK inhibitor PD184161 to block the MAPK signaling pathway. Subchronic administration of PD184161 to exercising mice blocked the antidepressant-like behavioral response seen in vehicle-treated exercising mice in the FST. In summary, chronic wheel-running exercise in mice results in antidepressant-like behavioral changes that may involve a BDNF related mechanism similar to that hypothesized for antidepressant drug treatment.

  13. Antidepressant use during pregnancy and psychiatric disorders in offspring

    DEFF Research Database (Denmark)

    Liu, Xiaoqin; Agerbo, Esben; Ingstrup, Katja G

    2017-01-01

    disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased...

  14. Obtained effect size as a function of sample size in approved antidepressants: a real-world illustration in support of better trial design.

    Science.gov (United States)

    Gibertini, Michael; Nations, Kari R; Whitaker, John A

    2012-03-01

    The high failure rate of antidepressant trials has spurred exploration of the factors that affect trial sensitivity. In the current analysis, Food and Drug Administration antidepressant drug registration trial data compiled by Turner et al. is extended to include the most recently approved antidepressants. The expanded dataset is examined to further establish the likely population effect size (ES) for monoaminergic antidepressants and to demonstrate the relationship between observed ES and sample size in trials on compounds with proven efficacy. Results indicate that the overall underlying ES for antidepressants is approximately 0.30, and that the variability in observed ES across trials is related to the sample size of the trial. The current data provide a unique real-world illustration of an often underappreciated statistical truism: that small N trials are more likely to mislead than to inform, and that by aligning sample size to the population ES, risks of both erroneously high and low effects are minimized. The results in the current study make this abstract concept concrete and will help drug developers arrive at informed gate decisions with greater confidence and fewer risks, improving the odds of success for future antidepressant trials.

  15. A model of placebo response in antidepressant clinical trials.

    Science.gov (United States)

    Rutherford, Bret R; Roose, Steven P

    2013-07-01

    Placebo response in clinical trials of antidepressant medications is substantial and has been increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to trial failures and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for major depressive disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. In this review, the authors examine contributors to placebo response in antidepressant clinical trials and propose an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact designed to enhance treatment response.

  16. Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis.

    Science.gov (United States)

    Amick, Halle R; Gartlehner, Gerald; Gaynes, Bradley N; Forneris, Catherine; Asher, Gary N; Morgan, Laura C; Coker-Schwimmer, Emmanuel; Boland, Erin; Lux, Linda J; Gaylord, Susan; Bann, Carla; Pierl, Christiane Barbara; Lohr, Kathleen N

    2015-12-08

    What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January 1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, -0.38, -2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings. Second generation antidepressants and CBT

  17. 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.

  18. Pharmacoscintigraphic evaluation of potential of lipid nanocarriers for nose-to-brain delivery of antidepressant drug.

    Science.gov (United States)

    Alam, M Intakhab; Baboota, Sanjula; Ahuja, Alka; Ali, Mushir; Ali, Javed; Sahni, Jasjeet K; Bhatnagar, Aseem

    2014-08-15

    Efficacy of antidepressants relies upon their continued presence at the site of action (brain) over a prolonged period of time. The BBB restricts the access of antidepressants to the brain on oral as well as intravenous administration. Direct delivery (by-passing the BBB) of antidepressant drugs can increase the CSF concentration with concomitant reduction in dose and side effects. Intranasal administration of nanostructured lipid carriers (NLC) containing antidepressant drug circumvent the BBB and maintain the prolonged release at the site of action. The aim of the present study was to evaluate the enhancement in brain uptake of NLC containing duloxetine (DLX) after intranasal administration. Duloxetine loaded NLC (DLX-NLC) was evaluated pharmacoscintigraphically for drug targeting potential (DTP), drug targeting efficiency (DTE) and biodistribution studies in different organs including brain. The radiolabeling efficiency of DLX and DLX-NLC was found to be 98.41 ± 0.96 and 98.87 ± 0.82 after 30 min, respectively. The biodistribution studies exhibited higher percentage of radioactivity/g for DLX-NLC formulations in brain as compared with the DLX. The higher DTP (86.80%) and DTE (757.74%) suggested that DLX-NLC formulation has a better brain targeting efficiency than DLX solution (DTP=65.12%; DTE=287.34%) when administered intranasally. Moreover, the intranasal administration exhibited about 8-times higher concentration of DLX in brain when compared with the intravenous administration of DLX solution. The intranasal NLC containing DLX can be employed as an effective method for the treatment of depression. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Cognitive Therapy Alone and in Combination with Antidepressants for Anxious Depression: A STAR*D Report

    Science.gov (United States)

    Farabaugh, Amy; Alpert, Jonathan; Wisniewski, Stephen R.; Otto, Michael W.; Fava, Maurizio; Baer, Lee; Perlis, Roy; Friedman, Edward S.; Nyer, Maren; Bitran, Stella; Balasubramani, G.K.; Inamori, Aya; Trivedi, Madhukar; Thase, Michael

    2012-01-01

    Background Anxious depression, defined as MDD with high levels of anxiety, has been associated with lower rates of antidepressant response and remission as well as greater chronicity, suicidality and antidepressant side-effect burden. The primary aim of this study was to assess the effectiveness of cognitive therapy (CT) alone or in combination with medications for anxious versus non-anxious depression. Methods We assessed the STAR*D study participants who were partial or non-responders to citalopram. Subjects were then either switched (n = 696) to a new antidepressant or to CT alone, or they were kept on citalopram and augmented (n = 577) with another antidepressant or CT. We compared response and remission rates of those who met criteria for anxious depression to those who did not across treatment conditions. Results Those with anxious depression had significantly lower remission rates based on the QIDS, whether assigned to switch or augmentation, compared to those with non-anxious depression. Those with anxious depression, compared to those without, had significantly lower response rates based on the QIDS only in the switch group. There was no significant interaction between anxious depression and treatment assignment. Limitations Limitations include the use of citalopram as the only Level 1 pharmacotherapy and medication augmentation option, depression-focused CT rather than anxiety-focused CT, and focus on acute treatment outcomes. Conclusions Individuals with anxious depression appear to experience higher risk of poorer outcome following pharmacotherapy and/or CT after an initial course of SSRI, and continued efforts to target this challenging form of depression are needed. PMID:22877961

  20. Electronic Effects of Aluminum Complexes in the Copolymerization of Propylene Oxide with Tricyclic Anhydrides: Access to Well-Defined, Functionalizable Aliphatic Polyesters.

    Science.gov (United States)

    Van Zee, Nathan J; Sanford, Maria J; Coates, Geoffrey W

    2016-03-02

    The synthesis of well-defined and functionalizable aliphatic polyesters remains a key challenge in the advancement of emerging drug delivery and self-assembly technologies. Herein, we investigate the factors that influence the rates of undesirable transesterification and epimerization side reactions at high conversion in the copolymerization of tricyclic anhydrides with excess propylene oxide using aluminum salen catalysts. The structure of the tricyclic anhydride, the molar ratio of the aluminum catalyst to the nucleophilic cocatalyst, and the Lewis acidity of the aluminum catalyst all influence the rates of these side reactions. Optimal catalytic activity and selectivity against these side reactions requires a careful balance of all these factors. Effective suppression of undesirable transesterification and epimerization was achieved even with sterically unhindered monomers using a fluorinated aluminum salph complex with a substoichiometric amount of a nucleophilic cocatalyst. This process can be used to synthesize well-defined block copolymers via a sequential addition strategy.

  1. Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review

    Science.gov (United States)

    Hamid, Hazrulrizawati A.; Ramli, Aizi N. M.; Yusoff, Mashitah M.

    2017-01-01

    Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John’s wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants. PMID:28293192

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

    Directory of Open Access Journals (Sweden)

    Shigeyuki Chaki

    2015-09-01

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

  3. Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.

    Science.gov (United States)

    Cox, Georgina R; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N; Parker, Alexandra G; Hetrick, Sarah E

    2014-11-30

    Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when

  4. Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands

    Science.gov (United States)

    Chilmonczyk, Zdzisław; Bojarski, Andrzej Jacek; Pilc, Andrzej; Sylte, Ingebrigt

    2015-01-01

    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. PMID:26262615

  5. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    Science.gov (United States)

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  6. Effect of diclofenac and antidepressants on the inflammatory response in astrocyte cell culture.

    Science.gov (United States)

    Al-Amin, Md Mamun; Uddin, Mir Muhammad Nasir; Rahman, Md Mahbubur; Reza, Hasan Mahmud; Rana, Md Sohel

    2013-12-01

    Central nervous system (CNS) has a completely separate immune system that communicates with the neurons by small molecules called cytokines. Cytokines are involved in many crucial processes in neuron including cell metabolism and neurotransmitter synthesis. It has been reported that cytokine imbalance is involved in the progression of many CNS diseases such as neuropsychiatric disorders (depression, schizophrenia, autism, and bipolar disorder) and neurodegenerative disorders (Parkinson's and Alzheimer's disease). Here, the effects of diclofenac, different antidepressants (sertraline, venlafaxine, and fluvoxamine), and vitamin B₆ (pyridoxine) on IL-10 and tumor necrosis factor-α (TNF-α) change with and without immune challenges with lipopolysaccharide (LPS) were investigated in in vitro culture of astrocytes from 2-day-old Swiss-Albino mice. Diclofenac and Sertraline significantly (p 0.05) TNF-α in the astrocyte culture. Antidepressant (sertraline) showed positive effects (increased IL-10 and reduced TNF-α level) possibly through the suppression of Th1 lymphocytes and monocytes and stimulation of Th2 lymphocytes and monocytes/macrophages. NSAID (diclofenac) showed positive immune regulation effect possibly through the inhibition of cyclo-oxygenase enzyme. Based on these findings, it may conclude that, diclofenac and antidepressants (sertraline) may positively contribute in the cytokine production in astrocyte cell culture.

  7. Diagnostic conversion to bipolar disorder in unipolar depressed patients participating in trials on antidepressants.

    Science.gov (United States)

    Holmskov, J; Licht, R W; Andersen, K; Bjerregaard Stage, T; Mørkeberg Nilsson, F; Bjerregaard Stage, K; Valentin, J B; Bech, P; Ernst Nielsen, R

    2017-02-01

    In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder. A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD=11.9) participating in three randomized trials on antidepressants conducted in the period 1985-1994. The independent effects of explanatory variables were examined by applying Cox regression analyses. The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10-1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found. The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome. In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion. Copyright © 2016. Published by Elsevier Masson SAS.

  8. Combining Organocatalysis and Lanthanide Catalysis: A Sequential One-Pot Quadruple Reaction Sequence/Hetero-Diels-Alder Asymmetric Synthesis of Functionalized Tricycles.

    Science.gov (United States)

    Dochain, Simon; Vetica, Fabrizio; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-12-23

    A stereoselective one-pot synthesis of functionalized complex tricyclic polyethers has been achieved using the combination of secondary amine and lanthanide catalysis. This one-pot quadruple reaction/Hetero-Diels-Alder sequence gave good yields (per step) as well as excellent diastereo- and enantioselectivities. Furthermore, the particular combination of lanthanide complexes with organocatalysis is one of the first examples described for sequential catalysis. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis of enantioenriched γ-quaternary cycloheptenones using a combined allylic alkylation/Stork–Danheiser approach: preparation of mono-, bi-, and tricyclic systems

    KAUST Repository

    Bennett, Nathan B.

    2012-01-01

    A general method for the synthesis of β-substituted and unsubstituted cycloheptenones bearing enantioenriched all-carbon γ-quaternary stereocenters is reported. Hydride or organometallic addition to a seven-membered ring vinylogous ester followed by finely tuned quenching parameters achieves elimination to the corresponding cycloheptenone. The resulting enones are elaborated to bi- and tricyclic compounds with potential for the preparation of non-natural analogs and whose structures are embedded in a number of cycloheptanoid natural products.

  10. A Synthesis of the Tricyclic Core Structure of FR901483 Featuring an Ugi Four-Component Coupling and a Remarkably Selective Elimination Reaction1

    Science.gov (United States)

    Seike, Hirofumi

    2011-01-01

    Three key reactions, an efficient Ugi four-component coupling, a regiospecific, base-mediated elimination reaction, and an intramolecular nitrone/alkene [3+2] cycloaddition, were used to achieve an effective synthesis of the tricyclic molecular framework of the immunosuppressant FR901483. The outcome of a control experiment supports the idea that an internal deprotonation by an alkoxide ion is the origin of the site selectivity observed in the base-induced elimination of hydroxy mesylate 17. PMID:22114366

  11. A Synthesis of the Tricyclic Core Structure of FR901483 Featuring an Ugi Four-Component Coupling and a Remarkably Selective Elimination Reaction.

    Science.gov (United States)

    Seike, Hirofumi; Sorensen, Erik J

    2008-03-18

    Three key reactions, an efficient Ugi four-component coupling, a regiospecific, base-mediated elimination reaction, and an intramolecular nitrone/alkene [3+2] cycloaddition, were used to achieve an effective synthesis of the tricyclic molecular framework of the immunosuppressant FR901483. The outcome of a control experiment supports the idea that an internal deprotonation by an alkoxide ion is the origin of the site selectivity observed in the base-induced elimination of hydroxy mesylate 17.

  12. Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos Treatment-resistant depression: review of pharmacologic antidepressant strategies

    Directory of Open Access Journals (Sweden)

    Milena Antunes Santos

    2006-01-01

    , LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. RESULTS: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60% of those with thyroid hormone and tricyclics, 0% of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI, 50% of those with pindolol, 100% of those with carbamazepine and 40% of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measures. CONCLUSION: Only lithium and thyroid hormone showed efficacy as antidepressant augmentation strategies for TRD. Olanzapine was reasonably studied and did not prove its efficacy. There were just a few studies on buspirone and pindolol and they were not favorable to them. Carbamazepine was studied very little. Lamotrigine was not adequately evaluated.

  13. Antidepressant prescribing in community cancer care.

    Science.gov (United States)

    Ashbury, Fredrick D; Madlensky, Lisa; Raich, Peter; Thompson, Mark; Whitney, Geoff; Hotz, Ken; Kralj, Boris; Edell, William S

    2003-05-01

    To describe patterns of antidepressant (ADs) prescribing in community oncology practice. Data were collected using an electronic medical record on all staged breast, colon, and lung cancer patients in three community-based oncology practices. The data were analyzed retrospectively, using descriptive and bivariate analyses and multivariate logistic regression modeling. There were 850 breast, 299 colon, and 473 lung cancer patients identified in this analysis. Overall, 19.2% of breast, 11% of colon, and 13.7% of lung cancer patients had been prescribed ADs during the 2-year period. The clinic in which cancer treatment was received predicted AD prescribing. The relationship between AD administration and age proved to be nonlinear; the pattern exhibited an "inverted U" shape. Patients with comorbidities and on pain medications were more likely to be administered ADs. Colon cancer patients on pain medications were five times more likely to be administered ADs than those not on pain medications. While some predictors of AD prescribing appear to be consistent with other studies, such as being on pain medication, there is still a great amount of variability in prescribing patterns across community practices, age groups, and cancer diagnoses. This study demonstrates that prescriptions of ADs seem to be influenced by parameters other than psychopathology. Given the importance of major depression in oncology care, diagnosis of psychiatric disorders and prescription patterns of psychotropics should be part of the routine monitoring and quality management in oncology patient care.

  14. A new strategy for antidepressant prescription

    Directory of Open Access Journals (Sweden)

    Francis Lavergne

    2010-11-01

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

  15. The acetylenic tricyclic bis(cyano enone), TBE-31, targets microtubule dynamics and cell polarity in migrating cells.

    Science.gov (United States)

    Chan, Eddie; Saito, Akira; Honda, Tadashi; Di Guglielmo, Gianni M

    2016-04-01

    Cell migration is dependent on the microtubule network for structural support as well as for the proper delivery and positioning of polarity proteins at the leading edge of migrating cells. Identification of drugs that target cytoskeletal-dependent cell migration and protein transport in polarized migrating cells is important in understanding the cell biology of normal and tumor cells and can lead to new therapeutic targets in disease processes. Here, we show that the tricyclic compound TBE-31 directly binds to tubulin and interferes with microtubule dynamics, as assessed by end binding 1 (EB1) live cell imaging. Interestingly, this interference is independent of in vitro tubulin polymerization. Using immunofluorescence microscopy, we also observed that TBE-31 interferes with the polarity of migratory cells. The polarity proteins Rac1, IQGAP and Tiam1 were localized at the leading edge of DMSO-treated migrating cell, but were observed to be in multiple protrusions around the cell periphery of TBE-31-treated cells. Finally, we observed that TBE-31 inhibits the migration of Rat2 fibroblasts with an IC50 of 0.75 μM. Taken together, our results suggest that the inhibition of cell migration by TBE-31 may result from the improper maintenance of cell polarity of migrating cells.

  16. Synthesis and evaluation of tricyclic dipyrido diazepinone derivatives as inhibitors of secretory phospholipase A2 with anti-inflammatory activity.

    Science.gov (United States)

    Thimmegowda, N R; Dharmappa, K K; Kumar, C S Ananda; Sadashiva, M P; Sathish, A D; Nanda, B L; Vishwanath, B S; Rangappa, K S

    2007-01-01

    A series of tricyclic dipyrido diazepinone derivatives 6(a-f) bearing different substituents at the tenth position of diazepinone ring were designed and are characterized by 1H NMR, FTIR and X-Ray crystallography studies. The synthesised derivatives are tested in-vitro phospholipase A2 (PLA2) enzyme inhibitory activity and in-vivo anti-inflammatory activity against purified group I and group II PLA2 enzymes from the snake venom and human pleural fluid. Compounds bearing aromatic ring with different substituents at different positions shown varied specificity. The 6f derivative with strong electron withdrawing nitro (-NO2) and trifluoromethyl (-CF3) groups at ortho and para positions respectively shown greater inhibitory activity. Inhibitory effect of the compound appeared to be direct interaction with active site and likely competes with substrates as supported by substrate dependent and calcium independent assays. The IC50 value of potent PLA2 inhibitor 6f was 22.1 microM and showed similar potency in the neutralization of in vivo PLA2 induced mouse paw edema and hemolytic activity.

  17. Spectroscopic and structural investigation on intermediates species structurally associated to the tricyclic bisguanidine compound and to the toxic agent, saxitoxin

    Science.gov (United States)

    Romani, Davide; Tsuchiya, Shigeki; Yotsu-Yamashita, Mari; Brandán, Silvia Antonia

    2016-09-01

    In the present work, we have studied the structural, topological and spectroscopic properties of five cyclic and of open chain species derived from tricyclic bisguanidine compound in gas and aqueous phases combining the DFT calculations with the experimental infrared and 1H NMR, 13C NMR and UV-visible spectra. These species are members of the saxitoxin family and they were recently synthesized by Tsuchiya et al. (Chemistry. A European Journal, 21 (2015) 7835-7840). Here, the self consistent reaction force (SCRF) calculations were employed in aqueous medium to study the solvation energies by using the polarized continuum (PCM) and solvation (SM) models. All the calculations were performed with the 6-31G* and 6-311++G** basis sets. The atomic charges, electrostatic potentials, bond order, stabilization energy, topological properties suggest the structural connection between the cyclic cationic and saxitoxin species while the electrophilicity and nucleophilicity indexes could be one of the explanations for the Nav blocking activities of these species. The complete vibrational assignments for all the species are reported. The predicted spectra present a reasonable concordance with the corresponding experimental ones.

  18. Identification of the chemical constituents in aqueous extract of Zhi-Qiao and evaluation of its antidepressant effect.

    Science.gov (United States)

    Wu, Ming; Zhang, Hongwu; Zhou, Chao; Jia, Hongmei; Ma, Zhuo; Zou, Zhongmei

    2015-04-16

    The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ) has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents of ZQ aqueous extract or its anti-depression effects. Firstly, this research reported the on-line identification of the chemical constituents in the aqueous extract of ZQ by coupling ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 31 chemical constituents were identified in ZQ aqueous extract, including one tannic acid, five flavones, 13 flavanones, one limonoid, three coumarins, three cyclic peptides, and five polymethoxylated flavonoids. The antidepressant effect of ZQ aqueous extract was evaluated in vivo and the results indicated that the mice immobility time during the forced swimming test and the tail suspension test were significantly reduced with ZQ treatment. MTT assays showed both ZQ aqueous extract and its major constituents (naringin, hesperidin, neohesperidin, and nobiletin) had neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells. The in vivo and in vitro results suggest that ZQ has an antidepressant effect.

  19. Identification of the Chemical Constituents in Aqueous Extract of Zhi-Qiao and Evaluation of Its Antidepressant Effect

    Directory of Open Access Journals (Sweden)

    Ming Wu

    2015-04-01

    Full Text Available The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents of ZQ aqueous extract or its anti-depression effects. Firstly, this research reported the on-line identification of the chemical constituents in the aqueous extract of ZQ by coupling ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF/MS. A total of 31 chemical constituents were identified in ZQ aqueous extract, including one tannic acid, five flavones, 13 flavanones, one limonoid, three coumarins, three cyclic peptides, and five polymethoxylated flavonoids. The antidepressant effect of ZQ aqueous extract was evaluated in vivo and the results indicated that the mice immobility time during the forced swimming test and the tail suspension test were significantly reduced with ZQ treatment. MTT assays showed both ZQ aqueous extract and its major constituents (naringin, hesperidin, neohesperidin, and nobiletin had neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells. The in vivo and in vitro results suggest that ZQ has an antidepressant effect.

  20. Treatment Resistant Depression with Loss of Antidepressant Response: Rapid—Acting Antidepressant Action of Dextromethorphan, A Possible Treatment Bridging Molecule

    Science.gov (United States)

    Lauterbach, Edward C.

    2016-01-01

    Dextromethorphan (DM) may have ketamine—like rapid—acting, treatment—resistant, and conventional antidepressant effects.1,2 This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment—resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid—acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days. Upon full relapse in DSM-5 MDD while taking 600 mg/day of the strong CYP2D6 inhibitor bupropion XL, a 300 mg oral loading dose of DM was given, followed by 60 mg po bid after an additional dose—finding period, without side effects. DM exhibited a ketamine—like rapid—acting antidepressant effect, thought to be mediated by mTOR activation (related to NMDA PCP site antagonism, sigma-1 and beta adrenergic receptor stimulation) and 5HTT inhibition, resulting in AMPA receptor trafficking, and dendritogenesis, spinogenesis, synaptogenesis, and increased neuronal survival (related to NMDA antagonism and sigma-1 and mTOR signaling). This report appears to be the first report of a rapid—acting effect in unipolar MDD and adds to antidepressant effects observed in the retrospective chart review of 77 patients with Bipolar II Disorder (Kelly and Lieberman 2014). If replicated, there is some reason to think that the administration of other agents with DM, such as lithium or D-cycloserine, might prolong the duration of the rapid-antidepressant effect. PMID:27738380

  1. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

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

  2. Impact of Antidepressant Drugs on Sexual Function and Satisfaction.

    Science.gov (United States)

    Baldwin, David S; Manson, Chris; Nowak, Magda

    2015-11-01

    Pleasurable sexual activity is important in many human relationships and can provide a sense of physical, emotional and social well-being. Depressive symptoms and depressive illness are associated with impairments in sexual function and sexual dissatisfaction in untreated and treated patients. Most currently available antidepressant drugs are associated with development or worsening of sexual dysfunction in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts, but can persist over long periods, reducing self-esteem and affecting mood and relationships adversely. Sexual difficulties during antidepressant treatment typically have many possible causes but the incidence and nature of dysfunction varies between drugs. Many interventions can be considered when managing sexual dysfunction associated with antidepressants but no approach is 'ideal'. Because treatment-emergent sexual difficulties are less frequent with certain drugs, presumably related to differences in pharmacological properties, and since current interventions are suboptimal, a lower incidence of sexual dysfunction is a relevant tolerability target when developing novel antidepressants.

  3. Is there a placebo problem in antidepressant trials?

    Science.gov (United States)

    Yang, Huaiyu; Cusin, Cristina; Fava, Maurizio

    2005-01-01

    In psychiatry, particularly in antidepressant clinical studies, placebo-controlled trials often yield results that are very difficult to interpret because of robust placebo responses. Meta-analyses of trials in major depressive disorder (MDD) suggest that drug-placebo differences in response rates range from 11% to 18%. However, in trials of marketed antidepressants present in the FDA databases, antidepressant drugs were superior to placebo in only 45 out of 93 RCTs (48%), and the placebo response overall appears to have increased over time. This gradual increase in placebo response rates may lead to delays in bringing new antidepressant treatments to the market, increased costs of antidepressant drug development and, in some cases, decisions to stop the development of certain compounds, or FDA decisions to not approve new treatments. A number of possible contributing factors to this significant placebo response in MDD have been identified, but further studies are needed. Many of the remedies used by researchers to minimize the placebo response, such as lead-in periods or shortening the duration of study visits, have failed to show consistent benefits. From our analysis of published studies, it appears that expectations about the speed of response may be shaped by the duration of the trial and that most of the placebo response occurs in the first half of the trial, regardless of its duration. These observations have led us to develop a novel approach to the placebo response problem called the Sequential Parallel Comparison Design.

  4. Peripheral administration of lactate produces antidepressant-like effects

    KAUST Repository

    Carrard, A

    2016-10-18

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

  5. Merobatzelladines A and B, Anti-Infective Tricyclic Guanidines from a Marine Sponge Monanchora sp.

    NARCIS (Netherlands)

    Takishima, S.; Ishiyama, A.; Iwatsuki, M.; Otoguro, K.; Yamada, H.; Omura, S.; Kobayashi, H.; van Soest, R.W.M.; Matsunaga, S.

    2009-01-01

    Merobatzelladines A (1) and B (2) have been isolated from a marine sponge Monanchora sp. as antibacterial constituents. Their structures including relative stereochemistry were determined by interpretation of spectral data. The absolute stereochemistry of merobatzelladine B (2) was elucidated after

  6. Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon [College of Medicine, Univ. of Korea, Seoul (Korea, Republic of)

    2003-07-01

    Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. 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.

  7. Antidepressant prescriptions in first and second generation ethnic minorities in Dutch general practice.

    NARCIS (Netherlands)

    Dijk, L. van; Volkers, A.C.; Verheij, R.A.

    2007-01-01

    Background: Ethnic minorities have poor access and different pathways to mental health care as compared to indigenous populations, but less is known about differences in antidepressant treatment in depressed patients among ethnic minorities. This papers studies antidepressant treatment in depressed

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  9. Evaluation of antidepressant effect of ethanolic extract of Rosa damascena using forced swimming test

    Directory of Open Access Journals (Sweden)

    Karim Dolati

    2011-12-01

    Conclusion: Although ethanolic extract did not have antidepressant effect, we cannot rule out this effect altogether. In our opinion, antidepressant effect is masked by CNS depression effect of ethanolic extract of R. damascena.

  10. Patient and GP characteristics associated with antidepressant treatment in depressed patients: a multilevel analysis.

    NARCIS (Netherlands)

    Dijk, L. van; Volkers, A.; Bakker, D. de

    2007-01-01

    Background: Antidepressants are frequently prescribed drugs in Dutch general practice, but patients differ in the treatment they receive. Both patient and GP characteristics may explain this difference. Objectives: To identify patient and GP characteristics associated with antidepressant treatment i

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

    Directory of Open Access Journals (Sweden)

    Ashok K. Sharma

    2015-02-01

    Conclusions: Nifedipine, fluvoxamine, venlafaxine and tianeptine possess antidepressant activity and nifedipine exhibits synergistic antidepressant activity with fluvoxamine, venlafaxine and tianeptine. [Int J Basic Clin Pharmacol 2015; 4(1.000: 82-88

  12. 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.

  13. 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.

  14. Antidepressant-associated sexual dysfunction: impact, effects, and treatment.

    Science.gov (United States)

    Higgins, Agnes; Nash, Michael; Lynch, Aileen M

    2010-01-01

    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 delayed orgasm, to erection or delayed ejaculation problems. There are a number of case reports of sexual side effects, such as priapism, painful ejaculation, penile anesthesia, loss of sensation in the vagina and nipples, persistent genital arousal and nonpuerperal lactation in women. The focus of this article is to explore the incidence, pathophysiology, and treatment of antidepressant iatrogenic sexual dysfunction.

  15. Evaluations of antidepressant activity of Anacyclus pyrethrum root extract

    Directory of Open Access Journals (Sweden)

    Badhe S

    2010-01-01

    Full Text Available The present study was designed to screen antidepressant activity of Anacyclus pyrethrum (AP root extract. An experiment was designed by different method such as Locomotor activity, Haloperidol-induced catalepsy, Forced swim test (FST, Tail suspension test (TST, Clonidine-induced hypothermia and Reserpine-induced hypothermia on Swiss male albino mice. Standard root extract of Anacyclus pyrethrum (AP root extract showed an increase in ambulatory behaviour indicating a stimulant effect of the photoactometer. AP root extract produces a significant antidepressant effect in both FST and TST as they reduced the immobility. AP root extract was found to be effective in reversing hypothermia produced by clonidine and reserpine. In our study, we found that AP root extract inhibited haloperidol-induced catalepsy. These study suggest that AP root extract might produce antidepressant effect by interaction with adrenergic and dopamine receptor thereby increasing the level of noradrenaline and dopamine in brains of mice.

  16. Sudden cardiac death secondary to antidepressant and antipsychotic drugs.

    Science.gov (United States)

    Sicouri, Serge; Antzelevitch, Charles

    2008-03-01

    A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use.

  17. 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....

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

    Directory of Open Access Journals (Sweden)

    Miyasaka Lincoln Sakiara

    2003-01-01

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

  19. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.

    Science.gov (United States)

    Nibuya, M; Nestler, E J; Duman, R S

    1996-04-01

    The present study demonstrates that chronic, but not acute, adminstration of several different classes of antidepressants, including serotonin- and norepinephrine-selective reuptake inhibitors, increases the expression of cAMP response element binding protein (CREB) mRNA in rat hippocampus. In contrast, chronic administration of several nonantidepressant psychotropic drugs did not influence expression of CREB mRNA, demonstrating the pharmacological specificity of this effect. In situ hybridization analysis demonstrates that antidepressant administration increases expression of CREB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cell layers of the hippocampus. In addition, levels of CRE immunoreactivity and of CRE binding activity were increased by chronic antidepressant administration, which indicates that expression and function of CREB protein are increased along with its mRNA. Chronic administration of the phosphodiesterase (PDE) inhibitors rolipram or papaverine also increased expression of CREB mRNA in hippocampus, demonstrating a role for the cAMP cascade. Moreover, coadministration of rolipram with imipramine resulted in a more rapid induction of CREB than with either treatment alone. Increased expression and function of CREB suggest that specific target genes may be regulated by these treatments. We have found that levels of brain-derived neurotrophic factor (BDNF) and trkB mRNA are also increased by administration of antidepressants or PDE inhibitors. These findings indicate that upregulation of CREB is a common action of chronic antidepressant treatments that may lead to regulation of specific target genes, such as BDNF and trkB, and to the long-term effects of these treatments on brain function.

  20. Antidepressant treatment and cultural differences - a survey of the attitudes of physicians and patients in Sweden and Turkey

    Directory of Open Access Journals (Sweden)

    McConnachie Alex

    2010-11-01

    Full Text Available Abstract Background The presenting symptoms of depression can be influenced by cultural differences. This study was conducted to compare the presenting symptoms and response to antidepressant medication of patients in Sweden and Turkey, two culturally different European countries. Methods Recruitment was triggered when adult patients were diagnosed with a depressive or anxiety disorder by a primary care physician and prescribed an antidepressant. Physicians and patients recorded presenting symptoms and completed relevant questionnaires just before and 8 weeks after starting treatment with an antidepressant. These included the Hospital Anxiety and Depression Scale (HADS, the Clinical Global Impressions (CGI scale, the Sheehan Disability Scale (SDS, and Likert scales gauging the importance of physical and psychological symptoms. Patients also rated severity of prominent symptoms (depression, anxiety, stress, sleep and pain from zero to ten. The outcomes were compared between patients from Sweden and Turkey using Fisher's Exact test and two-sample t-tests. Results The study was conducted in 460 patients (107, 23.3% in Sweden; 353, 76.7% in Turkey. Presenting symptoms differed between Sweden and Turkey, with Turkish patients more likely to present with physical symptoms, and report a higher number of physical symptoms (mean 2.4 vs. 1.4, p Conclusions The presenting symptoms of patients diagnosed with a depressive or anxiety disorder by a primary care physician and prescribed an antidepressant differ between Turkey and Sweden. Patients in Turkey were more likely to present with physical symptoms than patients in Sweden and present with more physical symptoms. After 8 weeks of antidepressant treatment, the improvement from baseline was greater in Turkish patients, and this was reflected in their improved functioning.

  1. In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection.

    Science.gov (United States)

    Xu, Y F; Lian, D W; Chen, Y Q; Cai, Y F; Zheng, Y F; Fan, P L; Ren, W K; Fu, L J; Li, Y C; Xie, J H; Cao, H Y; Tan, B; Su, Z R; Huang, P

    2017-06-01

    This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 μg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 μg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1β, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development. Copyright © 2017 American Society for Microbiology.

  2. Drugs on the Internet, part II: antidepressant medication web sites.

    Science.gov (United States)

    Morgan, Melissa; Montagne, Michael

    2011-01-01

    Antidepressant medications have been the fastest growing category of use of pharmaceutical products over the past decade. Selected Internet web sites providing information on antidepressant medications were identified and assessed using code of conduct criteria for posting health information on the Internet as developed by the Health on the Internet Foundation. Thirteen representative web sites were evaluated. Degree of compliance with each of the eight criterion varied by site, though all 13 sites met the criterion for legality of content and conduct on their web site. WebMD and FamilyDoctor.org met most of the criteria, while pharmaceutical company sites tended to meet the fewest criteria.

  3. 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.

  4. CLINICAL EFFICACY OF CENTPORPAZINE-A NEW ANTIDEPRESSANT

    Science.gov (United States)

    Srivastava, J.S.; Gupta, P.P.; Asthana, O.P.; Nityanand, S.; Devi, S.; Doongaji, D.R.; Sethi, B.B.; Singh, Gurmeet; Srimal, R.C.; Dhawan, B.N.

    1992-01-01

    Efficacy of centpropazine, a new antidepressant, has been evaluated in forty two patients of endogenous depression. The 4 week open trial was carried out in a dose-range of 40 to 120mg per day. A significant lowering of Hamilton Depression Rating Scale (HDRS) score was observed in 34 patient. The antidepressant effect could be detected in 9 patients within one week, in 28 cases in two weeks and in all the 34 patients by third week. Giddiness, headache, dryness of mouth and weakness were reported by 11 patients. PMID:21776129

  5. Antidepressant activity of Simvastatin in behavioral models of depression in rats

    Directory of Open Access Journals (Sweden)

    Archit Patke

    2015-07-01

    Conclusions: Lowering cholesterol levels with statins not only reduces risks for cardiovascular events, but also affect serotonergic neurotransmission, leading to clinical efficacy of standard antidepressants. Simvastatin can augment the antidepressant effects of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans. [Int J Res Med Sci 2015; 3(7.000: 1666-1671

  6. What is the mechanism of Ketamine's rapid-onset antidepressant effect? A concise overview of the surprisingly large number of possibilities.

    Science.gov (United States)

    Strasburger, S E; Bhimani, P M; Kaabe, J H; Krysiak, J T; Nanchanatt, D L; Nguyen, T N; Pough, K A; Prince, T A; Ramsey, N S; Savsani, K H; Scandlen, L; Cavaretta, M J; Raffa, R B

    2017-04-01

    Abundant clinical data now confirm that ketamine produces a remarkable rapid-onset antidepressant effect - hours or days - in contrast to the delayed onset (typically weeks) of current antidepressant drugs. This surprising and revolutionary finding may lead to the development of life-saving pharmacotherapy for depressive illness by reducing the high suicide risk associated with the delayed onset of effect of current drugs. As ketamine has serious self-limiting drawbacks that restrict its widespread use for this purpose, a safer alternative is needed. Our objective is to review the proposed mechanism(s) of ketamine's rapid-onset antidepressant action for new insights into the physiological basis of depressive illness that may lead to new and novel targets for antidepressant drug discovery. A search was conducted on published literature (e.g. PubMed) and Internet sources to identify information relevant to ketamine's rapid-acting antidepressant action and, specifically, to the possible mechanism(s) of this action. Key search words included 'ketamine', 'antidepressant', 'mechanism of action', 'depression' and 'rapid acting', either individually or in combination. Information was sought that would include less well-known, as well as well-known, basic pharmacologic properties of ketamine and that identified and evaluated the several hypotheses about ketamine's mechanism of antidepressant action. Whether the mechanistic explanation for ketamine's rapid-onset antidepressant action is related to its well-known antagonism of the NMDA (N-Methyl-d-aspartate) subtype of glutamate receptor or to something else has not yet been fully elucidated. The evidence from pharmacologic, medicinal chemistry, animal model and drug-discovery sources reveals a wide variety of postulated mechanisms. The surprising discovery of ketamine's rapid-onset antidepressant effect is a game-changer for the understanding and treatment of depressive illness. There is some convergence on NMDA receptor

  7. High performance liquid chromatographic determination of ultra traces of two tricyclic antidepressant drugs imipramine and trimipramine in urine samples after their dispersive liquid-liquid microextraction coupled with response surface optimization.

    Science.gov (United States)

    Shamsipur, Mojtaba; Mirmohammadi, Mehrosadat

    2014-11-01

    Dispersive liquid-liquid microextraction (DLLME) coupled with high performance liquid chromatography by ultraviolet detection (HPLC-UV) as a fast and inexpensive technique was applied to the determination of imipramine and trimipramine in urine samples. Response surface methodology (RSM) was used for multivariate optimization of the effects of seven different parameters influencing the extraction efficiency of the proposed method. Under optimized experimental conditions, the enrichment factors and extraction recoveries were between 161.7-186.7 and 97-112%, respectively. The linear range and limit of detection for both analytes found to be 5-100ng mL(-1) and 0.6ng mL(-1), respectively. The relative standard deviations for 5ng mL(-1) of the drugs in urine samples were in the range of 5.1-6.1 (n=5). The developed method was successfully applied to real urine sample analyses.

  8. Effect of pharmacist intervention on improving antidepressant medication adherence and depression symptomology: A systematic review and meta-analysis.

    Science.gov (United States)

    Readdean, Kevin C; Heuer, Albert J; Scott Parrott, J

    2017-05-22

    Depression is a widespread disease with effective pharmacological treatments, but low medication adherence. Pharmacists play a key role in supporting medication adherence in patients with depression given their accessibility to patients. The aim of this review was to systematically evaluate the impact of pharmacist interventions on adherence to antidepressants and clinical symptomology among adult outpatients with depressive disorders. A systematic review of controlled trials (both randomized and non-randomized) was conducted. Studies were obtained through a search of PubMed, Academic Search Premier, and Cochrane Library databases. Studies which included a pharmacist intervention to improve medication adherence in outpatients age 17 and above with a depressive disorder diagnosis and antidepressant treatment were included. Twelve publications met inclusion criteria, representing a total of 15,087 subjects: 1379 (9%) intervention and 13,708 (91%) control. The interventions in each selected publication included some level of in-person counseling and education to promote antidepressant adherence. The pooled odds ratio for medication adherence at 6 months was 2.50 (95% CI 1.62 to 3.86). There were no significant differences noted in subgroup meta-analyses except study location (US, Middle East or Europe) and setting. Only one of the identified studies reported statistically significant impacts of the pharmacist intervention on patient depression symptoms. The findings suggest that pharmacist interventions can enhance patient adherence to antidepressant medication in adult outpatients. However, this review failed to demonstrate a positive effect of these interventions on clinical symptoms. Additional longitudinal research is recommended to investigate the multidimensional relationships between pharmacist interventions, patient adherence, and clinical outcomes. Pharmacists play a key role in supporting medication adherence in patients with depression given their

  9. 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…

  10. Effect of antidepressants on spatial memory deficit induced by dizocilpine.

    Science.gov (United States)

    Tao, Chenjuan; Yan, Weiwei; Li, Yuan; Lu, Xiaodong

    2016-10-30

    Cognitive deficits are a core symptom of schizophrenia. It is controversial whether antidepressants could improve cognitive symptoms in schizophrenia patients. The present study was designed to identify the therapeutic effect of antidepressants on cognitive deficits in schizophrenia. In the present study, adolescent rats were repeatedly exposed to dizocilpine, which can induce cognitive deficits associated with schizophrenia. Then these rats were treated by six antidepressants (fluvoxamine, sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine) or vehicle. The rats in the control group were exposed to vehicle during the study. Lastly, all rats' spatial memory (a major part of cognition) was assessed using the Morris water maze (MWM) test, and the density of hippocampal parvalbumin (PV) interneurons was evaluated to explore possible mechanisms underlying spatial memory change in schizophrenia. The results of the present study supported the hypothesis of a therapeutic effect of fluvoxamine and escitalopram on spatial memory deficit induced by dizocilpine. Additionally, the data of the present study suggested that fluvoxamine and escitalopram remitted hippocampal PV interneuron reduction induced by dizocilpine. The neuroprotective effect of fluvoxamine and escitalopram may partly explain the therapeutic effect of antidepressants on spatial memory deficit in schizophrenia patients.

  11. Continuation and maintenance use of antidepressants in recurrent depression

    NARCIS (Netherlands)

    Bockting, Claudi L H; ten Doesschate, Mascha C; Spijker, Jan; Spinhoven, Philip; Koeter, Maarten W J; Schene, Aart H

    2008-01-01

    Background: Maintenance antidepressant (AD) medication is the most commonly used preventive strategy in a highly recurrent disease, i. e. depression. Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice. The purpose was to exa

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

    African Journals Online (AJOL)

    Adele

    rates are found with spontaneous self-reporting and higher rates result when ... depression or anxiety is made or an antidepressant medication is likely to be ... It is obviously also important to assess pre-morbid and life- ... A person's subjective sense of sexual satisfaction is an important ..... American Psychiatric Association.

  13. Prevalence and patterns of antidepressant drug use during pregnancy

    NARCIS (Netherlands)

    Ververs, Tessa; Kaasenbrood, Hans; Visser, Gerard; Schobben, Fred; de Jong-van den Berg, Lolkje T. W.; Egberts, Toine

    2006-01-01

    Objective The aim of this study was to determine the extent and patterns of antidepressant use before, during and after pregnancy in a large population in The Netherlands. Methods Health care records and prescription data from one of the largest Dutch health insurance companies were analysed. The st

  14. 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,

  15. Antidepressant exposure during early pregnancy and congenital malformations

    DEFF Research Database (Denmark)

    Pedersen, Lars Henning

    are reassuring, however, an association with heart malformations has been suggested for e.g. paroxetine. A potential biological explanation will be reviewed. The potential teratogenic potential of antidepressants needs to be balanced against the obvious problems associated with under-treated maternal depression...

  16. Antidepressant use during pregnancy and asthma in the offspring

    DEFF Research Database (Denmark)

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

    2015-01-01

    in the offspring. METHODS: A cohort study was performed among all live singletons born in Denmark between 1996 and 2007. Mothers who had a diagnosis of depressive disorder and/or who used antidepressants 1 year before or during the index pregnancy were identified. Using a Cox proportional hazards regression model...

  17. Dopaminergic mechanism of antidepressant action in depressed patients.

    Science.gov (United States)

    Willner, Paul; Hale, Anthony S; Argyropoulos, Spilios

    2005-05-01

    Clinical studies have not yet determined a common mechanism of action for antidepressant drugs, which have primary sites of action on a variety of different neurotransmitter systems. However, a large body of evidence from animal studies demonstrates that sensitisation of D2-like dopamine receptors in the mesolimbic dopamine system may represent a 'final common pathway' in antidepressant action. The present study aimed to determine whether, consistent with data from animal studies, the clinical antidepressant action of selective serotonin reuptake inhibitors (SSRIs) is reversed by acute administration of a receptor antagonist selective for D2-like receptors in the mesolimbic dopamine system. The participants were patients diagnosed with major depressive disorder (n = 8) who had been treated successfully (Hamilton Depression Scale depressed, untreated volunteers (n = 10). They attended a psychiatric research ward on an out-patient basis, and received double-blind acute administration of either placebo, or a low dose of the selective dopamine D2/D3 receptor antagonist sulpiride (200 mg), in a counterbalanced order. Mood and psychomotor effects were assessed using visual analogue scales and the Fawcett-Clark Pleasure Capacity Scale. Sulpiride slightly improved subjective well-being in the control group, but in the antidepressant-treated patients, sulpiride caused a substantial reinstatement of depressed mood. These data are consistent with the hypothesis that sensitisation of D2-like receptors may be central to the clinical action of SSRIs.

  18. Antidepressants: Get Tips to Cope with Side Effects

    Science.gov (United States)

    ... because you have a better appetite when your depression symptoms ease up. Some antidepressants are more likely to cause ... bedtime if your doctor approves. Agitation, restlessness or anxiety can result ... Get regular exercise, such as jogging, biking or aerobics, or some ...

  19. Regio- and chemoselective N-1 acylation of indoles: Pd-catalyzed domino cyclization to afford 1,2-fused tricyclic indole scaffolds.

    Science.gov (United States)

    Liu, Yongxian; Huang, Yuanqiong; Song, Hongjian; Liu, Yuxiu; Wang, Qingmin

    2015-03-27

    A concise method for the synthesis of 1,2-fused tricyclic indole scaffolds by domino cyclization involving a Pd-catalyzed Sonogashira coupling, indole cyclization, regio- and chemoselective N-1 acylation, and 1,4-Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2-a]indole and hexahydro[1,5]diazocino[1,2-a]indole scaffolds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Stereoselective Construction of Spiro-Fused Tricyclic Frameworks by Sequential Reaction of Enynes, Imines, and Diazoalkenes with Rh(I) and Rh(II) Catalysts.

    Science.gov (United States)

    Hato, Yoshio; Oonishi, Yoshihiro; Yamamoto, Yasunori; Nakajima, Kiyohiko; Sato, Yoshihiro

    2016-09-02

    Stereoselective construction of spiro-fused tricyclic compounds from enynes having a tethered imine with diazoalkenes was achieved by Rh(I)- and Rh(II)-catalyzed sequential reactions. This method consists of three reactions, i.e., Rh(I)-catalyzed cyclization of enynes with a tethered imine, Rh(II)-catalyzed cyclopropanation with diazoalkenes, and Cope rearrangement. Notably, the sequential reactions can be operated in one pot, in which Rh(I) and Rh(II) catalysts work in relay without any serious catalyst deactivation to afford the spirocycles in a stereoselective manner.

  1. 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

  2. Neuroplasticity and major depression, the role of modern antidepressant drugs.

    Science.gov (United States)

    Serafini, Gianluca

    2012-06-22

    The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to provide a critical overview about neuroplasticity, depression and antidepressant drugs, a detailed Pubmed/Medline, Scopus, PsycLit, and PsycInfo search to identify all papers and book chapters during the period between 1980 and 2011 was performed. Pathological stress and depression determine relevant brain changes such as loss of dendritic spines and synapses, dendritic atrophy as well as reduction of glial cells (both in number and size) in specific areas such as the hippocampus and prefrontal cortex. An increased dendritic arborisation and synaptogenesis may instead be observed in the amygdala as a consequence of depression and stress-related disorders. While hippocampal and prefrontal functioning was impaired, amygdala functioning was abnormally amplified. Most of molecular abnormalities and biological changes of aberrant neuroplasticity may be explained by the action of glutamate. Antidepressant treatment is associated with neurogenesis, gliogenesis, dendritic arborisation, new synapse formation and cell survival both in the hippocampus and prefrontal cortex. Antidepressants (ADs) induce neuroplasticity mechanisms reversing the pathological effects of depression and stress-related disorders. The neuroplasticity hypothesis may explain the therapeutic and prophylactic action of ADs representing a new innovative approach to the pathophysiology of depression and stress-related disorders.

  3. EVALUATION OF ANTIDEPRESSANT ACTIVITY OF ALOCASIA MACRORRHIZOS ON MICE

    Directory of Open Access Journals (Sweden)

    Kateel Ramya

    2013-06-01

    Full Text Available The increased prevalence of depression at 12.3% rate and side effect profile of the existing antidepressants led to the present study which was designed to establish the role of natural herbal medicine Alocasia macrorrhizos as an antidepressant and to extend these results before the safe application in humans. 48 Albino male mice were divided into 2 sets each consisting of 4 groups with 6 animals in each group. Group1and 2 served as control and standard where as group3 and 4 were treated with hydroalcoholic extract of Alocasia macrorrhizos at the dose of 250mg/kg and 500mg/kg respectively. Drugs were suspended in 1% gumacasia and administered to mice orally one hour before test procedure. Forced swim test and tail suspension tests were standard animal models used for assessing antidepressant activity by recording the immobility time. Results from the study showed that hydroalcoholic extract of Alocasia macrorrhizos had significantly reduced immobility duration at the dose of 250mg/kg and 500mg/kg where it has shown better result than control group when subjected to the test procedures. Significant difference in immobility duration were noticed when these groups were compared to standard imipramine and there was a definite antidepressant effect observed with AM 500mg/kg whereas AM 250mg/kg values were comparable to imipramine. Hence we have concluded from the results of the study that hydroalcoholic extract of leaves of Alocasia macrorrhizos has the definite antidepressant effect which is comparable to Imipramine at 250mg/kg dose.

  4. Efficacy and Tolerability of Antidepressants in Pediatric Anxiety Disorders: a Systematic Review and Meta-Analysis

    Science.gov (United States)

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

    2015-01-01

    Background Randomized, controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety or tolerability of these medications in pediatric anxiety disorders. With this in mind, we sought to systematically review and conduct a meta-analysis of double-blind, placebo-controlled-trials of antidepressants in these conditions. Methods A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-OCD anxiety disorders was undertaken using a search of PubMed/Medline (1966–2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality and adverse events. Additionally, a series of pharmacologic variables (e.g., serotonin binding) were explored with regard to effect size. Results Data were included from 9 trials involving 1,673 patients and 6 medications, including 5 SSRIs and 3 SSNRI trials. All SSRI/SSNRIs evaluated demonstrated significant efficacy, and the meta-analytic summary estimate was of moderate magnitude (Cohen's d=0.64, confidence interval [CI]: 0.34–0.96, p=0.0017) and there was evidence of modest heterogenity (I2=0.26, p=0.107). Activation trended towards being more likely with antidepressant treatment (OR: 1.86, CI: 0.98–3.53, p=.054), but no increased risk was observed for nausea/abdominal symptoms (p=0.262) or discontinuation as a result of an adverse event (p=0.132). Treatment-emergent suicidality did not differ between antidepressant-treated youth and those who received placebo (OR: 1.3, CI: 0.53–3.2, p=0.514). Conclusions Data for 9 SSRI/SSNRIs suggest superiority to placebo for the treatment of pediatric anxiety disorders with a moderate effect size

  5. Molecular modeling studies of [6,6,5] Tricyclic Fused Oxazolidinones as FXa inhibitors using 3D-QSAR, Topomer CoMFA, molecular docking and molecular dynamics simulations.

    Science.gov (United States)

    Xu, Cheng; Ren, Yujie

    2015-10-15

    Coagulation factor Xa (Factor Xa, FXa) is a particularly promising target for novel anticoagulant therapy. The first oral factor Xa inhibitor has been approved in the EU and Canada in 2008. In this work, 38 [6,6,5] Tricyclic Fused Oxazolidinones were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics and Topomer CoMFA (comparative molecular field analysis) were used to build 3D-QSAR models. The results show that the best CoMFA model has q(2)=0.511 and r(2)=0.984, the best CoMSIA (comparative molecular similarity indices analysis) model has q(2)=0.700 and r(2)=0.993 and the Topomer CoMFA analysis has q(2)=0.377 and r(2)=0.886. The results indicated the steric, hydrophobic, H-acceptor and electrostatic fields play key roles in models. Molecular docking and molecular dynamics explored the binding relationship of the ligand and the receptor protein.

  6. Sociodemographic and clinical predictors of compliance with antidepressants for depressive disorders: systematic review of observational studies

    Directory of Open Access Journals (Sweden)

    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

  7. 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.

  8. Living alone and antidepressant medication use: a prospective study in a working-age population

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    Pulkki-Råback Laura

    2012-03-01

    Full Text Available Abstract Background An increasing proportion of the population lives in one-person households. The authors examined whether living alone predicts the use of antidepressant medication and whether socioeconomic, psychosocial, or behavioral factors explain this association. Methods The participants were a nationally representative sample of working-age Finns from the Health 2000 Study, totaling 1695 men and 1776 women with a mean age of 44.6 years. In the baseline survey in 2000, living arrangements (living alone vs. not and potential explanatory factors, including psychosocial factors (social support, work climate, hostility, sociodemographic factors (occupational grade, education, income, unemployment, urbanicity, rental living, housing conditions, and health behaviors (smoking, alcohol use, physical activity, obesity, were measured. Antidepressant medication use was followed up from 2000 to 2008 through linkage to national prescription registers. Results Participants living alone had a 1.81-fold (CI = 1.46-2.23 higher purchase rate of antidepressants during the follow-up period than those who did not live alone. Adjustment for sociodemographic factors attenuated this association by 21% (adjusted OR = 1.64, CI = 1.32-2.05. The corresponding attenuation was 12% after adjustment for psychosocial factors (adjusted OR = 1.71, CI = 1.38-2.11 and 9% after adjustment for health behaviors (adjusted OR = 1.74, CI = 1.41-2.14. Gender-stratified analyses showed that in women the greatest attenuation was related to sociodemographic factors and in men to psychosocial factors. Conclusions These data suggest that people living alone may be at increased risk of developing mental health problems. The public health value is in recognizing that people who live alone are more likely to have material and psychosocial problems that may contribute to excess mental health problems in this population group.

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

    Science.gov (United States)

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

    2015-03-01

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

  10. Differences in medication adherence and healthcare resource utilization patterns: older versus newer antidepressant agents in patients with depression and/or anxiety disorders.

    Science.gov (United States)

    Sheehan, David V; Keene, Matthew S; Eaddy, Michael; Krulewicz, Stan; Kraus, John E; Carpenter, David J

    2008-01-01

    depression, 31% had an anxiety disorder diagnosis and 6% had diagnoses for both an anxiety disorder and depression. Therapy change: Therapy change within 6 months occurred in 18% of patients receiving third-generation agents compared with 21% and 40% for second- and first-generation agents, respectively. The odds of a therapy change were significantly lower with third-generation antidepressants compared with both older agent cohorts. Adherence: Of patients receiving third-generation antidepressants, 33.6% were adherent compared with 29.3% and 12.4% of patients receiving second- and first-generation antidepressants, respectively. Newer agents also had better adherence rates across all diagnostic cohorts. After adjusting for baseline differences, the odds of being adherent to therapy were significantly lower for those taking second- and first-generation agents versus newer antidepressants. Among the newer agents, the proportion of patients adherent to their therapy was: venlafaxine extended release 38%, paroxetine controlled release (CR) 35%, escitalopram 34%, duloxetine 32% and bupropion extended release (XL) 31%. Healthcare utilization: Of the patients taking older antidepressants, 13% (second generation) and 21% (first generation) were hospitalized at least once for any reason compared with 12% of patients taking newer agents. Overall, the odds of all-cause hospitalization within 6 months of therapy initiation were significantly higher for patients taking older antidepressants. Among the newer agents, hospitalization rates ranged from 15.9% for duloxetine to 12.5% for paroxetine CR and bupropion XL. The unadjusted 6-month total medical costs (not including pharmacy costs) per patient were $US 3514 for second-generation, $US 5744 for first-generation and $US 3284 for newer antidepressants. After controlling for baseline differences, patients receiving second- and first-generation antidepressants incurred 12% and 44% higher costs, respectively. The unadjusted 6-month medical

  11. Antidepression medication improves quality of life in elderly patients with benign prostatic hyperplasia and depression.

    Science.gov (United States)

    Ma, Lina; Zhao, Xiaoling; Liu, Huizhen; Zhu, Hong; Yang, Wei; Qian, Yuying; Wang, Jieyu; Feng, Ming; Li, Yun

    2015-01-01

    We aim to explore the influence of an antidepression medication on symptom scores and quality of life in elderly patients with benign prostatic hyperplasia accompanied by depression. We conducted a randomized controlled clinical trial which included 94 elderly patients with benign prostatic hyperplasia accompanied by depression in Xuan Wu Hospital and Beijing Boai Hospital during August 2008 to May 2012. The study was designed to compare outcomes related to patient quality of life (QoL). The patients were randomly assigned to one of two groups, consisting of a control group (n = 47) and a therapy group (n = 47), and were followed up for 3 months. The pre-treatment and post-treatment changes among patients in the two groups were compared using their respective IPSS symptom scores, HAM-D scores, and scores on the Short Form 36 Health Survey. Following treatment, the patient IPSS symptom scores in the therapy group were significantly lower than those in the control group (10.74 ± 4.72 vs. 16.42 ± 8.09, respectively; t = 4.157, P benign prostatic hyperplasia accompanied by depression. Our findings suggest that an antidepression medication should be included when treating elderly patients with benign prostatic hyperplasia.

  12. Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine.

    Science.gov (United States)

    Kaur, Ginpreet; Invally, Mihir; Sanzagiri, Resham; Buttar, Harpal S

    2015-01-01

    The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of

  13. Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine

    Directory of Open Access Journals (Sweden)

    Ginpreet Kaur

    2015-01-01

    Full Text Available Background: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO (drumstick has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. Objective: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Materials and Methods: Alcoholic extracts of MO (MOE leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST, tail suspension test (TST, and locomotor activity test (LAT. Results: Significant changes in all tested activities (FST, TST, LAT of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the

  14. Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake.

    Science.gov (United States)

    Viljoen, Margaretha; Swanepoel, Annie; Bipath, Priyesh

    2015-03-01

    The term niacin is the generic name for the two compounds nicotinic acid and nicotinamide, the major dietary precursors for two important coenzymes, nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP. Niacin is important for the maintenance of cellular integrity and energy production and is involved in more than 500 intracellular reactions. Deficiencies of niacin may contribute to neuropsychiatric and neurodegenerative disorders. Patients who develop nutritional deficiencies as a result of poor dietary intake, especially inadequate intake of proteins and vitamins, could potentially suffer from niacin deficiency and NAD depletion. However, de novo synthesis of niacin and NAD in the kynurenine pathway of tryptophan metabolism may compensate for impaired dietary intake. The rate of synthesis of NAD and niacin from tryptophan oxidation depends on the induction of the enzyme indoleamine 2,3-dioxygenase (IDO) by pro-inflammatory cytokines such as interferon-gamma. Niacin synthesis is not limited by a decrease in tryptophan and excessive IDO activity may therefore lead to a decline in tryptophan levels. Antidepressants have an anti-inflammatory effect, including reduction of interferon-gamma and therefore inhibition of IDO, the rate-limiting enzyme of the kynurenine pathway. In theory, this could account for increased serotonin as more tryptophan becomes available for serotonin synthesis. However, the downside may be that less NAD and niacin are synthesised downstream, which could exacerbate common psychiatric problems. It is our hypothesis that patients with poor dietary intake, who are treated with antidepressants, are at risk of developing niacin/NAD deficiency with possible development of associated neuropsychiatric symptoms. We therefore propose that niacin supplementation be considered in patients with inadequate diets who are treated with antidepressants. We believe that if this does not happen, a subclinical niacin deficiency may result

  15. Risk of use of antidepressants among children and young adults exposed to the death of a parent

    DEFF Research Database (Denmark)

    Appel, Charlotte Weiling; Johansen, Christoffer; Christensen, Jane

    2016-01-01

    BACKGROUND: Insight into how early parental death impact psychological well-being in children and young adults is important to developing suitable supportive care. The purpose of this study was to investigate the association between early parental death before the child reaches age 30 years......% confidence interval, 1.19, 1.27). We observed stronger associations for women whose parent died by suicide than from other causes, who lost their mother rather than their father, and who lost a parent early rather than later. The increased risk remained more than 2 years from the loss. CONCLUSIONS: Persons...... who lost a parent had an increased risk of use of antidepressants. Subgroups with particularly increased risk, included women, who were bereaved by suicides, who experienced loss of a mother, and who were bereaved when young. The risk of initiating antidepressant use was increased both immediately...

  16. Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods : the example of antidepressant use and the risk of hip fracture

    NARCIS (Netherlands)

    Ali, M Sanni; Groenwold, Rolf H H; Belitser, S.; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Anthonius; Klungel, Olaf H

    2016-01-01

    BACKGROUND: Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and

  17. Pregabalin for the treatment of patients with generalized anxiety disorder with inadequate treatment response to antidepressants and severe depressive symptoms.

    Science.gov (United States)

    Olivares, José M; Álvarez, Enrique; Carrasco, José L; Pérez Páramo, María; López-Gómez, Vanessa

    2015-09-01

    To evaluate the effectiveness of pregabalin in patients with resistant generalized anxiety disorder (GAD) and severe depressive symptoms, we carried out a post-hoc analysis of a multicenter, prospective, and observational 6-month study. We included patients who were at least 18 years old, fulfilled the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for GAD, showed inadequate responses to previous courses of antidepressant treatment, had Montgomery-Asberg Rating Scale scores of at least 35, had not received pregabalin previously, and were prescribed pregabalin upon entry into this study. We included 1815 patients fulfilling the DSM-IV criteria for GAD, and 133 (7.3%) fulfilled the selection criteria for these analyses. Ninety-seven percent of the patients received pregabalin (mean dose: 222 mg/day) in combination with other psychotropics. The Hamilton Anxiety Scale total score was reduced by a mean of 20.3 points (95% confidence interval, 22.1-18.4) (57.2% reduction) at month 6. Pregabalin also ameliorated comorbid depressive symptoms, with a reduction in the mean score of the Montgomery-Asberg Rating Scale of 22.3 points (95% confidence interval, 24.2-20.4) (56.6% reduction). Our results suggest that pregabalin, as part of a combination regimen with antidepressants and/or benzodiazepines, might be effective for the treatment of patients with GAD who have shown inadequate response to previous antidepressants and have severe depressive symptoms.

  18. NF-κB Mediated Regulation of Adult Hippocampal Neurogenesis: Relevance to Mood Disorders and Antidepressant Activity

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    Valeria Bortolotto

    2014-01-01

    Full Text Available Adult hippocampal neurogenesis is a peculiar form of process of neuroplasticity that in recent years has gained great attention for its potential implication in cognition and in emotional behavior in physiological conditions. Moreover, a vast array of experimental studies suggested that adult hippocampal neurogenesis may be altered in various neuropsychiatric disorders, including major depression, where its disregulation may contribute to cognitive impairment and/or emotional aspects associated with those diseases. An intriguing area of interest is the potential influence of drugs on adult neurogenesis. In particular, several psychoactive drugs, including antidepressants, were shown to positively modulate adult hippocampal neurogenesis. Among molecules which could regulate adult hippocampal neurogenesis the NF-κB family of transcription factors has been receiving particular attention from our and other laboratories. Herein we review recent data supporting the involvement of NF-κB signaling pathways in the regulation of adult neurogenesis and in the effects of drugs that are endowed with proneurogenic and antidepressant activity. The potential implications of these findings on our current understanding of the process of adult neurogenesis in physiological and pathological conditions and on the search for novel antidepressants are also discussed.

  19. 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.

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

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    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.