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Sample records for standard antidepressant drugs

  1. Antidepressants and platinum drugs.

    Science.gov (United States)

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

    2014-01-01

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

  2. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2009-08-01

    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  3. Effects of antidepressant drugs on sexual function.

    Science.gov (United States)

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

    1997-01-01

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

  4. Treatment with antiparkinson and antidepressant drugs

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  5. Clinically significant drug interactions with newer antidepressants.

    Science.gov (United States)

    Spina, Edoardo; Trifirò, Gianluca; Caraci, Filippo

    2012-01-01

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

  6. Anti-Depressants, Suicide, and Drug Regulation

    Science.gov (United States)

    Ludwig, Jens; Marcotte, Dave E.

    2005-01-01

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

  7. 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.

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

    Science.gov (United States)

    Eckert, Anne

    2009-06-01

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

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

    Science.gov (United States)

    Man, Colin; Nguyen, Cathina; Lin, Steven

    2014-09-01

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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  11. Acute antidepressant drug administration and autobiographical memory recall

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  12. 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.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Science.gov (United States)

    Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

    2016-09-01

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

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

    International Nuclear Information System (INIS)

    Hall, H.; Oegren, S.O.

    1984-01-01

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

  16. Profitable failure: antidepressant drugs and the triumph of flawed experiments.

    Science.gov (United States)

    McGoey, Linsey

    2010-01-01

    Drawing on an analysis of Irving Kirsch and colleagues' controversial 2008 article in "PLoS [Public Library of Science] Magazine" on the efficacy of SSRI antidepressant drugs such as Prozac, I examine flaws within the methodologies of randomized controlled trials (RCTs) that have made it difficult for regulators, clinicians and patients to determine the therapeutic value of this class of drug. I then argue, drawing analogies to work by Pierre Bourdieu and Michael Power, that it is the very limitations of RCTs -- their inadequacies in producing reliable evidence of clinical effects -- that help to strengthen assumptions of their superiority as methodological tools. Finally, I suggest that the case of RCTs helps to explore the question of why failure is often useful in consolidating the authority of those who have presided over that failure, and why systems widely recognized to be ineffective tend to assume greater authority at the very moment when people speak of their malfunction.

  17. Antidepressant, antioxidant and neurotrophic properties of the standardized extract of Cocos nucifera husk fiber in mice.

    Science.gov (United States)

    Lima, Eliane Brito Cortez; de Sousa, Caren Nádia Soares; Vasconcelos, Germana Silva; Meneses, Lucas Nascimento; E Silva Pereira, Yuri Freitas; Ximenes, Naiara Coelho; Santos Júnior, Manuel Alves; Matos, Natália Castelo Branco; Brito, Rayanne; Miron, Diogo; Leal, Luzia Kalyne Almeida Moreira; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2016-07-01

    The plant Cocos nucifera and its derivatives have shown antidepressant-like effects, although its hydroalcoholic extract has not been studied with this end in mind. Therefore, we decided to determine the antidepressant-like effects of the standardized hydroalcoholic extract of Cocos nucifera husk fiber (HECN) as well as oxidative alterations in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST), and the levels of brain-derived neurotrophic factor (BDNF) in the HC of mice. The extract was characterized based on the content of total polyphenols as well as two phenol compounds-catechin and chlorogenic acid-by HPLC-PDA. Male animals were treated per os (p.o.) for 7 days with distilled water or HECN (50, 100 or 200 mg/kg), or intraperitoneally with vitamin E (Vit E 400 mg/kg). One hour after the last drug administration, the animals were submitted to the open field test, forced swimming test (FST), tail suspension test (TST) and, immediately after the behavioral tests, had their brain removed for neurochemical determinations. The results showed that HECN100 decreased the immobility time in the FST and TST presenting, thus demonstrating an antidepressant-like effect. The administration of HECN decreased malondialdehyde levels in all doses and brain areas studied with the exception of HECN50 in the HC. The administration of HECN also decreased nitrite levels in all doses and brain regions studied. HECN100 also increased the levels of BDNF in HC of mice. In conclusion, we demonstrated that HECN has antidepressant-like properties, probably based on its antioxidant and neurotrophic effects, and is thus relevant for the treatment of depression.

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

    Science.gov (United States)

    Pereira, Vitor Silva; Hiroaki-Sato, Vinícius Antonio

    2018-02-01

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

  19. 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

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Science.gov (United States)

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

    2006-08-01

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

  2. 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

  3. Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models

    Science.gov (United States)

    Noordam, Raymond; Avery, Christy L; Visser, Loes E; Stricker, Bruno H

    2016-01-01

    Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., ‘treated-only design’, statistical power) and we will discuss how specifically drug–gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression. PMID:27248517

  4. Rave drug (ecstasy) and selective serotonin reuptake inhibitor anti-depressants.

    Science.gov (United States)

    Singh, A N; Catalan, J

    2000-04-01

    3, 4 Methylenedioxymethamphetamine (MDMA) also known as Ecstasy is a common recreational drug of abuse and reports of abuse of tricyclic antidepressants are also known. We report two cases of misuse of selective serotonin re-uptake inhibitors (SSRIs) antidepressants in combination with Ecstasy and their beneficial subjective effects experienced by misusers. We hypothesise the probable underlying pharmacological reasons and recommend its use in the treatment of neurotoxic effects of MDMA.

  5. RAVE DRUG (ECSTASY) AND SELECTIVE SEROTONIN REUPTAKE INHIBITOR ANTI-DEPRESSANTS

    OpenAIRE

    Singh, A.N.; Catalan, J.

    2000-01-01

    3, 4 Methylenedioxymethamphetamine (MDMA) also known as Ecstasy is a common recreational drug of abuse and reports of abuse of tricyclic antidepressants are also known. We report two cases of misuse of selective serotonin re-uptake inhibitors (SSRIs) antidepressants in combination with Ecstasy and their beneficial subjective effects experienced by misusers. We hypothesise the probable underlying pharmacological reasons and recommend its use in the treatment of neurotoxic effects of MDMA.

  6. The discovery of antidepressant drugs by computer-analyzed human cerebral bio-electrical potentials (CEEG).

    Science.gov (United States)

    Itil, T M

    1983-01-01

    Antidepressant properties of six compounds were predicted based on their computer-analyzed human electroencephalographical (CEEG) profiles. The clinical investigations with mianserin (GB-94) confirmed the CEEG prediction. This compound has now been marketed as the first antidepressant of which the clinical effects were discovered solely by the quantitative pharmaco-EEG method. As predicted by the CEEG, clinical antidepressant properties of GC-46, mesterolone, and estradiol valerate were observed in preliminary investigations. No extensive studies with definite statistical results were yet carried out with these compounds. No systematic large studies could be conducted with cyclozocine and cyproterone acetate because of the intolerable side effects with these compounds. The optical isomers of mianserin, GF-59 and GF-60, both predicted as antidepressant by the computer EEG data base, have not yet been tested in depressive patients. None of these compounds possess the "typical" pharmacological and/or biochemical profiles of marketed antidepressants. Thus, the discovery of the established antidepressant properties of mianserin (GB-94) by computer analyzed EEG method challenges the well-known biochemical hypotheses of depression and the "classical" development of antidepressant drugs.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Science.gov (United States)

    Yapko, Michael D

    2013-01-01

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

  9. Fear erasure in mice requires synergy between antidepressant drugs and extinction training.

    Science.gov (United States)

    Karpova, Nina N; Pickenhagen, Anouchka; Lindholm, Jesse; Tiraboschi, Ettore; Kulesskaya, Natalia; Agústsdóttir, Arna; Antila, Hanna; Popova, Dina; Akamine, Yumiko; Bahi, Amine; Sullivan, Regina; Hen, René; Drew, Liam J; Castrén, Eero

    2011-12-23

    Antidepressant drugs and psychotherapy combined are more effective in treating mood disorders than either treatment alone, but the neurobiological basis of this interaction is unknown. To investigate how antidepressants influence the response of mood-related systems to behavioral experience, we used a fear-conditioning and extinction paradigm in mice. Combining extinction training with chronic fluoxetine, but neither treatment alone, induced an enduring loss of conditioned fear memory in adult animals. Fluoxetine treatment increased synaptic plasticity, converted the fear memory circuitry to a more immature state, and acted through local brain-derived neurotrophic factor. Fluoxetine-induced plasticity may allow fear erasure by extinction-guided remodeling of the memory circuitry. Thus, the pharmacological effects of antidepressants need to be combined with psychological rehabilitation to reorganize networks rendered more plastic by the drug treatment.

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

    Science.gov (United States)

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

    2013-06-01

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

  11. Geriatric characteristics in randomised controlled trials on antidepressant drugs for older adults: a systematic review

    NARCIS (Netherlands)

    Benraad, Carolien E. M.; Kamerman-Celie, Floor; van Munster, Barbara C.; Oude Voshaar, Richard C.; Spijker, Jan; Olde Rikkert, Marcel G. M.

    2016-01-01

    Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys) function and frailty increase with

  12. Geriatric characteristics in randomised controlled trials on antidepressant drugs for older adults : a systematic review

    NARCIS (Netherlands)

    Benraad, Carolien E. M.; Kamerman-Celie, Floor; van Munster, Barbara C.; Oude Voshaar, Richard C.; Spijker, Jan; Rikkert, Marcel G. M. Olde

    Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys) function and frailty increase with

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

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

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

  14. Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population

    Science.gov (United States)

    Zhong, Wenjun; Kremers, Hilal Maradit; Yawn, Barbara P.; Bobo, William V.; St Sauver, Jennifer L.; Ebbert, Jon O.; Rutten, Lila J.; Jacobson, Debra J.; Brue, Scott M.; Rocca, Walter A.

    2014-01-01

    Purpose To study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately. Methods Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (seven years). We calculated the annual age-and sex-specific prevalence over seven years, and used generalized estimating equation models to test for time trends. Results The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than men consistently across the seven years of the study. The standardized annual prevalence increased from 10.8% in 2005 to 14.4% in 2011 overall, from 7.0% in 2005 to 9.9% in 2011 for men, and from 14.4% in 2005 to 18.6% in 2011 for women. The absolute percent increase was greater in women (4.2% vs. 2.9%; standardized); however, the relative percent increase was greater in men (41.4% vs. 29.2%; standardized). The relative percent increase was greater in the age group 65+ years for both men and women. Conclusions AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women. PMID:25113318

  15. Evaluation of drug interactions in patients treated with antidepressants at a tertiary care cancer center.

    Science.gov (United States)

    Lal, Lincy Subha; Zhuang, Amy; Hung, Frank; Feng, Chun; Arbuckle, Rebecca; Fisch, Michael J

    2012-05-01

    We evaluated potential drug interactions in patients treated with antidepressants at a tertiary care cancer center to determine if it affects resource utilization. We identified a cohort of patients with continuous care at the study institution by tagging patients who received at least three prescriptions for antidepressants within a continuous 6-month period. Data collected included demographics, cancer type and comorbidities, resource utilization (hospital and emergency room visits), and potential major drug interactions. Descriptive statistics and logistic regression were utilized in the analysis. The study population, which included 297 patients, was 70% female and 71% Caucasian; the mean age was 53 years (SD, 12 years), with a mean follow-up period (duration of therapy) of 403 days. Overall, 145 (49%) of the patients had a drug combination that could result in a potential major drug interaction with antidepressants. There were 118 (40%) patients with a potential major drug interaction that could lead to serotonin syndrome symptoms and 59 (20%) patients with a potential major drug interaction with anticoagulants. Potential major drug interactions were associated with an increased number of hospital and ER visits (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.39-4.03). This finding was consistent for the two subanalysis groups as well, serotonin syndrome-inducing drugs (OR, 2.28; 95% CI, 1.33-3.92) and anticoagulants (OR, 3.66; 95% CI, 1.85-7.22). Potential drug interactions are frequent in patients receiving antidepressants in a tertiary care cancer center and are associated with an increase in resource utilization.

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

    Directory of Open Access Journals (Sweden)

    Christos Papandreou

    2009-01-01

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

  17. In vitro effects of three antidepressant drugs on plasma paraoxonase activity.

    Science.gov (United States)

    Saadaoui, Mohamed Hachem; Hellara, Ilhem; Neffati, Fadoua; Mechri, Anouar; Douki, Wahiba; Gaha, Lotfi; Najjar, Mohamed Fadhel

    2012-01-01

    Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to significantly decrease in depressed patients after antidepressant treatment instauration. Our aim was to investigate the in vitro inhibitory effects of three antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity. Plasma from healthy volunteers was spiked with antidepressant drugs. The working solutions were then diluted with plasma to obtain concentrations that covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate after incubation at 37°C for 2 h. Tricyclic antidepressants significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage for imipramine was 15.6% at 100 μg/L after incubation for 1 h (131±1 vs. 155±2 IU/L; p<0.01). At 350 μg/L, the inhibition percentage for imipramine 19.2% after 1 h and 20.2% after 2 h. Amitriptyline was a stronger inhibitor: 26% after 30 min at 125 μg/L. At 250 μg/L, the inhibition percentage for amitriptyline was 36.5% after 30 min (100±4 vs. 159±2 IU/L; p<0.01). The tested tricyclic antidepressants significantly inhibit PON1 activity in a concentration-dependent manner. Amitriptyline had a higher inhibition potency than imipramine.

  18. Antidepressant drugs and the risk of suicide in children and adolescents.

    Science.gov (United States)

    Isacsson, Göran; Rich, Charles L

    2014-04-01

    Government agencies have issued warnings about the use of antidepressant medications in children, adolescents, and young adults since 2003. The statements warn that such medications may cause de novo 'suicidality' in some people. This review explores the data on the treatment of depression that led to these warnings and subsequent data that are relevant to the warnings. It also addresses the effectiveness of antidepressant treatment in general and the relationship of suicide rates to antidepressant treatment. It concludes that the decisions for the 'black box' warnings were based on biased data and invalid assumptions. Furthermore, the decisions were unsupported by the observational data regarding suicide in young people that existed in 2003. The following recommendations would seem to follow from these observations. First, drug authorities should re-evaluate the basis for their imposed warnings on antidepressant medicines, and analyze the actual public health consequences the warnings have had. In the absence of substantial evidence supporting the warnings, they should be removed. Second, physicians and other providers with prescription privileges should continue to be educated regarding the importance of aggressively treating depression in young people, using antidepressants when indicated. Third, physicians and other professionals who treat depressed young people must always be aware of the risk of suicide (albeit quite low) and observe them closely for any signs of increased risk of suicide. This is necessary regardless of the type of treatment being provided.

  19. Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

    Directory of Open Access Journals (Sweden)

    Juan Carlos Martínez-Aguayo

    2016-06-01

    Full Text Available ABSTRACT Background The United States Food and Drug Administration (FDA has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI and venlafaxine in children and adolescents. Objectives To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

  20. 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

  1. Antidepressant effect and pharmacological evaluation of standardized extract of flavonoids from Byrsonima crassifolia.

    Science.gov (United States)

    Herrera-Ruiz, M; Zamilpa, A; González-Cortazar, M; Reyes-Chilpa, R; León, E; García, M P; Tortoriello, J; Huerta-Reyes, M

    2011-11-15

    Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg. Copyright © 2011 Elsevier GmbH. All rights reserved.

  2. Iatrogenic Cushing's syndrome with inhaled steroid plus antidepressant drugs.

    Science.gov (United States)

    Celik, Ozlem; Niyazoglu, Mutlu; Soylu, Hikmet; Kadioglu, Pinar

    2012-08-29

    Current guidelines recommend the use of inhaled corticosteroids (ICS) for suppression of airway inflammation in patients with asthma. Although it is well known that ICS cause dose-related adrenocortical suppression, it is less known that they can lead to iatrogenic Cushing's syndrome (CS). Fluticasone propionate (FP) is an ICS more potent than beclomethasone and budesonide. FP is metabolized as mediated by cytochrome P450 3A4 in the liver and the gut. Systemic bioactivity of FP can increase with the use of drugs that affect the cytochrome P450. Herein, we report the rapid development of iatrogenic CS in a patient receiving paroxetine and mirtazepine for 12 weeks in addition to inhaled FP.

  3. Effects of self-aggregation on the hydration of an amphiphilic antidepressant drug in different aqueous media

    International Nuclear Information System (INIS)

    Taboada, Pablo; Gutierrez-Pichel, Manuel; Mosquera, Victor

    2004-01-01

    Apparent molal volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic antidepressant drug clomipramine hydrochloride have been determined from density and ultrasound velocity measurements in the temperature range 288.15-313.15 K in buffered aqueous solution of pH 3.0 and 5.5. Critical concentrations of aggregation of this drug were obtained from inflections on the plots of the sound velocity against drug concentration. Apparent molal adiabatic compressibilities of the aggregates formed by the drug, calculated by combining the ultrasound velocity and density data, were typical of those for a stacked aggregate. From the temperature dependence of the critical concentration and using the mass action model combined with the Phillips definition of the critical concentration the thermodynamic standard quantities: free Gibbs energy, enthalpy and entropy of aggregate formation were calculated. The critical concentration and energy involved in the aggregation process of this drug have been also evaluated experimentally using isothermal titration calorimetry at 298.15 K. The solvent-drug interactions have been discussed from compressibility and calorimetry data

  4. Impact of drug cost sharing on service use and adverse clinical outcomes in elderly receiving antidepressants.

    Science.gov (United States)

    Wang, Philip S; Patrick, Amanda R; Dormuth, Colin; Maclure, Malcolm; Avorn, Jerry; Canning, Claire F; Schneeweiss, Sebastian

    2010-03-01

    Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance. To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+. Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models. Neither policy affected the rates of visits to

  5. Blonanserin – A Novel Antianxiety and Antidepressant Drug? An Experimental Study

    Science.gov (United States)

    Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

    2016-01-01

    Introduction Many psychiatric disorders show signs and symptoms of anxiety and depression. A drug with both, effects and lesser adverse effects is always desired. Blonanserin is a novel drug with postulated effect on anxiety and depression. Aim The study was aimed to evaluate the effect of Blonanserin on anxiety and depression in animal models. Materials and Methods By using elevated plus maze test and forced swimming test, the antianxiety and antidepressant effects were evaluated. Animal ethics protocols were followed strictly. Total 50 rats (10 rats per group) were used for each test. As a control drug diazepam and imipramine were used in elevated plus maze and forced swimming test respectively. Blonanserin was tested for 3 doses 0.075, 0.2 and 0.8mg. These doses were selected from previous references as well as by extrapolating human doses. Results This study showed an antianxiety effect of Blonanserin comparable to diazepam, which was statistically significant. Optimal effect was observed with 0.075mg, followed by 0.2 and 0.8mg. It also showed an antidepressant effect which was statistically significant. Optimal effect was observed at 0.2mg dose. Conclusion The results showed that at a dose range of 0.075 and 0.2mg Blonanserin has potential to exert an adjuvant antianxiety and antidepressant activity in animal models. In order to extrapolate this in patient, longer clinical studies with comparable doses should be planned. The present study underlines potential of Blonanserin as a novel drug for such studies. PMID:27790460

  6. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy

    Science.gov (United States)

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi AJO; Moriguchi-Jeckel, Cristina M; de Vries, Erik FJ

    2017-01-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants. PMID:28653857

  7. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Selective inhibitors of the human serotonin transporter (hSERT) have been first-line treatment against depression for several decades. Recently, vortioxetine was approved as a new therapeutic option for the treatment of depression. Vortioxetine represents a new class of antidepressant drugs...... with a multimodal pharmacological profile that in addition to potent inhibition of hSERT include agonistic or antagonistic effects at different serotonin receptors. We used a combination of computational, chemical, and biological methods to decipher the molecular basis for high affinity binding of vortioxetine in h...

  9. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects?

    Science.gov (United States)

    Raeder, Maria B; Fernø, Johan; Vik-Mo, Audun O; Steen, Vidar M

    2006-09-01

    Drug-induced weight gain is a major problem in the treatment of psychiatric disorders, especially with some antipsychotic- and antidepressant drugs. We have recently demonstrated that antipsychotic- and antidepressant drugs activate the SREBP (sterol regulatory element-binding proteins) transcription factors in human- and rat glial cells, with subsequent up-regulation of downstream genes involved in cholesterol- and fatty acid biosynthesis. Since stimulation of cellular lipogenesis in the liver could be of relevance for the metabolic side effects of these drugs, we have now investigated the effects of antidepressants, antipsychotic- and mood-stabilizing drugs on cell cultures of human liver cells. For several of the drugs being strongly associated with weight gain (clozapine, imipramine, and amitriptyline), we observed a very pronounced activation of SREBP. Ziprasidone and buproprion, however, which are not associated with weight gain, did hardly stimulate the SREBP system. For haloperidol, olanzapine and mirtazapine, the correspondence between metabolic side effects and SREBP stimulation in liver cells was less obvious. The mood-stabilizers did not increase SREBP activation. The results indicate a relationship between drug-induced activation of SREBP in cultured human liver cells and weight gain side-effects of antidepressant and antipsychotic drugs.

  10. 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 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.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.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.

  11. Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

    International Nuclear Information System (INIS)

    Garcia-Sevilla, J.A.; Zis, A.P.; Hollingsworth, P.J.; Greden, J.F.; Smith, C.B.

    1981-01-01

    The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors

  12. Frequency of different anti-depressants associated with suicides and drug deaths.

    Science.gov (United States)

    Drasch, Gustav; Dahlmann, Felicitas; von Meyer, Ludwig; Roider, Gabriele; Eisenmenger, Wolfgang

    2008-03-01

    From each case of suicide and drug-related death autopsied in the Institute of Forensic Medicine, Munich during the years 2001--2005, a toxicological investigation on anti-depressants (AD) was performed. In 180 suicides and 72 narcotic drug death cases, ADs were detected: 4 different classic tricyclic anti-depressants (TCAs), 6 other non-selective monoamine re-uptake inhibitors (NSMRIs), 5 selective serotonin re-uptake inhibitors (SSRIs) and 3 other ADs. The suicides were grouped further according to the type of suicide (violent or non-violent). The prescription frequency of the ADs in Germany, expressed as the defined daily dosages (DDDs), during the investigated years served for comparison. There were serious differences in the frequency of different ADs regarding to the manner of suicide. In cases associated with doxepin and trimipramine, non-violent suicides were distinctly over-represented, as in cases in which the drug itself was responsible for the death as in cases of non-violent suicides in other manners. In contrast, in cases with citalopram or opipramol, violent forms of suicides were significantly over-represented. For amitriptyline, the ratio was approximately balanced. For the remainder of the ADs, the case numbers were too low for a valid evaluation. The different frequency distributions of the ADs, associated with violent and non-violent suicides may be explained by their different pharmacological active profiles and the different lethality of overdoses of the different ADs. There was no indication at all for a special suicidal problem of SSRIs in juveniles. Amongst 1,127 suicides within 5 years, in an area with approximately 5 million people, the youngest suicide victim with SSRIs was 28 years old. In drug death cases, citalopram was obviously over-represented.

  13. Quality of antidepressant drugs research articles published in Indian medical journals.

    Science.gov (United States)

    Charan, Jaykaran; Saxena, Deepak; Yadav, Preeti; Kantharia, N D

    2011-07-01

    Quality of methodological and statistical parameters published in various Indian Medical Journals are usually debated in terms of appropriateness. Aim of this manuscript is to analyze and validate efficacy studies on antidepressant drugs published in Indian Medical Journals regarding quality of various methodological and statistical parameters used. An in-depth review of Efficacy studies on Antidepressant published in Indian Medical Journals was conducted. Articles were retrieved from all possible sources like Published Journals, downloaded through Pubmed, MedInd, Opengate, Medknow, and Cochrane. These studies were analyzed and validated for various methodological and statistical parameters. Descriptive statistics for various parameters with confidence interval (CI) is also reported herewith. Of 32 articles reviewed, primary and secondary endpoints and sample size calculation was reported in only one article (3.1%; 95% CI, 0.5 to 15.7%). Power and CI was not reported in any of the reviewed articles. Inclusion and exclusion criteria were reported in 9 (28.3%; 95% CI, 15.5 to 45.3%) articles. Information regarding randomization was mentioned in 12 (37.5%; 95% CI, 22.9 to 54.7%) articles, whereas reporting of blinding or open label status of the study was mentioned in 21 (65.6%; 95% CI, 48.3 to 79.5%) articles. Assumptions of statistical tests were not reported in any of the reviewed articles. Statistical tests were used in only 14 (43.7%; 95% CI, 28.1 to 60.6%) articles of which 70% of were inappropriate. All studies were underpowered for small and medium effect size. Quality of reporting of methodological and statistical aspects of antidepressant efficacy studies published in Indian medical journals are poor and hence makes difficult to conclude on issues related to validity of these studies.

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  15. Differential blockade of neuronal voltage-gated Na(+) and K(+) channels by antidepressant drugs.

    Science.gov (United States)

    Nicholson, Graham M; Blanche, Tim; Mansfield, Kylie; Tran, Yvonne

    2002-09-27

    The effects of a range of antidepressants were investigated on neuronal voltage-gated Na(+) and K(+) channels. With the exception of phenelzine, all antidepressants inhibited batrachotoxin-stimulated 22Na(+) uptake, most likely via negative allosteric inhibition of batrachotoxin binding to neurotoxin receptor site-2 on the Na(+) channel. Imipramine also produced a differential action on macroscopic Na(+) and K(+) channel currents in acutely dissociated rat dorsal root ganglion neurons. Imipramine produced a use-dependent block of Na(+) channels. In addition, there was a hyperpolarizing shift in the voltage-dependence of steady-state Na(+) channel inactivation and slowed repriming kinetics consistent with imipramine having a higher affinity for the inactivated state of the Na(+) channel. At higher concentrations, imipramine also blocked delayed-rectifier and transient outward K(+) currents in the absence of alterations to the voltage-dependence of activation or the kinetics of inactivation. These actions on voltage-gated ion channels may underlie the therapeutic and toxic effects of these drugs. Copyright 2002 Elsevier Science B.V.

  16. Development and evaluation of gastroretentive floating tablets of an antidepressant drug by thermoplastic granulation technique

    Directory of Open Access Journals (Sweden)

    Harshal Ashok Pawar

    2014-06-01

    Full Text Available The present study was undertaken with an aim to formulate, develop and evaluate gastroretentive floating tablets of an antidepressant drug, Venlafaxine HCl (hydrochloride, which release the drug in a sustained manner over a period of 24 h. Three different hydrophobic retardants namely hydrogenated cottonseed oil, carnauba wax, cetyl alcohol and a hydrophilic polymer Methocel® (hydroxy propyl methyl cellulose (HPMC K15M were used in different combinations at different ratios for the preparation of tablets. The tablets were prepared by Hot Melt or Thermoplastic granulation method and evaluated for tablet thickness, hardness, weight variation, friability, floating lag time and in vitro drug release. Formulation F8 with hydrophilic polymer (Methocel® K15M and hydrophobic retardant (carnauba wax in the ratio 1:2.6 (approx. was considered as an optimized formulation. The optimized formulation showed satisfactory sustained drug release and remained buoyant on the surface of the medium for more than 24 h and its release profile was comparable with the marketed formulation (VENTAB-XL 37.5. It can also be concluded that floating drug delivery system of Venlafaxine HCl can be successfully formulated as an approach to increase gastric residence time and thereby improving its bioavailability.

  17. I-125-labelled iodothyronines: useful tools for studies of effects of an antidepressant drug fluoxetine in the rat

    Czech Academy of Sciences Publication Activity Database

    Pavelka, Stanislav

    2010-01-01

    Roč. 286, č. 3 (2010), s. 867-871 ISSN 0236-5731 R&D Projects: GA ČR(CZ) GA304/08/0256 Institutional research plan: CEZ:AV0Z50110509 Keywords : antidepressant drug * radiometric enzyme assay * thyroid hormone Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 0.777, year: 2010

  18. Genetically encoded photocrosslinkers locate the high-affinity binding site of antidepressant drugs in the human serotonin transporter

    DEFF Research Database (Denmark)

    Rannversson, Hafsteinn; Andersen, Jacob; Hall, Lena Sørensen

    2016-01-01

    Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode...

  19. Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study

    OpenAIRE

    Shin, Ju-Young; Park, Mi-Ju; Lee, Shin Haeng; Choi, So-Hyun; Kim, Mi-Hee; Choi, Nam-Kyong; Lee, Joongyub; Park, Byung-Joo

    2015-01-01

    Objective To define the risk of intracranial haemorrhage among patients treated with antidepressants and non-steroid anti-inflammatory drugs (NSAIDs), compared with the risk among those treated with antidepressants without NSAIDs. Design Retrospective nationwide propensity score matched cohort study. Setting Korean nationwide health insurance database between 1 January 2009 and 31 December 2013. Participants Patients who began receiving antidepressants for the first time (index date) without ...

  20. Clinical perspectives on the influence of drug formulation on patient tolerability and use of commonly prescribed antidepressants in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Matthew A Fuller

    2013-01-01

    Full Text Available The purpose of this review is to summarize the formulation options for currently available antidepressants, and discuss examples of the influence that formulation may have on the pharmacologic and clinical profiles of the medications. A review of current literature suggests that differences in drug-delivery technologies can lead to variations in the pharmacokinetic and pharmacodynamic profiles of generic and branded drugs, despite generic drugs being required to meet bioequivalence standards compared with their branded counterparts. These differences may influence the effectiveness and tolerability of treatment. Recent reports have highlighted the need for individualized treatment regimens and careful assessment of tolerability and efficacy when switching patients from brand to generic formulations. There is a growing body of evidence indicating that differences in formulation can substantially impact drug pharmacokinetics and pharmacodynamics, which in turn, can affect drug effects. The clinical impact of these differences remains unclear. Further research is needed to clarify the influence of antidepressant formulations on treatment adherence, patient preference, and quality of life, and how this impacts clinical practice with regard to brand versus generic treatment selection.

  1. Tricyclic Antidepressants

    Science.gov (United States)

    Schmidt, Gary J.

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

  2. Optical sensors for therapeutic drug monitoring of antidepressants for a better medication adjustment

    Science.gov (United States)

    Krieg, Anne K.; Hess, Stefan; Gauglitz, Günter

    2013-05-01

    Therapeutic drug monitoring provides the attending physicians with detailed information on a patient's individual serum level especially during long-term medication. Due to the fact that each patient tolerates drugs or their metabolites differently a medication adjustment can reduce the number and intensity of noticeable side-effects. In particular, psychotropic drugs can cause unpleasant side-effects that affect a patient's life almost as much as the mental disease itself. The tricyclic antidepressants amitriptyline is commonly used for treatment of depressions and was selected for the development of an immunoassay using the direct optical sensor technique Reflectometric Interference Spectroscopy (RIfS). RIfS is a simple, robust and label-free method for direct monitoring of binding events on glass surfaces. Binding to the surface causes a shift of the interference spectrum by a change of the refractive index or physical thickness. This technique can be used for time-resolved observation of association and dissociation of amitriptyline (antigen) and a specific antibody using the binding inhibition test format. An amitriptyline derivative is immobilized on the sensor surface and a specific amount of antibodies can bind to the surface unless the binding is inhibited by free amitriptyline in a sample. No fluorescent label is needed making the whole assay less expensive than label-based methods. With this recently developed immunoassay amitriptyline concentrations in buffer (PBS) can easily be detected down to 500 ng/L.

  3. Magnetic micro-solid-phase extraction based on magnetite-MCM-41 with gas chromatography-mass spectrometry for the determination of antidepressant drugs in biological fluids.

    Science.gov (United States)

    Kamaruzaman, Sazlinda; Sanagi, Mohd Marsin; Yahaya, Noorfatimah; Wan Ibrahim, Wan Aini; Endud, Salasiah; Wan Ibrahim, Wan Nazihah

    2017-11-01

    A new facile magnetic micro-solid-phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite-MCM-41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 μg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite-MCM-41 at pH 12. The analyte was desorbed using 100 μL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05-500 μg/L (r 2  = 0.996-0.999). Good limits of detection (0.008-0.010 μg/L) were obtained for the analytes with good relative standard deviations of drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1-115.4%. Results indicate that magnetite micro-solid-phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Drugs with antidepressant properties affect tryptophan metabolites differently in rodent models with depression-like behavior.

    Science.gov (United States)

    Eskelund, Amanda; Li, Yan; Budac, David P; Müller, Heidi K; Gulinello, Maria; Sanchez, Connie; Wegener, Gregers

    2017-07-01

    The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression, and its controls: Flinders Sensitive Line and Sprague-Dawley rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains. Furthermore, effects of vortioxetine on tryptophan metabolites were assessed in the cortical regions of lupus mice (MRL/MpJ-Fas Ipr ), a murine model of increased depression-like behavior associated with inflammation. Sustained vortioxetine or fluoxetine (at doses aimed to fully occupy serotonin transporter via food or drinking water for at least 14 days) reduced levels of the excitotoxin quinolinic acid (QUIN) in various brain regions in all rats. Furthermore, chronic vortioxetine reduced levels of QUIN in MRL/MpJ-Fas Ipr mice. Acute i.p. administration of fluoxetine (10 mg/kg) or vortioxetine (10 mg/kg) led to reduced brain 5-hydroxyindoleacetic acid in Sprague-Dawley rats (2, 4, 6, and 8 h) and a similar trend was evident in Flinders Sensitive Line and Flinders Sensitive Line rats after 4 h. In contrast, single or repeated administration of ketamine (15 mg/kg i.p.) did not induce significant changes in metabolite levels. In conclusion, sustained vortioxetine and fluoxetine administration decreased QUIN independent of species, while ketamine was ineffective. These results support the hypothesis that modulating tryptophan metabolism may be part of the mechanism of action for some antidepressants. © 2017 International Society for Neurochemistry.

  5. Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

    Science.gov (United States)

    2011-01-01

    Background In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD. Methods/Design The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence. Discussion This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates

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

    NARCIS (Netherlands)

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

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

  7. SEXUAL DYSFUNCTION INDUCED BY ANTI-PSYCHOTICS AND ANTI-DEPRESSANTS IN DRUG NAIVE PATIENTS – A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    M. Mohanalakshmi

    2017-03-01

    Full Text Available BACKGROUND The aim of this study was to determine and compare sexual dysfunction caused by anti-psychotics and anti-depressants in drug naïve patients. MATERIALS AND METHODS Patients diagnosed as drug naïve schizophrenic and depression as per DSM-5 criteria & age between 18-45 years were recruited and allocated into group A (n=30–receiving anti-psychotics & group B (n=30 receiving anti-depressants after informed consent by the patients. Sexual dysfunction was assessed by Arizona Sexual Experiences Scale (ASEX during the initial 2 months of therapy. RESULTS ASEX mean for patients receiving antipsychotics increased from the baseline of 7.97 to 17.23 and the ASEX mean for patients receiving antidepressants increased from baseline of 7.80 to 18.67 with p value of 0.249 which is not statistically significant. Among the antipsychotics haloperidol ASEX mean increased from 7.87 to 18.00 and risperidone mean increased from 8.07 to 16.47 with the p value of 0.335 which is not significant. More patients on haloperidol showed evidence of sexual dysfunction as assessed by ASEX scoring than risperidone though p value was not significant. Among the two antidepressants ASEX score mean for amitriptyline patients increased from 8.07 to 16.47, and that of fluoxetine from 7.53 to 16.47 with the p value of 0.018* statistically significant at α of 0.05 level. CONCLUSION This study shows presence of sexual dysfunction in patients receiving antipsychotics & antidepressants by 2 nd month of therapy though statistically not significant. Fluoxetine group patients developed statistically significant sexual dysfunction. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account because this side effect adds to the emotional stress and worsening of mental dysfunction.

  8. Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action.

    Science.gov (United States)

    Cerit, Hilâl; Veer, Ilya M; Dahan, Albert; Niesters, Marieke; Harmer, Catherine J; Miskowiak, Kamilla W; Rombouts, Serge A R B; Van der Does, Willem

    2015-12-01

    Studies on the neural effects of Erythropoietin (EPO) indicate that EPO may have antidepressant effects. Due to its hematopoietic effects, EPO may cause serious side-effects with repeated administration if patients are not monitored extensively. ARA290 is an EPO-analog peptide without such hematopoietic side-effects but may have neurotrophic and antidepressant effects. The aim of this study was to investigate the possible antidepressant effects of ARA290 in a neuropsychological model of drug action. Healthy participants (N=36) received ARA290 (2mg) or placebo in a double-blind, randomized, parallel-group design. Neural and cognitive effects were assessed one week after administration. Primary outcome measures were the neural processing of fearful vs happy faces and the behavioral recognition of emotional facial expressions. ARA290-treated individuals displayed lower neural responses to happy faces in the fusiform gyrus. ARA290 tended to lower the recognition of happy and disgust facial expressions. Although ARA290 was not associated with a better memory for positive words, it was associated with faster categorization of positive vs negative words. Finally, ARA290 increased attention towards positive emotional pictures. No effects were observed on mood and affective symptoms. ARA290 may modulate some aspects of emotional processing, however, the direction and the strength of its effects do not unequivocally support an antidepressant-like profile for ARA290. Future studies may investigate the effects of different timing and dose. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  9. Spadin, a Sortilin-derived peptide: a new concept in the antidepressant drug design

    Directory of Open Access Journals (Sweden)

    Heurteaux Catherine

    2011-07-01

    Full Text Available Depression is the most common of psychiatric illnesses. The design of effective treatments for this disorder is a challenging process. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. Deletion of TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate the fast antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the sortilin receptor and acting through TREK-1 inhibition.

  10. The effect of anti-depressant and narcoleptic drugs on isopropyl iodoamphetamine biodistribution

    International Nuclear Information System (INIS)

    Moretti, J.L.; Holman, B.L.; Delmon, L.; Carmel, A.; Johnson, D.; Moingeon, P.; Blau, M.; Chu, H.

    1985-01-01

    I-123 Nisopropyl p-iodoamphetamine (IMP) is a useful radiotracer for imaging regional cerebral perfursion in a wide variety of neurological and cerebrovascular diseases. The major route of amine metabolism in the lung is the mixed function oxidase (MFO) system. A number of antidepressants and narcoleptic agents have been shown to displace amphetamine from the lung. If these drugs release IMP before it is metabolized to lipophobic products, brain concentration will be affected. The authors investigated the effects of these drugs on IMP distribution in animals with high and low pulmonary concentrations of MFO. When 1 mg/kg imipramine (IM) was injected iv into Wistar rats 30 min before IMP and 50 min before sacrifice, lung activity was depressed (4 + 1% ID vs 12 + 4% ID). Brain activity was depressed only with 4 mg/kg IM (l.5 + .3% ID vs 2.7 + .7% ID). There was no significant difference in IMP brain activity without IM and when IM was given simultaneously with, 5 or 15 min after IMP. In New Zealand rabbits which have a low pulmonary MFO concentration, IM altered lung and brain uptake during simultaneous injection and as late as 15 min after IMP. Lung uptake was reduced 51% and brain uptake was increased 25%, 20%, and 19% when IM was injected 0, 5 and 15 min after IMP. The MAO inhibitors, phenelzine and L deprenyl, did not alter the brain, lung or liver IMP activity in rats at a dose of 5 mg/kg. These data are consistent with a model in which IMP is trapped and metabolized in the lung by the MFO system. Assuming an active MFO system in the human (unlike the rabbit), brain activity of IMP will not be altered by either IM or MAO inhibitors

  11. 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.

  12. New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs.

    Science.gov (United States)

    Mandrioli, Roberto; Protti, Michele; Mercolini, Laura

    2018-01-01

    New-generation antidepressants (NGAs) are the latest additions to the clinician's arsenal in the fight against depression. After the introduction of selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups followed, identified by their main mechanisms of activity: serotonin and norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators (SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and selective serotonergic antidepressants (NaSSA); norepinephrine reuptake inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors (SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists (MaSA). Although SSRIs are still the most widely used and well known NGAs, the other groups are increasingly being used in the current therapeutic settings obtaining comparable clinical results, and with tolerability and safety profiles that can often provide significant advantages over those of SSRIs. Scopus and PubMed databases were searched for the most significant papers centered on the medicinal chemistry, pharmacodynamics, pharmacokinetics and analysis in human biological fluids of the following antidepressants: venlafaxine, duloxetine, milnacipran, trazodone, vortioxetine, vilazodone. The main characteristics of commercially available non-SSRI NGAs (belonging to the SNRI, SARI and SMS classes) are described, focusing on the role of analytical methods that can be applied to perform therapeutic drug monitoring (TDM), but also including drug pharmacokinetics, metabolism and interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Classical neurotransmitters and neuropeptides involved in major depression in a multi-neurotransmitter system: a focus on antidepressant drugs.

    Science.gov (United States)

    Werner, Felix-Martin; Coveñas, R

    2013-01-01

    We summarize the alterations of classical neurotransmitters and neuropeptides and the corresponding subreceptors involved in major depression. Neuronal circuits in the brainstem, hippocampus and hypothalamus are developed, since they can be used to derive a multimodal pharmacotherapy. In this sense, serotonin hypoactivity could occur through a strong presynaptic inhibition of glutaminergic neurons via the subtype 5 of metabotropic glutaminergic receptors, and noradrenaline hypoactivity could be due to an enhanced presynaptic inhibition of GABAergic neurons via GABAB receptors. In the hippocampus, dopamine hypoactivity leads to a decreased positive effect. In clinical trials, the antidepressant effect of drugs interfering with the mentioned subreceptors, for example the triple reuptake inhibitor amitifadine, is being investigated. Moreover, the alterations of neuropeptides, such as corticotropin-releasing hormone, neuropeptide Y and galanin are pointed out. The additional antidepressant effect of analogs, agonists and antagonists of the mentioned neuropeptides should be examined.

  14. Hollow fiber-based liquid phase microextraction combined with high-performance liquid chromatography for extraction and determination of some antidepressant drugs in biological fluids.

    Science.gov (United States)

    Esrafili, Ali; Yamini, Yadollah; Shariati, Shahab

    2007-12-05

    The applicability of hollow fiber-based liquid phase microextraction (HF-LPME) was evaluated for the extraction and preconcentration of three antidepressant drugs (amitriptyline, imipramine and sertraline) prior to their determination by HPLC-UV. The target drugs were extracted from 11.0 mL of aqueous solution with pH 12.0 (source phase) into an organic extracting solvent (n-dodecane) impregnated in the pores of a hollow fiber and finally back extracted into 24 microL of aqueous solution located inside the lumen of the hollow fiber and adjusted to pH 2.1 using 0.1M of H3PO4 (receiving phase). The extraction was performed due to pH gradient between the inside and outside of the hollow fiber membrane. In order to obtain high extraction efficiency, the parameters affecting the HF-LPME including pH of the source and receiving phases, the type of organic phase, ionic strength and volume of the source phase, stirring rate and extraction time were studied and optimized. Under the optimized conditions, enrichment factors up to 300 were achieved and the relative standard deviation (R.S.D.%) of the method was in the range of 2-12%. The calibration curves were obtained in the range of 5-500 microg L(-1) with reasonable linearity (R2>0.998) and the limits of detection (LODs) ranged between 0.5 and 0.7 microg L(-1) (based on S/N=3). Finally, the applicability of the proposed method was evaluated by extraction and determination of the drugs in urine, plasma and tap water samples. The results indicated that hollow fiber microextraction method has excellent clean-up and high-preconcentration factor and can be served as a simple and sensitive method for monitoring of antidepressant drugs in the biological samples.

  15. [Antidepressants in epilepsy].

    Science.gov (United States)

    Castaño-Monsalve, Beatriz

    2013-08-01

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

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

    Directory of Open Access Journals (Sweden)

    A.R. Yavarikia

    2007-07-01

    Full Text Available Introduction & Objectives: Low back pain (LBP is one of common medical problems with several accepted medical modalities such as drugs, physiotherapy, surgery, etc. We studied the efficacy of tricyclic antidepressant (TCA, and tricyclic antidepressant plus non steroidal anti inflammatory drugs (TCA + NSAID in 200 patients with chronic LBP. Materials & Methods: In an experimental clinical trial study on patients with chronic low back pain without organic findings, patients were divided in two groups of 100 cases. At certain times the response to treatment protocols were collected and compared using VAS system. Patient’s data including age, sex, smoking and response to treatment were recorded and analyzed using chi-square, t-tests, ANOVA and SPSS software. Results: 83 (41.5% of patients were males and 117 (58.5% were females. The age range was 21 to 75 (mean age 43.1 14.1y there was no meaning full statistical difference in demographic characteristics such as age, sex (respectively p=0.66, p=0.78 the ultimate pain was less (p0.05.Conclusion: TCA prescription is an efficient method of treatment of low back pain with or with out NSAIDS. But using NSAID+TCA will be almost more powerful and efficient method in the long term period.

  17. The male heart and the female mind: a study in the gendering of antidepressants and cardiovascular drugs in advertisements in Irish medical publication.

    Science.gov (United States)

    Curry, Phillip; O'Brien, Marita

    2006-04-01

    Stereotypes which suggest that cardiovascular disease and depression are related to gender can have consequences for the mental and physical health outcomes of both men and women. This study examines how these stereotypes may be reinforced by medical publications advertising for cardiovascular and antidepressant medication. A random sample of 61 (with no repeats) advertisements which appeared in Irish medical publications between July 2001 and December 2002 were analysed using both content and semiotic analysis. Results indicate that the meanings created by advertisers for cardiovascular drugs and antidepressants did in fact gender these products. Women were depicted as the predominant users of antidepressants and men as the main users of cardiovascular drugs. The images used identified two stereotyped patients: the 'male' heart patient and the depressed 'female' patient. Furthermore, the imagery and language used to promote the two categories of medication tended to strengthen gendered associations.

  18. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-02

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  19. Standardization Study of Antifertility Drug - Pippalyadiyoga

    Directory of Open Access Journals (Sweden)

    D. Shaila

    2005-01-01

    Full Text Available The present paper deals with the standardization study of pippalyadiyoga powder. It is used as a long acting contraceptive. The standardization of compound drug has been achieved by physico-chemical analysis and high performance liquid chromatography (HPLC fingerprint studies. Quantitative evaluation of borax in pippalyadiyoga showed 19.08% as sodium borate. RP-HPLC was performed using methanol and water as mobile phase. The detection and quantification was performed at a wavelength of 345 nm. Linearity of detector response for piperine was between the concentrations 0.005% to 0.1%. The correlation coefficient obtained for the linearity was 0.998. The recovery value of standard piperine was 99.4%. Low value of standard deviation and coefficient of variation are indicative of high precision of the method. Quantitative evaluation of piperine in pippalyadiyoga was found to be 0.339%.

  20. Emergency Department Visits for Drug-Related Suicide Attempts Involving Antidepressants by Adolescents and Young Adults: 2004 to 2008. The DAWN Report

    Science.gov (United States)

    Substance Abuse and Mental Health Services Administration, 2011

    2011-01-01

    In 2008, adolescents made 23,124 visits to the emergency department (ED) for drug-related suicide attempts, and young adults made 38,036 such visits; of these visits, 23.0 percent (5,312 visits) among adolescents and 17.6 percent (6,700 visits) among young adults involved antidepressants. Among ED visits for suicide attempts involving…

  1. Interaction between methylphenidate, methadone and different antidepressant drugs on antinociception in mice, and possible clinical implications.

    Science.gov (United States)

    Schreiber, Shaul; Bader, Miaad; Rubovitch, Vardit; Pick, Chaim G

    2017-06-01

    Methylphenidate (MPH), a psychostimulant used for treatment of attention deficit hyperactivity disorder (ADHD), is widely used by patients on antidepressants and methadone maintenance treatment (MMT). Preclinical studies showed MPH to exert analgesic effects when given alone or with morphine. Using the hotplate assay on mice, we studied the interaction of acute doses of MPH with sub-threshold doses of methadone and different antidepressant medications and the interaction of increasing doses of MPH with chronic methadone. Adding a sub-threshold dose of venlafaxine, desipramine or clomipramine to MPH produced significant augmentation of MPH antinociception with each medication (P methadone. However, addition of increasing doses of MPH to chronic methadone given for 2 weeks using ALZET osmotic mini pumps induced augmentation of the antinociceptive effect of chronic methadone exclusively at high dose of MPH (7.5 mg/kg). These findings may implicate the need of an excessive attention to the administration of MPH to MMT patients. The no interaction found between MPH and escitalopram may hint to the possibly safe co-administration of MPH and selective serotonin reuptake inhibitors (SSRIs) to depressed ADHD patients. Further studies are needed in order to validate these possible clinical implications.

  2. Involvement of monoaminergic systems in anxiolytic and antidepressive activities of the standardized extract of Cocos nucifera L.

    Science.gov (United States)

    Lima, Eliane Brito Cortez; de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; E Silva Pereira, Yuri Freitas; Matos, Natália Castelo Branco; de Freitas, Rayanne Brito; Lima, Nycole Brito Cortez; Patrocínio, Manoel Cláudio Azevedo; Leal, Luzia Kalyne Almeida Moreira; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

    2017-01-01

    Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments. The forced swimming test was performed with dopaminergic and noradrenergic antagonists, as well as a serotonin release inhibitor. Administration of HECN in the FST after intraperitoneal (i.p.) pretreatment of mice with sulpiride (50 mg/kg), prazosin (1 mg/kg), or p-chlorophenylalanine (PCPA, 100 mg/kg) caused the actions of these three agents to be reversed. However, this effect was not observed after pretreating the animals with SCH23390 (15 µg/kg, i.p.) or yohimbine (1 mg/kg, i.p.) The dose chosen for HECN was 100 mg/kg, p.o., which increased the number of entries as well as the permanence in the open arms of the maze after acute and repeated doses. In both the forced swimming and the tail suspension tests, the same dose decreased the time spent immobile but did not disturb locomotor activity in an open-field test. The anxiolytic effect of HECN appears to be related to the GABAergic system, while its antidepressant effect depends upon its interaction with the serotoninergic, noradrenergic (α1 receptors), and dopaminergic (D2 dopamine receptors) systems.

  3. From pathophysiology to novel antidepressant drugs: glial contributions to the pathology and treatment of mood disorders.

    Science.gov (United States)

    Sanacora, Gerard; Banasr, Mounira

    2013-06-15

    Several structural and cellular changes, including marked glial anomalies, have been observed in association with major depressive disorder. Here we review these cellular alterations and highlight the importance of glial cell pathology, especially astroglial dysfunction, in the pathophysiology of neuropsychiatric disorders with a particular interest in major depressive disorder. The functional role of astrocytes in glutamate uptake and glutamate/glutamine cycling is discussed, as is the deleterious effects of chronic stress on glial cell function. Lastly, we discuss the effect of antidepressants on glial cell function and the possibility of targeting glial cells in the quest to develop novel therapeutics. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.

    Directory of Open Access Journals (Sweden)

    Milan Scheidegger

    Full Text Available Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI, the "dorsal nexus "(DN was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN, the default mode network (DMN, and a rostral affective network (AN. Hence, Sheline and colleagues (2010 proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC and medioprefrontal cortex (MPFC via its representative hub, the posterior cingulate cortex (PCC. These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.

  5. [Antidepressants in bipolar disorder].

    Science.gov (United States)

    Courtet, P; Samalin, L; Olié, E

    2011-12-01

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

  6. Detection of basic drugs (methamphetamine, antidepressants, and nicotine) from human hair.

    Science.gov (United States)

    Ishiyama, I; Nagai, T; Toshida, S

    1983-04-01

    Human hair contains methamphetamine, amitriptyline, imipramine, nicotine, and their metabolites in some amount, which can be detected by routine toxicological methods. Sometimes, the level of drugs reaches over 100 micrograms/g. Animal experiments indicate that these drugs are found solely in sections of hair grown after administration of the drugs. The negative stage after the administration of drugs means that the hair section containing drugs has not come out of the hair follicle. Toxicological examination of the hairs may give some clue helping to identify the chronology of the intoxication.

  7. The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs

    OpenAIRE

    Chouinard, Guy

    2006-01-01

    Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, ...

  8. Sertraline: a new antidepressant.

    Science.gov (United States)

    Auster, R

    1993-08-01

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

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

    Science.gov (United States)

    Nutt, David J

    2006-01-01

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

  10. Escitalopram versus other antidepressive agents for depression

    Science.gov (United States)

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

    2014-01-01

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

  11. Active metabolites as antidepressant drugs: The role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders

    Directory of Open Access Journals (Sweden)

    Francisco eLopez-Munoz

    2013-09-01

    Full Text Available Active metabolites of some antipsychotic drugs exhibit pharmacodynamic and pharmacokinetic properties that may be similar to or differ from the original compound and that can be translated by a different profile of responses and interactions to clinical level. Some of these antipsychotics’ active metabolites might participate in mechanisms of antidepressant activity, as m-chlorophenylpiperazine (aripiprazole, 9-OH-risperidone and norquetiapine. Norquetiapine exhibits distinct pharmacological activity from quetiapine and plays a fundamental role in its antidepressant efficacy. In this review, we analyze the differential pharmacological aspects between quetiapine and norquetiapine, both from the pharmacokinetic and pharmacodynamic perspectives (affinity for dopaminergic, noradrenegic and/or serotonergic receptors, etc., as well as differential neuroprotective role. The pharmacological differences between the two drugs could explain the differential clinical effect, as well as some differences in tolerability profile and drug interactions. The available data are sufficient to arrive at the conclusion that antidepressant activity of quetiapine is mediated, at least in part, by the active metabolite norquetiapine, which selectively inhibits noradrenaline reuptake, is a partial 5-HT1A receptor agonist, and acts as an antagonist at presynaptic α2, 5-HT2C and 5-HT7 receptors.

  12. (/sup 3/H)adrenaline release from hypothalamic synaptosomes and its modulation by clonidine: effects of chronic antidepressant drug regimens

    Energy Technology Data Exchange (ETDEWEB)

    McWilliam, J.R.; Campbell, I.C.

    1987-07-13

    (/sup 3/H)Adrenaline ((/sup 3/H)ADR, 40nM) was accumulated by rat hypothalamic synaptosomes (P/sub 2/) more rapidly and in significantly greater amounts than by similar preparations from cerebral cortex. There was no significant difference between these two tissues in the rate or amount of (/sup 3/H)noradrenaline ((/sup 3/H)NA, 40nM) accumulation. Talusupram (10..mu..M), maximally inhibited the uptake of (/sup 3/H)ADR into hypothalamic synaptosomes by 60%. Nomifensine further inhibited uptake by 14%. From these observations it was concluded that some (/sup 3/H)ADR was accumulated into non adrenergic neuronal terminals. The effects of desipramine (DMI, 10mg/kg/day and clorgyline (1mg/kg/day) administration for 28 days on K/sup +/-evoked release of (/sup 3/H)ADR was investigated using superfused hypothalamic synaptosomes. After both chronic antidepressant drug regimens, total (/sup 3/H)ADR release (spontaneous + evoked) was significantly reduced. Evoked release of (numberH)ADR (by KCl, 16mM) was significantly reduced after the DMI but not the clorgyline regimens. Presynaptic ..cap alpha../sub 2/-adrenoceptor function in the hypothalamus was assessed during superfusion by measuring the reduction in /sup +/-evoked release of (/sup 3/H)ADR caused by clonidine (1/sup +/M). 30 references, 3 figures, 1 table.

  13. [3H]adrenaline release from hypothalamic synaptosomes and its modulation by clonidine: effects of chronic antidepressant drug regimens

    International Nuclear Information System (INIS)

    McWilliam, J.R.; Campbell, I.C.

    1987-01-01

    [ 3 H]Adrenaline ([ 3 H]ADR, 40nM) was accumulated by rat hypothalamic synaptosomes (P 2 ) more rapidly and in significantly greater amounts than by similar preparations from cerebral cortex. There was no significant difference between these two tissues in the rate or amount of [ 3 H]noradrenaline ([ 3 H]NA, 40nM) accumulation. Talusupram (10μM), maximally inhibited the uptake of [ 3 H]ADR into hypothalamic synaptosomes by 60%. Nomifensine further inhibited uptake by 14%. From these observations it was concluded that some [ 3 H]ADR was accumulated into non adrenergic neuronal terminals. The effects of desipramine (DMI, 10mg/kg/day and clorgyline (1mg/kg/day) administration for 28 days on K + -evoked release of [ 3 H]ADR was investigated using superfused hypothalamic synaptosomes. After both chronic antidepressant drug regimens, total [ 3 H]ADR release (spontaneous + evoked) was significantly reduced. Evoked release of [numberH]ADR (by KCl, 16mM) was significantly reduced after the DMI but not the clorgyline regimens. Presynaptic α 2 -adrenoceptor function in the hypothalamus was assessed during superfusion by measuring the reduction in + -evoked release of [ 3 H]ADR caused by clonidine (1 + M). 30 references, 3 figures, 1 table

  14. The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs.

    Science.gov (United States)

    Chouinard, Guy

    2006-05-01

    Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, such as in panic disorder and mania, were found with the introduction of 2 high-potency benzodiazepines, clonazepam and alprazolam, which were thought to have serotonergic properties. Our initial clinical trials of fluoxetine and sertraline led to their approved indications in the treatment of obsessive-compulsive disorder, and our trials of gabapentin led to new indications in anxiety disorders (generalized anxiety, panic attack and social phobia) and sleep disorders (insomnia).

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

    African Journals Online (AJOL)

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

  16. Genotoxic effect of the tricyclic antidepressant drug clomipramine hydrochloride in somatic and germ cells of male mice

    Directory of Open Access Journals (Sweden)

    Samia Ahmed El-Fiky

    2016-04-01

    Full Text Available Objective: To assess the genotoxic potential of the antidepressant drug clomipramine hydrochloride (CH through different mutagenic end points. Methods: The study included chromosomal aberration analysis of bone marrow cells, primary spermatocytes, morphological sperm abnormalities and histopathological changes of liver cells using both light and electron microscopy. Three doses (0.195, 0.26 and 0.65 mg/20 g body weight were tested. Each dose was given orally to mice for different periods of time (the doses are equivalent to the recommended daily intake doses in man. Results: The tested doses of CH applied for 5 and 30 days increased the frequencies of chromosomal aberrations with dose and time dependant manner. The two high doses, 0.26 and 0.65 mg/20 g body weight revealed significant effect in comparison to the control. Dose -dependent increase in morphological sperm abnormalities and decrease in sperm count were recorded after CH treatment for 5 consecutive days. Pathological changes in liver tissue reached to sever damage were recorded after treatment with the medium and the high doses for 30 days. Ultrastructural examination showed that the low dose had little differences in liver histological architecture as compared to the control group, while prominent pathological changes in nuclei as well as dilated rough endoplasmic reticulum were observed in mice treated with the medium or the high dose of the drug. Conclusions: It is concluded that CH has genotoxic effect in somatic and germ cells of mice as well as damaging effect on liver tissue after treatment with the medium and the high doses. However, the usage of low dose (especially for short time, 5 days can be utilized as a safe therapeutic dose.

  17. A Fluorescence Displacement Assay for Antidepressant Drug Discovery Based on Ligand-Conjugated Quantum Dots

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jerry [Vanderbilt University; Tomlinson, Ian [Oak Ridge National Laboratory (ORNL); Warnement, Michael [Vanderbilt University; Iwamoto, Hideki [Vanderbilt University

    2011-01-01

    The serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) protein plays a central role in terminating 5-HT neurotransmission and is the most important therapeutic target for the treatment of major depression and anxiety disorders. We report an innovative, versatile, and target-selective quantum dot (QD) labeling approach for SERT in single Xenopus oocytes that can be adopted as a drug-screening platform. Our labeling approach employs a custom-made, QD-tagged indoleamine derivative ligand, IDT318, that is structurally similar to 5-HT and accesses the primary binding site with enhanced human SERT selectivity. Incubating QD-labeled oocytes with paroxetine (Paxil), a high-affinity SERT-specific inhibitor, showed a concentration- and time-dependent decrease in QD fluorescence, demonstrating the utility of our approach for the identification of SERT modulators. Furthermore, with the development of ligands aimed at other pharmacologically relevant targets, our approach may potentially form the basis for a multitarget drug discovery platform.

  18. Amphetamine and antidepressant drug effects on GABA- and NMDA-related seizures.

    Science.gov (United States)

    Borowski, T B; Kirkby, R D; Kokkinidis, L

    1993-01-01

    Research has shown a synergistic relationship between amphetamine sensitization and limbic system kindling. To explore the role of GABA and NMDA receptor activity in modulating the positive effects of amphetamine on epileptogenesis, alterations in GABA- and NMDA-related convulsions were examined after acute and chronic amphetamine administration. A single injection of d-amphetamine (7.5 mg/kg) significantly decreased latencies to generalized motor seizures induced 12 h later by the noncompetitive GABAA receptor antagonist picrotoxin (10 mg/kg). The increased sensitivity to clonus was specific to acute amphetamine treatment and was not evident following withdrawal from chronic drug exposure. Seizures induced by NMDLA (1,000 mg/kg), on the other hand, were not modified by acute amphetamine injection; however, the latency to clonus was reduced substantially after NMDLA injection to mice chronically preexposed to amphetamine. The short- and long-term amphetamine effects on GABA- and NMDA-associated convulsive activity were not paralleled by similar drug treatment schedules involving acute (20 mg/kg) and chronic administration of desipramine, zimelidine, and buproprion. These results suggest that amphetamine may be acting on inhibitory and excitatory amino acid systems independently of its monoaminergic properties. The implications of these findings were discussed in relation to amphetamine sensitization of mesolimbic functioning.

  19. Iatrogenic Cushing’s syndrome with inhaled steroid plus antidepressant drugs

    Science.gov (United States)

    2012-01-01

    Current guidelines recommend the use of inhaled corticosteroids (ICS) for suppression of airway inflammation in patients with asthma. Although it is well known that ICS cause dose-related adrenocortical suppression, it is less known that they can lead to iatrogenic Cushing’s syndrome (CS). Fluticasone propionate (FP) is an ICS more potent than beclomethasone and budesonide. FP is metabolized as mediated by cytochrome P450 3A4 in the liver and the gut. Systemic bioactivity of FP can increase with the use of drugs that affect the cytochrome P450. Herein, we report the rapid development of iatrogenic CS in a patient receiving paroxetine and mirtazepine for 12 weeks in addition to inhaled FP. PMID:22958272

  20. Antidepressant Withdrawal

    Science.gov (United States)

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

  1. 125I-labelled iodothyronines. Useful tools for studies of effects of an antidepressant drug fluoxetine in the rat

    International Nuclear Information System (INIS)

    Stanislav Pavelka; Masaryk University, Brno

    2010-01-01

    Thyroid hormones (TH) are supposed to control the activity of some neurotransmitters (e.g., serotonin), which are hypothetically involved in the pathogenesis of depressive illness. A new group of non-tricyclic antidepressant drugs includes selective serotonine re-uptake inhibitors. The most frequently used representative of this group is fluoxetine (Fluox). We followed in the present paper the effects of Fluox, administered subchronicaly (for 25 days) to Wistar rats by itself, or in combination with 3,3',5-triiodo-l-thyronine (T 3 ). In studies of the interaction of Fluox with the metabolism of TH, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT), as well as our newly developed radiometric assays for iodothyronine deiodinases (IDs) of types 1, 2 and 3 (D1, D2 and D3), using 125 I-labelled iodothyronines of high specific radioactivity as substrates. We found about two-fold higher UDP-GT enzyme activities in samples of liver microsomes of rats treated with Fluox, in comparison with control rats. In contrast, the radiometric determination of ST activities in liver and kidney cytosolic fractions did not demonstrate any significant effects of the administration of Fluox, alone or together with T 3 , on the induction of these enzymes. However, profound changes in enzyme activities were determined in case of IDs, especially in the pituitary and cerebellum of treated rats. The adapted and newly elaborated radiometric enzyme assays proved to be very sensitive and rapid and, at the same time, reliable and robust. (author)

  2. A comparison of cognitive-behavioral therapy, antidepressants, their combination and standard treatment for Chinese patients with moderate-severe major depressive disorders.

    Science.gov (United States)

    Zu, Si; Xiang, Yu-Tao; Liu, Jing; Zhang, Ling; Wang, Gang; Ma, Xin; Kilbourne, Amy M; Ungvari, Gabor S; Chiu, Helen F K; Lai, Kelly Y C; Wong, Samuel Y S; Yu, Doris S F; Li, Zhan-Jiang

    2014-01-01

    No study has examined the effect of cognitive-behavioral therapy (CBT) on moderate-severe major depressive disorders (MDD) in China. The objective of this study was to evaluate the effect of CBT, antidepressants alone (MED), combined CBT and antidepressants (COMB) and standard treatment (ST; i.e., receiving psycho-educational intervention and/or medication treatment determined by treating psychiatrists) on depressive symptoms and social functioning in Chinese patients with moderate-severe MDD. A total of 180 patients diagnosed with MDD according to ICD-10 were randomly allocated to one of the four treatment regimens for a period of 6 months. Depressive symptoms were measured using the Hamilton Rating Scale for Depression (HAMD) and the Quick Inventory of Depressive Symptomatology-Self-Report (C-QIDS-SR). Remission threshold was defined as a C-QIDS-SR total score of combined CBT-antidepressant treatment in controlling the remission. The study provided important knowledge to inform the mental health care planning in China. © 2013 Elsevier B.V. All rights reserved.

  3. [Multimodal serotonergic antidepressants].

    Science.gov (United States)

    Danilov, D S

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

  4. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.

    Directory of Open Access Journals (Sweden)

    Jean Mazella

    2010-04-01

    Full Text Available Current antidepressant treatments are inadequate for many individuals, and when they are effective, they require several weeks of administration before a therapeutic effect can be observed. Improving the treatment of depression is challenging. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. In mice, deletion of the TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate in mice the antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the neurotensin receptor 3 (NTSR3/Sortilin and acting through TREK-1 inhibition. NTSR3/Sortilin interacted with the TREK-1 channel, as shown by immunoprecipitation of TREK-1 and NTSR3/Sortilin from COS-7 cells and cortical neurons co-expressing both proteins. TREK-1 and NTSR3/Sortilin were colocalized in mouse cortical neurons. Spadin bound specifically to TREK-1 with an affinity of 10 nM. Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices. Spadin also induced in vivo an increase of the 5-HT neuron firing rate in the Dorsal Raphe Nucleus. In five behavioral tests predicting an antidepressant response, spadin-treated mice showed a resistance to depression as found in TREK-1 deficient mice. More importantly, an intravenous 4-d treatment with spadin not only induced a strong antidepressant effect but also enhanced hippocampal phosphorylation of CREB protein and neurogenesis, considered to be key markers of antidepressant action after chronic treatment with selective serotonin reuptake inhibitors. This work also shows the development of a reliable method for dosing the propeptide in serum of mice by using AlphaScreen technology. These findings point out

  5. Ionic liquid based dispersive liquid-liquid microextraction coupled with micro-solid phase extraction of antidepressant drugs from environmental water samples.

    Science.gov (United States)

    Ge, Dandan; Lee, Hian Kee

    2013-11-22

    Ionic liquid-dispersive liquid-liquid microextraction combined with micro-solid phase extraction (IL-DLLME-μ-SPE), and high-performance liquid chromatography (HPLC) was developed for the determination of tricyclic antidepressants (TCAs) in water samples. Two hundred microliters of an organic solvent (as disperser solvent) and 20 μl of 1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate were injected into a 5.0 ml sample for sonication-assisted DLLME. After this, a μ-SPE device, containing a novel material zeolite imidazolate framework 4 (ZIF-4), was added into the sample solution and 1 min of vortex-assisted extraction was performed. After 5 min of sonication-assisted desorption, 10 μl of desorption solvent was injected into a HPLC system for analysis. A characteristic property of DLLME-VA-μ-SPE is that any organic solvent and solid sorbent immiscible with water can be used. Special apparatus, or conical-bottom test tubes, and tedious procedures conventionally associated with DLLME such as centrifugation, or refrigeration of solvent are not necessary in the present approach. A novel material, ZIF-4 was employed as μ-SPE sorbent. Under the optimized conditions, the calibration curves were linear in the range of 1-1000 μg/L. The relative standard deviations and the limits of detection were in the range of 1.5% and 7.8% and 0.3 and 1 μg/L, respectively. The relative recoveries of canal water samples, spiked with drugs, were in the range of 94.3% and 114.7%. The results showed that IL-DLLME-μ-SPE was suitable for the determination of TCAs in water samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Tricyclic Antidepressants and Tetracyclic Antidepressants

    Science.gov (United States)

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

  7. Nanomaterials potentiating standard chemotherapy drugs' effect

    Science.gov (United States)

    Kazantsev, S. O.; Korovin, M. S.

    2017-09-01

    Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

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

    Science.gov (United States)

    Hughes, Shannon; Cohen, David; Jaggi, Rachel

    2014-07-09

    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. 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. Clinicalstudyresults.org, sponsored by Pharmaceutical Research and Manufacturers of America; clinicaltrials.gov, administered by the US National Institutes of Health. 3 coders extracted data on the numbers and types of SAEs. 244 trial summaries for six antidepressant and antipsychotic drugs were retrieved, 142 (58.2%) listing an associated article. Of 1608 SAEs in drug-treated participants according to trial summaries, 694 (43.2%) did not appear in associated articles. Nearly 60% of SAEs counted in articles and 41% in trial summaries had no description. Most cases of death (62.3%) and suicide (53.3%) were not reported in articles. Half or more of the 142 pairs were discordant in reporting the number (49.3%) or description (67.6%) of SAEs. These discrepancies resulted from journal articles' (1) omission of complete SAE data, (2) reporting acute phase study results only and (3) more restrictive reporting criteria. Trial summaries with zero SAE were 2.35 (95% CI, 1.58 to 3.49; pjournal article. Since clinicalstudyresults.org was removed from the Internet in 2011, only 7.8% of retrieved trial summaries appear with results on clinicaltrials.gov. Substantial discrepancies exist in SAE data found in journal articles and registered summaries of antidepressant and antipsychotic drug trials. Two main scientific sources accessible to clinicians and researchers are limited by incomplete, ambiguous and inconsistent reporting. Access to complete and accurate data from clinical trials of drugs currently in use remains a pressing concern. Published by the BMJ Publishing Group Limited

  9. Antidepressants and Weight Gain

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  11. Effects of Antidepressants on Sleep.

    Science.gov (United States)

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

    2017-08-09

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  13. Treatment with antidepressants and lithium is associated with increased risk of treatment with antiparkinson drugs: a pharmacoepidemiological study

    DEFF Research Database (Denmark)

    Brandt-Christensen, Anne Mette; Kvist, Tine Kajsa; Nielsen, F.M.

    2006-01-01

    .42) for men and 1.50 (95% CI 1.43 to 1.58) for women. Figures for lithium were almost identical. CONCLUSION: Persons treated with antidepressants or lithium are at increased risk of subsequently treatment with APD, showing an association between anxiety/affective disorder and Parkinson's disease....

  14. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

    Directory of Open Access Journals (Sweden)

    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  15. Antidepressant-induced liver injury.

    Science.gov (United States)

    DeSanty, Kevin P; Amabile, Celene M

    2007-07-01

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

  16. Switching antidepressants

    African Journals Online (AJOL)

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

  17. 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.

  18. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis.

    Science.gov (United States)

    Sidor, Michelle M; Macqueen, Glenda M

    2011-02-01

    The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression. EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles. Trials that compared acute (antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch. Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants. Although antidepressants were

  19. 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.

  20. Tricyclic antidepressant radioreceptor assay

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  1. Adverse reactions to antidepressants

    DEFF Research Database (Denmark)

    Uher, Rudolf; Farmer, Anne; Henigsberg, Neven

    2009-01-01

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

  2. Diving and antidepressants.

    Science.gov (United States)

    Querido, Abraham L

    2017-12-01

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

  3. Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action

    DEFF Research Database (Denmark)

    Cerit, Hilâl; Veer, Ilya M; Dahan, Albert

    2015-01-01

    faces in the fusiform gyrus. ARA290 tended to lower the recognition of happy and disgust facial expressions. Although ARA290 was not associated with a better memory for positive words, it was associated with faster categorization of positive vs negative words. Finally, ARA290 increased attention towards...... positive emotional pictures. No effects were observed on mood and affective symptoms. ARA290 may modulate some aspects of emotional processing, however, the direction and the strength of its effects do not unequivocally support an antidepressant-like profile for ARA290. Future studies may investigate...

  4. Should patients with schizophrenia receive antidepressants?

    Science.gov (United States)

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

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

  5. 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

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

    NARCIS (Netherlands)

    R. Noordam (Raymond)

    2015-01-01

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

  7. Antidepressant prescribing in five European countries: application of common methods to assess the variation in prevalence.

    NARCIS (Netherlands)

    Abbing-Karahagopian, V.; Huerta, C.; Souverein, P.C.; Abajo, F. de; Leufkens, H.G.M.; Slattery, J.; Alvarez, Y.; Montserrat, M.; Gill, M.; Hesse, U.; Requena, G.; Vries, F. de; Rottenkolber, M.; Schmiedl, S.; Reynolds, R.; Schlinger, R.; Groot, M. de; Klungel, O.H.; Staa, T.P. van; Dijk, L. van; Egberts, A.C.G.; Gardarsdottir, H.; Bruin, M.L. de

    2013-01-01

    Background: Drug utilization studies have applied different methods on various data types to describe medication use which may hamper comparisons across populations. Objectives: The aim of this study was to describe the variation in the prevalence of antidepressant prescribing, applying standard

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    OBJECTIVE: Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers....... The current study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients. METHOD: Nineteen acutely depressed patients were randomized to receive Epo (40,000 IU) or saline intravenously in a double-blind, parallel-group design. On day 3, we...... assessed neuronal responses to fearful and happy faces using functional magnetic resonance imaging and measured facial expression recognition after the scan. RESULTS: Epo reduced neural response to fearful vs. happy faces in the amygdala and hippocampus, and to fearful faces vs. baseline in superior...

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

    Science.gov (United States)

    Farahani, Arusha; Correll, Christoph U

    2012-04-01

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

  10. [Antidepressive agents and breast feeding].

    Science.gov (United States)

    Håberg, M; Matheson, I

    1997-11-10

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

  11. Pharmacognostic standardization of Homoeopathic drug: Juniperus virginiana L.

    Directory of Open Access Journals (Sweden)

    P Padma Rao

    2015-01-01

    Full Text Available Background: Juniperus virginiana L., commonly known as ′red cedar′ in English is a well-known evergreen tree belonging to the family Cupressaceae. The leaves and young aerial shoots are used for preparation of medicine in Homoeopathy. Objective: Standardization is the quintessential aspect which ensures purity and quality of drugs. Hence, the pharmacognostic and physico-chemical studies are carried out to facilitate the use of authentic and correct species of raw drug plant material with established parametric standards for manufacturing the drug. Materials and Methods: Pharmacognostic studies on leaves and young aerial parts of authentic samples of J. virginiana L. have been carried out; physico-chemical parameters of raw drug viz., extractive values, ash values, formulation, besides weight per mL, total solids, alcohol content along with High Performance Thin Layer Chromatography (HPTLC and ultraviolet visible studies have been worked out for mother tincture. Results: The leaves are needles, narrow and sharp at tips; stems are round with greyish white to brown bark possessing small lenticels and covered by imbricate leaves. Epidermal cells in the surface have polygonal linear sides with pitted walls containing crystals and starch. Stomata exclusively occur on the adaxial surface in linear rows. Hypodermis of leaf in T.S. is marked with 1-2 layered lignified sclerenchyma. 2-4 secretory canals are present with one conspicuously beneath midvein bundle. The young terminal axis is sheathed by two closely surrounding leaves while the mature stem possess four leaf bases attached. Vascular tissue of stem possesses predominant xylem surrounded by phloem containing sphaeraphides, prismatic crystals and starch grains. Uniseriate rays occur in the xylem. Mature stem possess shrivelled cork, followed by the cortex. Physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and

  12. Antidepressant prescribing in five European countries

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  13. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

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

  14. Volumetric and ultrasonic studies of an antidepressant drug in aqueous and alcoholic medium over temperature range 298.15-313.15 k

    International Nuclear Information System (INIS)

    Jamal, M.A.; Khosa, M.K.; Muneer, M.; Shahzad, K.

    2013-01-01

    Escitalopram oxalate is an amphiphilic serotonin specific reuptake inhibitor-antidepressant drug. Ultrasonic velocity (u) and density (d) measurements were carried out for Escitalopram oxalate in aqueous and alcoholic systems as a function of concentration in a range of molality, m (0.0075-0.04) mol Kg-1 at 298.15-313.15 K using an Anton Paar density sound analyzer (DSA 5000M). Using these experimental values, the acoustical parameters such as apparent molar adiabatic compressibility and partial molar volume (V phi) was apparent molar volume (V phi (K computed for all the systems. The Partial molar expansivity (E/sup 0/) and second derivative values, (partial drive V/sup 0/partial drive T/sup 2/), have also been estimated. The critical micelle concentrations of this drug were obtained from ultrasound velocity measurement by using recently developed least square fitting algorithm. The results are interpreted in the light of structure-making or structure-breaking effects of escitalopram oxalate in the mixtures. (author)

  15. Pharmacognostic and physicochemical standardization of homoeopathic drug: Rumex crispus L.

    Directory of Open Access Journals (Sweden)

    Subramanian Palani

    2016-01-01

    Full Text Available Background: Rumex crispus L., commonly called as "yellow dock" in English, "patience frisee" in French, and "Ampfer" in German, and ′aceda de culebra′ in Spanish is a well-known herb belonging to Polygonaceae. Roots of the herb are used as medicine in homoeopathy. Objective: The pharmacognostic and physicochemical studies on roots have been carried out to enable the use of correct species and standardize the raw material. Materials and Methods: Pharmacognostic studies on roots of authentic raw drug have been carried out; physicochemical parameters, namely, extractive value, ash values, formulation besides weight per mL, total solids, alcohol content along with high-performance thin layer chromatography (HPTLC and ultraviolet studies for mother tincture have been worked out. Results: Roots are blackish-brown, wiry, rounded with irregular striations, tortuous; internally, it is softwood, light-yellow, and fracture fibrous. Phellem is 8-10 layered, discontinuous, and tanniniferous. Phellogen is two-layered and contains inulin crystals in few. Outer phelloderm is 12-16 layered often containing spherocrystals and associated with stone cells. Secondary phloem is up to 25 layered. Xylem is in the form of strips. The physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and organoleptic characters along with anatomical and physicochemical studies are diagnostic to establish standards for the drug.

  16. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

    International Nuclear Information System (INIS)

    2016-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  17. [Interactions between metoprolol and antidepressants].

    Science.gov (United States)

    Molden, Espen; Spigset, Olav

    2011-09-20

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

  18. 49 CFR 219.701 - Standards for drug and alcohol testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

  19. Degradation of antidepressant drug fluoxetine in aqueous media by ozone/H2O2 system: process optimization using central composite design.

    Science.gov (United States)

    Aghaeinejad-Meybodi, Abbas; Ebadi, Amanollah; Shafiei, Sirous; Khataee, Alireza; Rostampour, Mohammad

    2015-01-01

    The main objective of this work is the modelling and optimization of antidepressant drug fluoxetine degradation in aqueous solution by ozone/H2O2 process using central composite design. The operational parameters were ozone concentration, initial hydrogen peroxide concentration, reaction time and initial fluoxetine concentration. A good agreement between the predicted values of fluoxetine removal and experimental results were observed (R2=0.976 and Adj-R2=0.955). Pareto analysis indicated that all selected factors and some interactions were effective on the removal efficiency. It was found that the reaction time is the most effective parameter in the ozone/H2O2 process. The maximum removal efficiency (86.14%) was achieved at ozone concentration of 30 mg L(-1), initial H2O2 concentration of 0.02 mM, reaction time of 20 min and initial fluoxetine concentration of 50 mg L(-1) as the optimum conditions.

  20. Antidepressants and Alcohol

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

    Korf, J

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

  2. 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

  3. Antidepressant-selective gynecomastia.

    Science.gov (United States)

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

    2013-01-01

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

  4. Safety of antidepressants

    NARCIS (Netherlands)

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

    1995-01-01

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

  5. 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

  6. Influence of antidepressants on hemostasis

    Science.gov (United States)

    Halperin, Demian; Reber, Guido

    2007-01-01

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

  7. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos. FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and Innovation Act Title VII--Drug Supply Chain; Standards for Admission of Imported Drugs, Registration of...

  8. Serotonergic antidepressants as predictors of depressive disorders treatment

    Directory of Open Access Journals (Sweden)

    Timotijević Ivana P.

    2014-01-01

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

  9. [Antidepressants in the elderly].

    Science.gov (United States)

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

    2016-10-01

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

  10. Antidepressants and dementia

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  11. Antidepressants and dementia

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Evaluation of the binding of the radiolabeled antidepressant drug, {sup 18}F-fluoxetine in the rodent brain: an in vitro and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, Jogeshwar E-mail: jogeshwar_mukherjee@ketthealth.com; Das, Malay K.; Yang Zhiying; Lew, Robert

    1998-10-01

    We have developed {sup 18}F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of {sup 18}F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of {sup 18}F-fluoxetine was not obtained. Even when fluoxetine (10 {mu}M) was used for measurements of nonspecific binding, a saturation curve was difficult to obtain. Other compounds, such as deprenyl, clorgyline, amphetamine, and reserpine were also not able to reduce the binding of {sup 18}F-fluoxetine. Ex vivo autoradiographic experiments with {sup 18}F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of {sup 18}F-fluoxetine in rats showed similar uptake in all the brain regions with little regional selectivity. A subcellular analysis of rat brain tissue after intravenous (IV) administration of {sup 18}F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with {sup 18}F-fluoxetine indicate little specific binding. Binding to the serotonin transporter was not identifiable. High nonspecific binding of the tracer resulting from its subcellular nature in the brain masks the ability to detect binding to the serotonin uptake sites in vivo. These findings indicate that a large portion of the binding of {sup 18}F-fluoxetine in rat brains is subcellular and clears slowly out of the cells. Other sites, such as monoamine oxidase, may also play a significant role in the action of fluoxetine.

  14. The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

    Directory of Open Access Journals (Sweden)

    Patrick A Randall

    Full Text Available Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2 inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA. Rats were assessed using a concurrent progressive ratio (PROG/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1 and eticlopride (D2, but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a

  15. Evaluation of the binding of the radiolabeled antidepressant drug, 18F-fluoxetine in the rodent brain: an in vitro and in vivo study

    International Nuclear Information System (INIS)

    Mukherjee, Jogeshwar; Das, Malay K.; Yang Zhiying; Lew, Robert

    1998-01-01

    We have developed 18 F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of 18 F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of 18 F-fluoxetine was not obtained. Even when fluoxetine (10 μM) was used for measurements of nonspecific binding, a saturation curve was difficult to obtain. Other compounds, such as deprenyl, clorgyline, amphetamine, and reserpine were also not able to reduce the binding of 18 F-fluoxetine. Ex vivo autoradiographic experiments with 18 F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of 18 F-fluoxetine in rats showed similar uptake in all the brain regions with little regional selectivity. A subcellular analysis of rat brain tissue after intravenous (IV) administration of 18 F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with 18 F-fluoxetine indicate little specific binding. Binding to the serotonin transporter was not identifiable. High nonspecific binding of the tracer resulting from its subcellular nature in the brain masks the ability to detect binding to the serotonin uptake sites in vivo. These findings indicate that a large portion of the binding of 18 F-fluoxetine in rat brains is subcellular and clears slowly out of the cells. Other sites, such as monoamine oxidase, may also play a significant role in the action of fluoxetine

  16. Controlled release formulation of an anti-depression drug based on a L-phenylalanate-zinc layered hydroxide intercalation compound

    Science.gov (United States)

    Hashim, Norhayati; Sharif, Sharifah Norain Mohd; Isa, Illyas Md; Hamid, Shahidah Abdul; Hussein, Mohd Zobir; Bakar, Suriani Abu; Mamat, Mazidah

    2017-06-01

    The intercalation of L-phenylalanate (LP) into the interlayer gallery of zinc layered hydroxide (ZLH) has been successfully executed using a simple direct reaction method. The synthesised intercalation compound, zinc layered hydroxide-L-phenylalanate (ZLH-LP), was characterised using PXRD, FTIR, CHNS, ICP-OES, TGA/DTG, FESEM and TEM. The PXRD patterns of the intercalation compound demonstrate an intense and symmetrical peak, indicating a well-ordered crystalline layered structure. The appearance of an intercalation peak at a low angle of 2θ with a basal spacing of 16.3 Å, signifies the successful intercalation of the L-phenylalanate anion into the interlayer gallery of the host. The intercalation is also validated by FTIR spectroscopy and CHNS elemental analysis. Thermogravimetric analysis confirms that the ZLH-LP intercalation compound has higher thermal stability than the pristine L-phenylalanine. The observed percentage of L-phenylalanate accumulated release varies in each release media, with 84.5%, 79.8%, 63.8% and 61.8% release in phosphate buffer saline (PBS) solution at pH 4.8, deionised water, PBS solution at pH 7.4 and NaCl solution, respectively. The release behaviour of LP from its intercalation compounds in deionised water and PBS solution at pH 4.8 follows pseudo second order, whereas in NaCl solution and PBS solution at pH 7.4, it follows the parabolic diffusion model. This study shows that the synthesised ZLH-LP intercalation compound can be used for the formation of a new generation of materials for targeted drug release with controlled release properties.

  17. New generation of antidepressants in pregnant women

    Directory of Open Access Journals (Sweden)

    Ladan Kashani

    2007-03-01

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

  18. Chirality of Modern Antidepressants: An Overview

    Directory of Open Access Journals (Sweden)

    Monica Budău

    2017-12-01

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

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. 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

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

    Science.gov (United States)

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

    2016-10-01

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

  4. Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies.

    Science.gov (United States)

    Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Rive, Benoît; Salah, Samir; Ereshefsky, Larry; Francois, Clément

    2014-12-01

    Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012). We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events). For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio antidepressant effect estimates or relative ranking. These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity). Key messages: Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to

  5. Antidepressants during pregnancy, risks for mother and child

    NARCIS (Netherlands)

    Ververs, F.F.T.

    2009-01-01

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

  6. 75 FR 34452 - Center for Drug Evaluation and Research Data Standards Plan; Availability for Comment

    Science.gov (United States)

    2010-06-17

    ... HUMAN SERVICES Food and Drug Administration Center for Drug Evaluation and Research Data Standards Plan... development of a comprehensive data standards program in the Center for Drug Evaluation and Research (CDER... Administration (FDA) is announcing the availability for public comment of the draft document entitled ``CDER Data...

  7. Detecção de risco de interações entre fármacos antidepressivos e associados prescritos a pacientes adultos Interaction risk detection between antidepressant and associated drugs prescribed for adult patients

    Directory of Open Access Journals (Sweden)

    Kassia Fernanda Campigotto

    2008-01-01

    Full Text Available CONTEXTO: O uso de fármacos combinados para o tratamento de patologias diversas em psiquiatria tem aumentado progressivamente. Os antidepressivos estão envolvidos em diversas interações farmacológicas clinicamente importantes. OBJETIVO: Detectar risco de interações entre fármacos antidepressivos e associados prescritos a pacientes adultos. MÉTODOS: Pesquisa retrospectiva e descritiva foi desenvolvida em uma farmácia magistral da cidade de Cascavel, Paraná. Os dados foram coletados de 151 receituários médicos de pacientes adultos (19 anos ou mais, envolvendo fármacos antidepressivos e associados entre outubro e novembro de 2005. O estudo limitou-se às variáveis registradas no receituário médico (sexo, idade, fármaco antidepressivo e associado prescrito. RESULTADOS: A categoria de 31 a 40 anos de idade foi a mais freqüente (32,46% e o sexo foi o feminino (64,90%. Os fármacos antidepressivos tricíclicos (ADT e associados apresentaram um total de oito episódios de interações relativos ao grau de severidade, sendo quatro de grau moderado e quatro menor. Em relação aos fármacos antidepressivos inibidores seletivos da recaptura de serotonina (ISRS e associados, o risco de ocorrência foi de 16 casos; quatro de severidade menor, dez moderada e dois maior. CONCLUSÃO: Os dados mostram que os pacientes com prescrição de fármacos ISRS e associados possuíam mais risco de interações de maior severidade, totalizando o dobro de interações em relação aos ADTs.BACKGROUND: The combination of drugs for the treatment of psychiatric disorders has become a relatively frequent practice. The antidepressants are involved in several clinically important pharmacological interactions. OBJECTIVES: To detect the risk of interactions between antidepressants and associated drugs prescribed for adults patients. METHODS: Data on 151 medical prescriptions of antidepressants and other psychiatric drugs were retrospectively assessed at a

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

    Science.gov (United States)

    Kennedy, Sidney H; Rizvi, Sakina

    2009-04-01

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

  9. Chemometrics: A new scenario in herbal drug standardization

    Directory of Open Access Journals (Sweden)

    Ankit Bansal

    2014-08-01

    Full Text Available Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency. Key words: Chemometrics, HELP, Herbal drugs, PCA, OPA

  10. Screening of antidepressant activity and estimation of quercetin from Coccinia indica using TLC densitometry.

    Science.gov (United States)

    Randhawa, Kudrat; Kumar, Deepak; Jamwal, Anupam; Kumar, Suresh

    2015-01-01

    Coccinia indica Naud (Cucurbitaceae) has been traditionally used for the treatment of depression but these claims have not been validated. The objective of this study is to investigate antidepressant activity of various extracts and fractions of C. indica aerial parts, and to estimate content of quercetin in the plant using TLC densitometry. Coccinia indica aerial parts were successively extracted using solvents in increasing order of polarity, namely n-hexane, chloroform, methanol, and water. Various extracts were evaluated for antidepressant activity at doses of 200 or 400 mg/kg, p.o., upon acute administration in mice using the forced swim test (FST). The bioactive extract was partitioned successively using solvents in increasing order of polarity, namely n-hexane, ethyl acetate, and n-butanol. All fractions were also screened for antidepressant activity at doses of 25 or 50 mg/kg, p.o., upon acute administration in mice. The methanol extract significantly reduced the duration of immobility in FST at dose of 400 mg/kg without affecting locomotor activity in open field test, thus, confirmed its antidepressant activity, which was statistically equivalent to the standard drug (imipramine, 15 mg/kg, i.p.). Ethyl acetate fraction (EAF) exhibited antidepressant activity at 50 mg/kg. Comparative TLC fingerprint studies confirmed the presence of quercetin in methanol extract and EAF. Quercetin was used as a chemical marker to standardize C. indica aerial parts using the validated TLC densitometric method, and the content of quercetin was found to be 0.00172% w/w. The present studies scientifically validated traditional claims of C. indica for antidepressant activity.

  11. 33 CFR 95.020 - Standard for under the influence of alcohol or a dangerous drug.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or a dangerous drug. 95.020 Section 95.020 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.020 Standard for under the influence of alcohol or a dangerous drug. An individual is under the influence of alcohol or a dangerous drug when: (a) The individual is operating a...

  12. Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.

    Science.gov (United States)

    Hayasaka, Yu; Purgato, Marianna; Magni, Laura R; Ogawa, Yusuke; Takeshima, Nozomi; Cipriani, Andrea; Barbui, Corrado; Leucht, Stefan; Furukawa, Toshi A

    2015-07-15

    Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method. We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d. We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin. The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants. Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  13. 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.

  14. Antidepressant treatment for postnatal depression.

    Science.gov (United States)

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

    2014-09-11

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Choppadandi

    2016-06-01

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

  17. Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Nielsen, Elsebet O; Redrobe, John P

    2009-01-01

    Smoking rates among depressed individuals is higher than among healthy subjects, and nicotine alleviates depressive symptoms. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. In mice, acute nicotine administration enhances...... the activity of antidepressants in the mouse forced swim (mFST) and tail suspension tests. Here, we investigated if this action of nicotine is also reflected in a chronic treatment regimen....

  18. ANTIDEPRESSANT THERAPY IN HIGH-RISK PATIENTS

    African Journals Online (AJOL)

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

  19. Antidepressants for depression in adults with HIV infection.

    Science.gov (United States)

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

    2018-01-22

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

  20. Use of Antidepressants

    Science.gov (United States)

    Kalali, Amir H.; Thase, Michael E.

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Majeed Azeem

    2004-12-01

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

  2. Poisoining with Tricyclic Antidepressants and Current Treatment

    Directory of Open Access Journals (Sweden)

    Muge Gulen

    2016-12-01

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

  3. 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.

  4. The effect of antidepressants on fertility.

    Science.gov (United States)

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

    2016-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Jesberger, J.A.

    1984-01-01

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

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

    Science.gov (United States)

    2012-01-01

    Background Hibiscus tiliaceus L. (Malvaceae) is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. Methods Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. Results Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. Conclusion Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect. PMID:22494845

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

    Directory of Open Access Journals (Sweden)

    Vanzella Cláudia

    2012-04-01

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

  8. Anti-depressants and suicide.

    Science.gov (United States)

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

    2009-05-01

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

  9. 21 CFR 70.10 - Color additives in standardized foods and new drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Color additives in standardized foods and new... SERVICES GENERAL COLOR ADDITIVES General Provisions § 70.10 Color additives in standardized foods and new... proposes the inclusion of a color additive in the standardized food, the provisions of the regulations in...

  10. Solid phase extraction of antidepressant drugs amitriptyline and nortriptyline from plasma samples using core-shell nanoparticles of the type Fe3O4-ZrO2-N- cetylpyridinium, and their subsequent determination by HPLC with UV detection

    International Nuclear Information System (INIS)

    Zare, Fahimeh; Ghaedi, Mehrorang; Daneshfar, Ali

    2015-01-01

    The solid phase extraction (SPE) is described for preconcentration of the antidepressant drugs amitriptyline and nortriptyline prior to their determination by HPLC with UV detection. It is based on the use of water-dispersible core-shell nanoparticles (NPs) of the Fe 3 O 4 -ZrO 2 -N-cetylpyridinium type. The positively charged surfactant N-cetylpyridinium forms mixed aggregates with the drugs on the surface of the core-shell and thereby improves the adsorption of amitriptyline and nortriptyline through hydrophobic and/or ionic interactions. Their extraction depends on the type and amount of surfactant, sample pH, extraction time, desorption conditions, sample volume and amount of NPs that were optimized by application of experimental design. The enrichment factors are 220 and 250, respectively, for amitriptyline and nortriptyline, and the detection limits are 0.04 and 0.08 ng·mL -1 . This protocol enables accurate and precise quantification of the two drugs in complex and low content samples. It was applied to the determination of the two drugs in plasma samples with relative recoveries in the range from 89 to 105 % and RSDs less than 4 %. (author)

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

    Khan, Arif; Brown, Walter A

    2015-10-01

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

  13. [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.

  14. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    Directory of Open Access Journals (Sweden)

    Javad Maleki

    2007-09-01

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

  15. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2007-08-01

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

  16. Drug Combinations as the New Standard for Melanoma Treatment.

    Science.gov (United States)

    Polkowska, Marta; Czepielewska, Edyta; Kozłowska-Wojciechowska, Małgorzata

    2016-12-01

    Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach. Targeted therapy combinations allowed a better response rate and progression-free survival than monotherapy with one of the agents. Another promising combination, but with limiting toxicities, is a concurrent immuno- and molecular-targeted therapy. It is suspected that complimentary usage of these drugs may lead to synergism, providing robust and quick tumour responses as well as long-lasting effects. Results of currently ongoing clinical trials that investigate combination strategies in melanoma are expected to provide more mature data about the effectiveness and the safety profile of those therapies. Until more robust results of these studies occur, the best management of advanced and metastatic melanoma is immunotherapy with anti-PD1 drugs or targeted therapy with concomitant BRAF and MEK inhibitor. However, which of these two options should be used first is still under discussion.

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

    Science.gov (United States)

    Roberts, E; Norris, P

    2001-02-09

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

  18. 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

  19. Drug: D07334 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01728 ... Tricyclic antidepressant Chemical group: DG01542 ... Tricyclic antidepressant, imipramine type SLC6A4... D07334 Drug Imipraminoxide (INN) ... C19H24N2O D07334.gif ... Neuropsychiatric agent ...

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

    Science.gov (United States)

    Lövdahl, U; Riska, A; Riska, E

    1999-12-01

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

  1. Molecular and cellular mechanisms of antidepressant action.

    Science.gov (United States)

    Sharp, Trevor

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    International Nuclear Information System (INIS)

    Malatynska, E.; Knapp, R.J.; Ikeda, M.; Yamamura, H.I.

    1988-01-01

    Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated 36 Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced by them

  6. Selection and measurement of control antidepressants in clinical tests for Chinese: A systematic review.

    Science.gov (United States)

    Liu, Hao; Yang, Zhi-Min; Geng, Ying; Yang, Huan; Zhao, De-Heng; Xiao, Wei-Dong; Wang, Gao-Hua

    2017-10-01

    The study aims to help domestic application units and research institutions improve their research quality of antidepressant clinical tests by studying and analyzing the current status and problems in selecting control drugs during domestic antidepressant clinical tests and illustrating some key problems that should be noted when selecting the control drug in such researches. Considering the current domestic and overseas status of control drug selection in antidepressant clinical tests, various considerations, and misunderstandings on control drug selection in domestic antidepressant clinical tests were clarified and described, and possible factors that may influence the absolute effect of antidepressants were analyzed. Furthermore, problems that should be noted in selecting control drugs for the antidepressant clinical test, especially the placebo control, were stated. During the antidepressant clinical research, selecting placebo controls conform to moral philosophy and safety requirements. To verify the absolute effect of a test drug, a placebo control should be set or 3-arm tests should be conducted as far as possible. Possible factors that may affect the absolute effect of the test drug, including illness severity of the subject at baseline and research scale, should be given consideration. Application units and research institutions should consider the selection of subjects, control the failure rate, strengthen safety risks, and control and intensify quality control to further improve the overall quality and research level of domestic antidepressant clinical tests.

  7. Selection and measurement of control antidepressants in clinical tests for Chinese

    Science.gov (United States)

    Liu, Hao; Yang, Zhi-Min; Geng, Ying; Yang, Huan; Zhao, De-Heng; Xiao, Wei-Dong; Wang, Gao-Hua

    2017-01-01

    Abstract Objective: The study aims to help domestic application units and research institutions improve their research quality of antidepressant clinical tests by studying and analyzing the current status and problems in selecting control drugs during domestic antidepressant clinical tests and illustrating some key problems that should be noted when selecting the control drug in such researches. Methods: Considering the current domestic and overseas status of control drug selection in antidepressant clinical tests, various considerations, and misunderstandings on control drug selection in domestic antidepressant clinical tests were clarified and described, and possible factors that may influence the absolute effect of antidepressants were analyzed. Furthermore, problems that should be noted in selecting control drugs for the antidepressant clinical test, especially the placebo control, were stated. Results: During the antidepressant clinical research, selecting placebo controls conform to moral philosophy and safety requirements. To verify the absolute effect of a test drug, a placebo control should be set or 3-arm tests should be conducted as far as possible. Possible factors that may affect the absolute effect of the test drug, including illness severity of the subject at baseline and research scale, should be given consideration. Conclusions: Application units and research institutions should consider the selection of subjects, control the failure rate, strengthen safety risks, and control and intensify quality control to further improve the overall quality and research level of domestic antidepressant clinical tests. PMID:29069004

  8. [Fatal outcome after overdosage with antidepressants].

    Science.gov (United States)

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

    2014-02-10

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

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Ioannidis John PA

    2008-05-01

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

  11. Chemometrics: A new scenario in herbal drug standardization.

    Science.gov (United States)

    Bansal, Ankit; Chhabra, Vikas; Rawal, Ravindra K; Sharma, Simant

    2014-08-01

    Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA) are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency.

  12. Pediatric Tricyclic Antidepressant Poisoning: Approach and Management

    OpenAIRE

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

    2016-01-01

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

  13. Monitoring patients on chronic treatment with antidepressants between 2003 and 2011: analysis of factors associated with compliance.

    Science.gov (United States)

    Serna, M Catalina; Real, Jordi; Cruz, Inés; Galván, Leonardo; Martin, Elisabet

    2015-11-26

    Clinical practice guidelines consider the use of antidepressants as one of the standard treatments for anxiety disorders, due to the significant improvements obtained in quality of life and functional disability. In addition, in patients who have not achieved a favorable response after 3 months of psychotherapy, antidepressants are recommended as part of a combined treatment approach. This combination with psychotropic drugs and psychotherapy appears to be indicated from baseline in patients with moderate, severe or recurrent depression. In the last decade, antidepressant prescription rates in general practice have increased between 4 and 10 times. Depression presents high rates of relapse and recurrence. Treatment is often interrupted prematurely, leading to increases in both relapse rates and health care costs. Few studies have analysed the chronic use of antidepressant drugs and long-term adherence. To evaluate compliance with antidepressant treatment between 2003 and 2011 and to explore the associated factors. Retrospective cohort study of antidepressant dispensing. Health Region of Lleida between 2003 and 2011. Patients with chronic prescription of antidepressants (ATC code NO6A) during 2003 were followed up until December 2011. The sample comprised 3684 subjects. The compliance rate was calculated on the basis of the number of units withdrawn from the pharmacy and the theoretical number of units required according to the scheduled duration of treatment: compliance was defined in cases with scores greater than or equal to 80%. 12.5% of patients received chronic antidepressant treatment for at least 4 years. Mean age was 54 years, and 73.2% of patients were female. Almost a third (32.4%) presented anxiety disorders and 26.5% mood disorders. The overall compliance rate was 22% (28% in patients with depression, and 21% in patients with anxiety). According to gender, compliance rates were 21.4% for males and 22.4% for females. Compliance was more likely in

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

    Science.gov (United States)

    Muzik, Maria; Hamilton, Susan E

    2016-11-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  16. Synthesis and anti-depressant evaluation of novel pyrazolone derivatives

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Merugumolu

    2016-06-01

    Full Text Available Diazotization of substituted anilines with NaNO2 and concentrated hydrochloric acid at 0ºC gave the diazonium chlorides. Coupling of substituted aryl diazonium chlorides with ethyl acetoacetate in methanol gave ethyl-2-aryl-hydrazono-3-oxobutyrates (2a-h. Reaction of (2a-h with naphthoic carbohydrazide (3 gave the title compounds pyrazolone derivatives (4a-h. The newly synthesized compounds were screened for their in vivo anti-depressant activity by tail suspension test and forced swimming test. Some of the tested compounds 4f, 4g showed very good activity when compared to the standard drug imipramine. The newly synthesized compounds were characterized by physical parameters and the structures were elucidated by spectral data.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

    2015-10-01

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

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

    Science.gov (United States)

    Ghorpade, V.A.P.

    2005-01-01

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

  20. Systematic derivation of an Australian standard for Tall Man lettering to distinguish similar drug names.

    Science.gov (United States)

    Emmerton, Lynne; Rizk, Mariam F S; Bedford, Graham; Lalor, Daniel

    2015-02-01

    Confusion between similar drug names can cause harmful medication errors. Similar drug names can be visually differentiated using a typographical technique known as Tall Man lettering. While international conventions exist to derive Tall Man representation for drug names, there has been no national standard developed in Australia. This paper describes the derivation of a risk-based, standardized approach for use of Tall Man lettering in Australia, and known as National Tall Man Lettering. A three-stage approach was applied. An Australian list of similar drug names was systematically compiled from the literature and clinical error reports. Secondly, drug name pairs were prioritized using a risk matrix based on the likelihood of name confusion (a four-component score) vs. consensus ratings of the potential severity of the confusion by 31 expert reviewers. The mid-type Tall Man convention was then applied to derive the typography for the highest priority drug pair names. Of 250 pairs of confusable Australian drug names, comprising 341 discrete names, 35 pairs were identified by the matrix as an 'extreme' risk if confused. The mid-type Tall Man convention was successfully applied to the majority of the prioritized drugs; some adaption of the convention was required. This systematic process for identification of confusable drug names and associated risk, followed by application of a convention for Tall Man lettering, has produced a standard now endorsed for use in clinical settings in Australia. Periodic updating is recommended to accommodate new drug names and error reports. © 2014 John Wiley & Sons, Ltd.

  1. Effects of central nervous system drugs on driving: speed variability versus standard deviation of lateral position as outcome measure of the on-the-road driving test.

    Science.gov (United States)

    Verster, Joris C; Roth, Thomas

    2014-01-01

    The on-the-road driving test in normal traffic is used to examine the impact of drugs on driving performance. This paper compares the sensitivity of standard deviation of lateral position (SDLP) and SD speed in detecting driving impairment. A literature search was conducted to identify studies applying the on-the-road driving test, examining the effects of anxiolytics, antidepressants, antihistamines, and hypnotics. The proportion of comparisons (treatment versus placebo) where a significant impairment was detected with SDLP and SD speed was compared. About 40% of 53 relevant papers did not report data on SD speed and/or SDLP. After placebo administration, the correlation between SDLP and SD speed was significant but did not explain much variance (r = 0.253, p = 0.0001). A significant correlation was found between ΔSDLP and ΔSD speed (treatment-placebo), explaining 48% of variance. When using SDLP as outcome measure, 67 significant treatment-placebo comparisons were found. Only 17 (25.4%) were significant when SD speed was used as outcome measure. Alternatively, for five treatment-placebo comparisons, a significant difference was found for SD speed but not for SDLP. Standard deviation of lateral position is a more sensitive outcome measure to detect driving impairment than speed variability.

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

    Science.gov (United States)

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

    2006-11-15

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

  3. Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Helfer, Bartosz; Samara, Myrto T; Huhn, Maximilian; Klupp, Elisabeth; Leucht, Claudia; Zhu, Yikang; Engel, Rolf R; Leucht, Stefan

    2016-09-01

    The authors examined the safety and efficacy of antidepressants added to antipsychotic drugs in the treatment of schizophrenia. Multiple databases and previous publications were searched through June 2015 to identify all randomized controlled trials of any add-on antidepressants compared with placebo or no-treatment in schizophrenia. Depressive and negative symptoms (primary outcomes), overall symptoms, positive symptoms, side effects, exacerbation of psychosis, and responder rates were examined. Subgroup, meta-regression, and sensitivity analyses were performed, as well as investigations of publication bias and risk of bias. Eighty-two randomized controlled trials with a total of 3,608 participants were included. Add-on antidepressants appeared more efficacious than controls for depressive symptoms (standardized mean difference: -0.25, 95% CI=-0.38 to -0.12), negative symptoms (standardized mean difference: -0.30, 95% CI=-0.44 to -0.16), overall symptoms (standardized mean difference: -0.24, 95% CI=-0.39 to -0.09), positive symptoms (standardized mean difference: -0.17, 95% CI=-0.33 to -0.01), quality of life (standardized mean difference: -0.32, 95% CI=-0.57 to -0.06), and responder rate (risk ratio: 1.52, 95% CI=1.29 to 1.78; number-needed-to-treat-to-benefit: 5, 95% CI=4 to 7). The effects on depressive and negative symptoms appeared more pronounced when minimum thresholds of these symptoms were inclusion criteria (standardized mean difference: -0.34, 95% CI=-0.58 to -0.09 and standardized mean difference: -0.58, 95% CI=-0.94 to -0.21, respectively). There were no significant differences between antidepressants and controls in terms of exacerbation of psychosis, premature discontinuation, and the number of participants with at least one adverse event. More patients taking add-on antidepressants suffered from abdominal pain, constipation, dizziness, and dry mouth. Analysis of primary outcomes (depressive and negative symptoms) suggests small, beneficial effects

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

    Science.gov (United States)

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

    2014-02-01

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

  5. Antidepressant-Induced Female Sexual Dysfunction.

    Science.gov (United States)

    Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

    2016-09-01

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

  6. Neurogenesis and the Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

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

  7. Neurogenesis and The Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    Homer1a is upregulated by several different antidepressant measures, including non-pharmacological treatments, like sleep deprivation (SD) and electroconvulsive therapy (ECT) and antidepressant drugs, such as imipramine, fluoxetine and ketamine. Homer1a induction might thus be a crucial joint

  9. [Biomarkers for Mood Disorders and a Novel Antidepressant (R)-ketamine].

    Science.gov (United States)

    Hashimoto, Kenji

    2017-10-01

    Depression is often misdiagnosed as major depressive disorder in patients with bipolar disorder. Therapeutic drugs for these two disorders are quite different, but the anesthetic ketamine shows fast-acting antidepressant effects in treatment-resistant patients with these disorders. Here, we discuss biomarkers for both disorders, recent findings regarding ketamine, and predictable biomarkers for ketamine's antidepressant actions.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. [Depressive symptoms during anorexia nervosa: State of the art and consequences for an appropriate use of antidepressants].

    Science.gov (United States)

    Leblé, N; Radon, L; Rabot, M; Godart, N

    2017-02-01

    -line treatment, after appropriate refeeding, and in case of an authentic depressive disorder. Those data appear to be in contradiction with the frequent use of those drugs in clinical practice. Nevertheless, clinical trials assessing antidepressant treatment in AN suffer from methodological weakness concerning the size of the sample, the choice of the population or the evaluation criterion. This lack of proof must raise our vigilance concerning antidepressant medication in AN but should not categorically prevent the clinician from using it when necessary. We do believe that there are some indications for prescribing antidepressant in patients with AN. The clinical challenge lies in the differentiation of the depressive symptoms that are transitory and likely to improve without medication from those that signal the presence of an MDD. Three criterion could be indicative of MDD: familial history of mood disorder, as it is a major risk factor for MDD among relatives; the chronology of appearance of both disorders, when MDD pre-exists AN; a few specific symptoms cannot be attributed to undernourishment or reactive depressive signs, such as morning insomnia, daily variation of depressive symptoms, suicidal attempts or ideation and guilt ideation. Thus, in integrating the data from the literature review, we propose a pragmatic therapeutic strategy for the use of an antidepressant in AN during adolescence that lies in 3 main categories for depressive manifestations in AN: therapeutic emergencies: when an obvious and severe MDD is comorbid to AN, immediate antidepressant would be required; isolated and non-specific depressive sign: no medication would be relevant as they are supposed to improve with refeeding and psychotherapeutic support; intermediary patterns which is probably the most frequent situation. In the last case, it would be relevant to abstain from prescribing medication in first line, but an antidepressant medication should be quickly considered in the presence of one (or

  12. Antidepressant-like effects of methanolic extract of Bacopa monniera in mice.

    Science.gov (United States)

    Mannan, Abdul; Abir, Ariful Basher; Rahman, Rashidur

    2015-09-25

    Bacopa monniera has been used as a cure for various ailments that include anxiety, epileptic disorders, dementia, blood purifier, cough and rheumatism, and some important local uses of the plant are in dermatitis, anemia, diabetes, promote fertility and prevent miscarriage for many years in Bangladesh. According to this background, the aim of the study was to evaluate the antidepressant-like effect of the methanolic extract of B. monniera (MEBM) in different behavioral models such as forced swimming test (FST), measurement of locomotor activity test (MLAT) and tail suspension test (TST) on mice after two weeks treatment. Mice were divided into five groups (n = 5/group): control group (deionized water), standard group where Imipramine hydrochloride (30 mg/kg) was used as standard drug and three test groups where three doses of the methanolic extract of B. monniera (MEBM) (50, 100, and 200 mg/kg) was used for two weeks treatment. All the drug and test samples were administered via gavage through oral route. To assess the antidepressant-like effect of MEBM forced swimming test (FST), tail suspension test (TST) and measurement of locomotor activity test (MLAT) have been done in mice. The results showed that a strong and dose-dependent antidepressant effects in different mice models. The main findings of the MEBM significantly reduced the duration of immobility times in the forced swimming test (p < 0.001). Likewise, the extract significantly decreased the immobility time in the tail suspension test (p < 0.001). Moreover, we employed an additional measurement of locomotor activity test to check the motor stimulating activity of the MEBM. The extract also significantly increased the locomotion, rearing and defecation effects in comparison to the control group (p < 0.001). The present results clearly demonstrate that the methanolic extract of B. monniera possesses antidepressant-like activity in the animal behavioral models. The current study warrants

  13. Use of antidepressants and risk of epithelial ovarian cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  14. Antidepressants and advertising: psychopharmaceuticals in crisis.

    Science.gov (United States)

    Greenslit, Nathan P; Kaptchuk, Ted J

    2012-03-01

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

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Ingeborg Hartz

    2011-12-01

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

  17. Antidepressants for cocaine dependence and problematic cocaine use.

    Science.gov (United States)

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

    2011-12-07

    statistically significant differences in favour of antidepressants.Antidepressants versus other drugs: Comparing antidepressants with dopamine agonists or with anticonvulsants, no evidence of differences was shown on dropouts and on other outcomes (abstinence from cocaine use, adverse events). At the current stage of evidence data do not support the efficacy of antidepressants in the treatment of cocaine abuse/dependence. Partially positive results obtained on secondary outcome measures, such as depression severity, do not seem to be associated with an effect on direct indicators of cocaine abuse/dependence. Antidepressants cannot be considered a mainstay of treatment for unselected cocaine abusers/dependents.

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

    Directory of Open Access Journals (Sweden)

    Mariam B. Camacho

    2017-12-01

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

  19. Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants.

    Science.gov (United States)

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

    2014-11-01

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

  20. Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

    Directory of Open Access Journals (Sweden)

    Jona Kräenbring

    Full Text Available The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001. Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001 and highest in the category "indication" (91.3% ± 2.0% when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

  1. Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology

    Science.gov (United States)

    Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

    2014-01-01

    The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7%±0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8±1.5% (ptextbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6±1.6 references and 262.8±37.4 edits performed by 142.7±17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education. PMID:25250889

  2. Detection of systemic hypersensitivity to drugs using standard guinea pig assays.

    Science.gov (United States)

    Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L

    2003-12-01

    The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

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

    African Journals Online (AJOL)

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

  4. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  5. Assessment of Sexual Dysfunction Symptoms in Female Drug Users: Standardized vs. Unstandardized Methods.

    Science.gov (United States)

    Diehl, Alessandra; Rassool, G Hussein; dos Santos, Manoel Antônio; Pillon, Sandra Cristina; Laranjeira, Ronaldo

    2016-01-01

    The aim of this study is to evaluate whether there is a difference in the identified prevalence between the assessment of symptoms of sexual dysfunction in female drug users using a standardized scale and by means of a nonstandardized set of questions about sexual dysfunctions. A cross-sectional study was conducted with two groups of substance-dependent women using the Drug Abuse Screening Test, the Short Alcohol Dependence Data questionnaire, the Fagerström Test for Nicotine Dependence for the evaluation of the severity of dependence, and the Arizona Sexual Experience Scale. In both groups, the severity of dependence and the prevalence of symptoms of sexual dysfunctions in women were similar. The use of standardized and nonstandardized instruments to assess sexual dysfunction symptoms is an essential resource for the provision of good-quality care to this clientele.

  6. Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

    Science.gov (United States)

    Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

    2017-06-23

    The equilibrium dissociation constant (K D ) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the K D value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative K D values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The K D values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the K D values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

    Science.gov (United States)

    Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

    2017-05-01

    To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

  8. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (French Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  9. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (Spanish Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  10. Interaction of antidepressants with the serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Sørensen, Lena; Andersen, Jacob; Thomsen, Mette

    2012-01-01

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

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

    Science.gov (United States)

    Wilson, Sue; Argyropoulos, Spilios

    2005-01-01

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

  12. 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 ...

  13. Polypyrrole/magnetic nanoparticles composite as an efficient sorbent for dispersive micro-solid-phase extraction of antidepressant drugs from biological fluids.

    Science.gov (United States)

    Asgharinezhad, Ali Akbar; Karami, Sara; Ebrahimzadeh, Homeira; Shekari, Nafiseh; Jalilian, Niloofar

    2015-10-15

    In this study, polypyrrole/magnetic nanoparticles composites in the presence of two different dopants were synthesized with the aid of chemical oxidative polymerization process for dispersive-μ-solid phase extraction (D-μ-SPE). The synthesized magnetic sorbents were characterized by various techniques. The results exhibited that the nanocomposite modified by polypyrrole with sodium perchlorate as a dopant demonstrated higher extraction efficiency for citalopram (CIT) and sertraline (STR) as the model compounds. This nanosorbent in combination with high performance liquid chromatography-UV detection was applied for extraction, preconcentration and determination of CIT and STR in urine and plasma samples. The effect of various parameters on the extraction efficiency including: sample pH, amount of sorbent, sorption time, eluent and its volume, salt content, and elution time were investigated and optimized. The opted conditions were: sample pH, 9.0; sorbent dosage, 10mg; sorption time, 7 min; elution solvent and its volume, 0.06 mol L(-1) HCl in methanol, 120 μL; elution time, 2 min and without addition of salt to the sample. The calibration curves were linear in the concentration range of 1-800 μg L(-1). The limits of detection (LODs) were obtained in the range of 0.2-1.0 μg L(-1) for CIT and 0.3-0.7 μg L(-1) for STR, respectively. The percent of extraction recoveries and relative standard deviations (n=5) were in the range of 93.4-99, 4.8-8.4 for CIT and 94-98.4, 4.3-9.2 for STR, respectively. Finally, the applicability of the method was successfully confirmed by the extraction and determination of CIT and STR in human urine and plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Determination of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, desipramine, clomipramine and desmethylclomipramine in dried blood spots using LC-MS/MS

    NARCIS (Netherlands)

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

    2013-01-01

    Background: Therapeutic Drug Monitoring (TDM) of Tricyclic Antidepressants (TADs) is considered useful in patients with major depressive disorders, since these drugs display large individual differences in clearance and therapeutic windows of these drugs are relatively small. We developed an assay

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

    Science.gov (United States)

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

    2008-04-01

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

  16. Increased risk of antidepressant use in childhood cancer survivors

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT₁A and 5-HT₇ Antagonists in Animal Models.

    Directory of Open Access Journals (Sweden)

    Karolina Pytka

    Full Text Available The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxyethoxy]ethyl}-4-(2-methoxyphenylpiperazynine hydrochloride (HBK-14 and 2-[2-(2-chloro-6-methylphenoxyethoxy]ethyl-4-(2- methoxyphenylpiperazynine dihydrochloride (HBK-15 in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT2, adrenergic α1, and dopaminergic D2 receptors as well as being full 5-HT1A and 5-HT7 receptor antagonists. We also present their potent antidepressant-like activity (HBK-14-FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg and (HBK-15-FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg. We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT1A receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds.

  18. Body weight as a predictor of antidepressant efficacy in the GENDEP project

    DEFF Research Database (Denmark)

    Uher, Rudolf; Mors, Ole; Hauser, Joanna

    2009-01-01

    Background: Being overweight or obese may be associated with poor response to antidepressants. The present report explores the moderation of antidepressant response by body weight to establish the specificity to antidepressant mode of action, type of depressive symptoms and gender. Methods: Height....... The relationship between body weight and change in neurovegetative symptoms was moderated by gender with obese men responding less to nortriptyline and obese women having poorer response to both antidepressants. Limitations: As no placebo arm was included, the specificity of findings to antidepressants is relative...... and weight were measured in 797 men and women with major depression treated with escitalopram or nortriptyline for twelve weeks as part of the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Body mass index (BMI) and obesity (BMI > 30) were tested as predictors of change in depressive...

  19. Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian

    2017-01-01

    to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population...... between 1995 and 2010 in the Danish Prescription Register and compared the prevalence and incidence of use of antidepressants, sedatives and antipsychotics. The prevalence of antidepressant use by women was lower in 1998 but no different from that in controls in 2003 and 2008; the prevalence...... of antidepressant use by men was higher in both 1998 and 2008 than in the Danish population. The incidence of antidepressant use was lower for female members in 1996–2000, but no difference was observed in the other periods. The prevalence and incidence of use of sedatives and antipsychotics did not consistently...

  20. A review on the status of quality control and standardization of herbal drugs in India

    Directory of Open Access Journals (Sweden)

    Anju Dhiman

    2016-01-01

    Full Text Available Background: Most of the herbal medicines in the world originate from the developing countries. There are ample opportunities for these countries to expand their global export. The world market for botanical medicines including drug products and raw materials has been estimated to have an annual growth rate between 5% and 15%. Total global botanical drug market is estimated at US$62 billion and is expected to grow to the tune of US$5 trillion by the year 2050. In the USA alone, the usage of botanicals has been increased by 380% between the years 1990 and 1997. Materials and Methods: Ayurveda, the Indian system of medicine, is one of the ancient, yet living traditions that face a typical Western bias. Widespread and growing use of botanicals has created public health challenges globally in terms of quality, safety, and efficacy. Results and Discussion: The development of parameters for standardization and quality control of botanicals is a challenging task. Various regulatory authorities, research organizations, and botanical drug manufacturers have contributed in developing guiding principles and addressing issues related to the quality, safety, and efficacy. Conclusions: The present review describes the regulatory aspects of herbal drugs in India and various other countries.

  1. Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice

    DEFF Research Database (Denmark)

    Rosenberg, Jacob

    2016-01-01

    researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict......Zeng et al.'s Ethics Review highlights some of the challenges associated with clinical research in China. They found that only a minority of published clinical trials of anti-dementia drugs reported that they fulfilled the basic ethical principles as outlined in the Declaration of Helsinki....... With recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical...

  2. Antidepressant, anxiolytic and anti-nociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch leaves in mice model

    Directory of Open Access Journals (Sweden)

    Mohammad Shah Hafez Kabir

    2015-11-01

    Full Text Available Objective: To estimate the antidepressant, anxiolytic and antinociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch (S. colocasiifolia leaves. Methods: Swiss albino mice treated with 1% Tween solution, standard drugs and ethanol extract of S. colocasiifolia, respectively, were subjected to the neurological and antinociceptive investigations. The tail suspension test and forced swimming test were used for testing antidepressant activity, where the parameter is the measurement of immobility time. Anxiolytic activity was evaluated by hole board model. Anti-nociceptive potential of the extract was also screened for centrally acting analgesic activity by using formalin induced licking response model and acetic acid induced writhing test was used for testing peripheral analgesic action. Results: Ethanol extract of S. colocasiifolia significantly decreased the period of immobility in both tested models (tail suspension and forced swimming models of antidepressant activity. In the hole board model, there was a dose dependant (at 100 and 200 mg/kg and a significant increase in the number of head dipping by comparing with control (1% Tween solution (P < 0.05 and P < 0.001. In formalin induced licking model, a significant inhibition of pain compared to standard diclofenac sodium was observed (P < 0.05 and P < 0.001. In acetic acid induced test, there was a significant reduction of writhing response and pain in mice treated with leaves extract of S. colocasiifolia at 200 mg/kg body weight (P < 0.05 and P < 0.001. Conclusions: The results proofed the prospective antidepressant, anxiolytic and antinociceptive activities of ethanol extract of S. colocasiifolia leaves.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2007-01-01

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

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

    Science.gov (United States)

    Howland, Robert H

    2007-07-01

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

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

    Science.gov (United States)

    Bérard, Anick; Ramos, Elodie

    2007-11-01

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

  7. Food and drug administration. Radiation protection standards and recommendations for electronic products: the development process

    International Nuclear Information System (INIS)

    Little, M.S.

    1980-01-01

    The Food and Drug Administration is responsible for maintaining a national program to protect the public health from unnecessary and harmful radiation emitted by radiation products. This program involves the promulgation and implementation of mandatory and voluntary standards to promote safe and effective design and use of such products. This paper describes the process by which electronic product radiation safety standards and recommendations are developed. To assist the agency in the development effort and to achieve a sound technological and scientific basis and risk/benefit assessment, it is important that knowledgeable professionals, industrial representatives, and consumers participate in that process. This paper is designed to provide useful information to aid anyone wishing to participate more effectively. (author)

  8. Antidepressant efficacy and side-effect burden: a quick guide for clinicians

    Directory of Open Access Journals (Sweden)

    Daniel Santarsieri

    2015-10-01

    Full Text Available Prescribing of antidepressant treatment (ADT for major depressive disorder (MDD has increased in quantity and popularity over the last two decades. This is likely due to the approval of safer medications, better education of clinicians and their patients, direct-to-consumer marketing practices, and less stigma associated with those taking ADT. This trend has also been met with some controversy, however, as the ongoing safety and effectiveness of these treatments have at times been called into question. This paper discusses the differing levels of evidence that support the use of ADT based on (A Food and Drug Administration approvals, (B data from randomized controlled trials or meta-analyses and, where these are not available, the authors discuss and apply, (C theoretical pharmacodynamic principles to justify antidepressant choice in the treatment of MDD patients. The final section discusses standard psychopharmacology guideline approaches to better alert the reader as to which practices are commonplace compared with those which are more outside of the standard of care.

  9. Antidepressant efficacy and side-effect burden: a quick guide for clinicians.

    Science.gov (United States)

    Santarsieri, Daniel; Schwartz, Thomas L

    2015-01-01

    Prescribing of antidepressant treatment (ADT) for major depressive disorder (MDD) has increased in quantity and popularity over the last two decades. This is likely due to the approval of safer medications, better education of clinicians and their patients, direct-to-consumer marketing practices, and less stigma associated with those taking ADT. This trend has also been met with some controversy, however, as the ongoing safety and effectiveness of these treatments have at times been called into question. This paper discusses the differing levels of evidence that support the use of ADT based on (A) Food and Drug Administration approvals, (B) data from randomized controlled trials or meta-analyses and, where these are not available, the authors discuss and apply, (C) theoretical pharmacodynamic principles to justify antidepressant choice in the treatment of MDD patients. The final section discusses standard psychopharmacology guideline approaches to better alert the reader as to which practices are commonplace compared with those which are more outside of the standard of care.

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

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  11. Antidepressants versus placebo for panic disorder in adults.

    Science.gov (United States)

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

    2018-04-05

    ) allocating adults with panic disorder to antidepressants or placebo. Two review authors independently checked eligibility and extracted data using a standard form. We entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details and settings. Primary outcomes included failure to respond, measured by a range of response scales, and treatment acceptability, measured by total number of dropouts for any reason. Secondary outcomes included failure to remit, panic symptom scales, frequency of panic attacks, agoraphobia, general anxiety, depression, social functioning, quality of life and patient satisfaction, measured by various scales as defined in individual studies. We used GRADE to assess the quality of the evidence for each outcome MAIN RESULTS: Forty-one unique RCTs including 9377 participants overall, of whom we included 8252 in the 49 placebo-controlled arms of interest (antidepressant as monotherapy and placebo alone) in this review. The majority of studies were of moderate to low quality due to inconsistency, imprecision and unclear risk of selection and performance bias.We found low-quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants = 6500; studies = 30). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means seven people would need to be treated with antidepressants in order for one to benefit. We observed the same finding when classes of antidepressants were compared with placebo.Moderate-quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause (RR 0.88, 95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of

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

    Science.gov (United States)

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

    2013-05-01

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

  13. 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

  14. Integrity, standards, and QC-related issues with big data in pre-clinical drug discovery.

    Science.gov (United States)

    Brothers, John F; Ung, Matthew; Escalante-Chong, Renan; Ross, Jermaine; Zhang, Jenny; Cha, Yoonjeong; Lysaght, Andrew; Funt, Jason; Kusko, Rebecca

    2018-03-15

    The tremendous expansion of data analytics and public and private big datasets presents an important opportunity for pre-clinical drug discovery and development. In the field of life sciences, the growth of genetic, genomic, transcriptomic and proteomic data is partly driven by a rapid decline in experimental costs as biotechnology improves throughput, scalability, and speed. Yet far too many researchers tend to underestimate the challenges and consequences involving data integrity and quality standards. Given the effect of data integrity on scientific interpretation, these issues have significant implications during preclinical drug development. We describe standardized approaches for maximizing the utility of publicly available or privately generated biological data and address some of the common pitfalls. We also discuss the increasing interest to integrate and interpret cross-platform data. Principles outlined here should serve as a useful broad guide for existing analytical practices and pipelines and as a tool for developing additional insights into therapeutics using big data. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    Science.gov (United States)

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

    DEFF Research Database (Denmark)

    Galling, B; Vernon, J A; Pagsberg, A K

    2018-01-01

    OBJECTIVE: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. METHODS: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing...... adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval.......77, -0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04-2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation...

  17. Migraine Medications and Antidepressants: A Risky Mix?

    Science.gov (United States)

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

  18. The role of mTOR in depression and antidepressant responses.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Neotti, Morgana V; Quevedo, João

    2014-04-17

    The aim of this study was to characterize the mTOR signaling cascade in depression and the actions that antidepressant drugs have on this pathway. Herein, a literature review was performed by verification and comparison of textbooks and journal articles that describe the characterization of the mTOR signaling cascade and its relationship to depression and antidepressant drugs, especially ketamine. Postmortem studies have shown robust deficits in the mammalian target of rapamycin (mTOR) signaling in the prefrontal cortex of subjects diagnosed with major depressive disorder. However, besides the mTOR signaling pathway having an antidepressant response to various drugs, this seems to be more associated with antidepressant N-methyl-d-aspartate (NMDA) receptor antagonists, such as ketamine. The characterization of the mTOR signaling pathway in depression and its action in response to antidepressants show great potential for the identification of new therapeutic targets for the development of antidepressant drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. 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...

  20. Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: A case report

    Directory of Open Access Journals (Sweden)

    Hassan Amiri

    2016-12-01

    Full Text Available Poisoning with tricyclic antidepressants is an important cause of drug-related self-poisoning in the developed world and a very common cause of poisoning and mortality in developing countries. Electrocardiographic manifestations of most tricyclic antidepressant-poisoned patients resolve by the administration of 1–2 mEq/kg of sodium bicarbonate. Some rare cases have been reported who have been resistant to the long-term or high doses of bicarbonate administration. We present a case of acute tricyclic antidepressant toxicity referring with status epilepticus, hypotension, and refractory QRS complex widening that resolved after the intravenous administration of 2650 mEq sodium bicarbonate.

  1. 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.

  2. 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

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

    DEFF Research Database (Denmark)

    Liebenberg, Nico

    2010-01-01

    therapy of depression. A recent study from our laboratory reported an antidepressant-like response in the rat forced swim test (FST) following chronic (11 day) co-administration of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the muscarinic acetylcholine (mACh) receptor antagonist atropine...... in Sprague Dawley rats. In the current study we explored the antidepressant-like properties of PDE5 inhibitors in Flinders Sensitive Line (FSL) rats, a genetic animal model of depression, and investigated the mechanism(s) that may be involved in the antidepressant-like activity of these drugs. We also......Major depression is one of the most debilitating diseases of our time, while current antidepressant treatments remain deficient in several ways. The nitric oxide (NO) / cyclic guanosine monophosphate (cGMP) / cGMP-dependent protein kinase (PK-G) pathway shows promise as a novel target for the drug...

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

    OpenAIRE

    Sharma, Verinder; Sommerdyk, Christina

    2013-01-01

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

  5. Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

    Science.gov (United States)

    Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

    2014-01-01

    The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

  6. Standards of the Network of Colleges and Universities Committed to the Elimination of Drug and Alcohol Abuse.

    Science.gov (United States)

    Office of Educational Research and Improvement (ED), Washington, DC.

    The background, goals and standards of the Network of Colleges and Universities Committed to the Elimination of Drug and Alcohol Abuse are described. The network was formed in 1987 at the instigation of the Office of Educational Research and Improvement, U.S. Department of Education. A planning group met to establish the standards for…

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2008-12-01

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

  9. Antidepressants and the risk of hyponatremia

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2000-11-01

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

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

    OpenAIRE

    Danilevičiūtė, Vita; Sveikata, Audrius

    2002-01-01

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

  12. Antidepressant-Like Activity of Ethanol Extract of Ganoderma lucidum (Reishi in Mice

    Directory of Open Access Journals (Sweden)

    Aslam Muhammad

    2017-05-01

    Full Text Available Ganoderma lucidum, known as “Lingzhi” in China, is one among greatly regarded fungi around the world. In old Chinese encyclopedias of medical “Shen Nong’s Ben Cao Jing” and “Ben Cao Gang Mu”, it is rated as extraordinarily precious fungus. In this study, antidepressant activity of ethanol extract of Ganoderma lucidum has been assessed. The extract was given orally by gavage at the dose of 20 mg/kg, 75 mg/kg, and 130 mg/kg body weight. Fluoxetine (20 mg/kg p.o. was used as the standard drug. The results of our study show that Ganoderma lucidum significantly decreased immobility time in forced swim test and tail suspension test. Open field test was used to assess locomotor activity of the mice to exclude the false positive results. In open field test, Ganoderma lucidum didn’t affect the total movement and ambulatory movement at the same doses that significantly reduced immobility time in the forced swim test and tail suspension test. Thus, it is concluded that ethanol extract of Ganoderma lucidum has antidepressant activity in mice.

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

    Science.gov (United States)

    Irarrázaval O, María Elisa; Gaete G, Leonardo

    2016-10-01

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

  14. Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

    Directory of Open Access Journals (Sweden)

    Shin Minkyu

    2010-11-01

    Full Text Available Abstract Background The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. Results We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine. a selective serotonin reuptake inhibitor (fluoxetine, a monoamine oxidase inhibitor (phenelzine and psychoactive herbal extracts of Nelumbinis Semen (NS. To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced. Conclusions These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

  15. Interactions between antidepressants and antihypertensive and glucose lowering drugs among patients in the HIPERDIA Program, Coronel Fabriciano, Minas Gerais State, Brazil Interações entre antidepressivos e medicamentos e anti-hipertensivos e hipo-glicemiantes em pacientes do Programa HIPERDIA em Coronel Fabriciano, Minas Gerais, Brasil

    Directory of Open Access Journals (Sweden)

    Paula Vieira Coelho

    2009-10-01

    Full Text Available The aims of this study were to investigate the prevalence and to describe the most frequent potential interactions between antidepressants and antihypertensive and glucose lowering drugs in the HIPERDIA Program at two primary care units in Coronel Fabriciano, Minas Gerais State, Brazil. Data were collected through the patient registry in the HIPERDIA Program and the local psychoactive drug dispensing system. Interactions were classified as due to pharmacokinetic and/or pharmacodynamic mechanisms. Prevalence of antidepressant use in the HIPERDIA Program was 4.37% (29 of patient 663 records. Of the HIPERDIA patients in treatment with antidepressants, 19 were exposed to 47 interactions, 23.4% of which involving pharmacokinetic, 61.7% pharmacodynamic synergy, and 15.9% simultaneous pharmacokinetic and pharmacodynamic mechanisms. Complications can arise from drug-drug interactions, a situation that can escape the attention of prescribing health professionals.O objetivo do estudo foi investigar a prevalência e descrever as possíveis interações de medicamentos mais freqüentes entre antidepressivos e anti-hipertensivos/hipoglicemiantes do programa HIPERDIA de duas unidades básicas de saúde do Município de Coronel Fabriciano, Minas Gerais, Brasil. A coleta de dados foi realizada mediante consulta ao caderno de cadastro dos pacientes usuários do programa de HIPERDIA e pela consulta ao sistema de dispensação de psicotrópicos do município. As interações foram classificadas segundo o mecanismo farmacocinético e farmacodinâmico. A prevalência do uso de antidepressivos em pacientes do HIPERDIA foi de 4,37% (29 de 663 cadastros analisados. Dos pacientes do HIPERDIA em tratamento com antidepressivos, 19 estão expostos a 47 interações, 23,4% delas ocorrem por mecanismos farmacocinéticos, 61,7% por mecanismos farmacodinâmicos de sinergismo e 15,9% interagem das duas formas simultaneamente. Complicações podem ser provocadas por intera

  16. Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial.

    NARCIS (Netherlands)

    Kerkhoven, L.A.S. van; Laheij, R.J.F.; Aparicio, N.; Boer, W.A. de; Hazel, S. van den; Tan, A.; Witteman, B.J.M.; Jansen, J.B.M.J.

    2008-01-01

    BACKGROUND & AIMS: Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects. Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel

  17. Combined treatment with atypical antipsychotics and antidepressants in treatment-resistant depression: preclinical and clinical efficacy.

    Science.gov (United States)

    Rogóż, Zofia

    2013-01-01

    Several clinical reports have documented a beneficial effect of adding atypical antipsychotic drugs to ongoing treatments with antidepressants, particularly selective serotonin reuptake inhibitors, in ameliorating drug-resistant depression. The aim of this paper was to summarize some preclinical evidence describing the mechanism responsible for the therapeutic action of combined treatment with antidepressants and atypical antipsychotics and also some clinical data supporting the efficacy and safety of the augmentation strategy for improving antidepressant-resistant depression using atypical antipsychotics. This analysis is based on five microdialysis studies and nine behavioral studies assessing the impact of combined atypical antipsychotic and antidepressant treatments on extracellular levels of dopamine, serotonin and noradrenaline in the prefrontal cortex of freely moving rats and on antidepressant-induced effects, respectively. In addition, clinical data demonstrating the efficacy and safety of augmentation strategies for treatment-resistant depression using atypical antipsychotics were included. Combined treatment of rats with all studied atypical antipsychotics (olanzapine, risperidone, clozapine and quetiapine) and antidepressants (citalopram, fluoxetine and fluvoxamine) increased the extracellular level of dopamine in the prefrontal cortex compared to a respective drug given alone; in addition, a combination of olanzapine or quetiapine plus fluoxetine or fluvoxamine increased the levels of dopamine and noradrenaline. Moreover, atypical antipsychotics administered in a low dose enhanced the antidepressant-like activity of antidepressants, with (among other mechanisms) the serotonin 5-HT1A, 5-HT2A and adrenergic α2 receptors likely playing an important role in their action. The results support the conclusion that atypical antipsychotics may be effective as adjunctive therapy in treatment-resistant depression; however, their adverse effect profile may be

  18. Synergistic interaction between diene valepotriates from Valeriana glechomifolia Meyer (Valerianaceae) and classical antidepressants: an isobolographic analysis.

    Science.gov (United States)

    Müller, Liz G; Stolz, Eveline D; Betti, Andresa H; Herzfeldt, Vivian; Rates, Stela M K

    2015-07-01

    Combinations of different classes of antidepressants (including herbal adjuvants) have been used as an alternative means of achieving better results in the treatment of depressed patients. However, studies characterizing the interactions between herbal adjuvants and antidepressants are lacking. This study is the first to investigate the interaction between diene valepotriates (VAL) from Valeriana glechomifolia, a species with antidepressant-like effects, and imipramine (IMI), desipramine (DESI) and bupropion (BUP). The interactions were assessed via isobolographic analyses, which represent a tool for evaluating interactions between drugs. The interaction between VAL and each antidepressant was evaluated in mice given concurrent oral administration of each drug with fixed ED50 ratios and subjected to a forced swimming test (FST). Spontaneous locomotion was measured in the open field test. The drug combinations produced a dose-dependent anti-immobility effect in the FST without altering mouse locomotor activity. Isobolographic analysis revealed that VAL resulted in synergistic interactions in combination with each of the antidepressants tested. The synergistic interactions between VAL and IMI, DESI and BUP highlight the potential for VAL to serve as adjuvants to antidepressant drugs and suggest that VAL does not directly target the same sites on neuronal transporters as the antidepressants. © 2015 Royal Pharmaceutical Society.

  19. The use of antidepressants in the treatment of chronic pain. A review of the current evidence.

    Science.gov (United States)

    Magni, G

    1991-11-01

    In the last 30 years antidepressant drugs have been used increasingly in the treatment of patients with chronic pain. This article reviews the results of some 40 placebo-controlled studies. It is difficult to make comparisons between the various studies because they often differ in terms of pain conditions, patient selection, antidepressant drug used, dosages, trial design, etc. However, in spite of this heterogeneity and other methodological problems it is clear that a wide range of pain conditions are responsive to antidepressant drug treatment, in particular: headache, migraine, facial pain, neurogenic pain, fibrositis, and probably arthritis and rheumatoid arthritis. More data need to be gathered in cancer pain, and in other conditions such as low back pain for which no, or very limited, effect has been shown. The beneficial effects of antidepressant drugs is in most cases of a mild to moderate degree, some time lag is necessary before it is completely manifest, and it tends to persist over time if drug treatment is continued in the long term. Strong evidence of efficacy is not evident for all the antidepressants, and there are probably significant differences in this respect between various drugs. The effect of a drug on pain does not seem necessarily to be related to its effect on mood. Further studies are needed to clarify this topic, and it will be necessary to examine specific pain conditions, compare different antidepressants, with reference to each other and to placebo, further investigate the role of drug plasma concentrations and control for the presence of concomitant psychiatric disturbances and for organic lesions responsible for the pain symptomatology.

  20. Factors associated with switching and combination use of antidepressants in young Swedish adults

    Science.gov (United States)

    Andersson Sundell, K; Petzold, M G; Wallerstedt, S M

    2013-01-01

    Aims Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20–34 years. Methods Individuals, aged 20–34 years, who purchased an antidepressant in January–June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. Results A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93–2.57), and lower in individuals with high education: 0.64 (0.54–0.75), and shorter length of follow-up: 0.73 (0.62–0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05–2.49), and lower among individuals with short university education: 0.58 (0.43–0.78), those starting on mirtazapine: 0.78 (0.62–0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63–0.88). Conclusions One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase

  1. Factors associated with switching and combination use of antidepressants in young Swedish adults.

    Science.gov (United States)

    Andersson Sundell, K; Petzold, M G; Wallerstedt, S M

    2013-12-01

    Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20-34 years. Individuals, aged 20-34 years, who purchased an antidepressant in January-June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93-2.57), and lower in individuals with high education: 0.64 (0.54-0.75), and shorter length of follow-up: 0.73 (0.62-0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05-2.49), and lower among individuals with short university education: 0.58 (0.43-0.78), those starting on mirtazapine: 0.78 (0.62-0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63-0.88). One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase patterns were associated with socioeconomic

  2. 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.

  3. Use of antipsychotic and antidepressant within the Psychiatric Disease Centre, Regional Health Service of Ferrara.

    Science.gov (United States)

    Bianchi, Stefano; Bianchini, Erica; Scanavacca, Paola

    2011-12-20

    tended to reduce the doses of their drugs. This study highlights the tendency to follow combination therapies, prescribing SGAs together with anticholinergics in order to minimize extrapyramidal side effects or by combining two antidepressants. The study showed low adherence for both pharmaceutical therapies, which is typical in the setting of the analyzed diseases.

  4. Safety limits of antidepressant use plus combinations: focus on cardiovascular function.

    Science.gov (United States)

    Stella, Florindo; Loureiro, Julia C; Pais, Marcos V; Canineu, Paulo R; Florenza, Orestes V

    2017-12-27

    Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Antidepressants and the risk of hyponatremia: a class-by-class review of literature.

    Science.gov (United States)

    De Picker, Livia; Van Den Eede, Filip; Dumont, Glenn; Moorkens, Greta; Sabbe, Bernard G C

    2014-01-01

    Antidepressant-induced hyponatremia can cause significant morbidity and mortality. It is mostly associated with the use of selective serotonin reuptake inhibitors (SSRIs), but its frequency and class specificity are uncertain. To determine the relationship between hyponatremia and antidepressants and to define the incidence and odds ratios for antidepressant classes. A review of the literature prior to March 2013 was performed using Web of Science and PubMed by employing combinations of search strings "antidepressants" and antidepressant class and generic drug names with "hyponatr(a)emia," "SIADH," or "inappropriate ADH." Overall, 21 effect studies and more than 100 case reports were considered, most concerning SSRIs. Because of variations in study designs, populations, and cutoff values, incidence rates diverged between 0.06% and 40% for SSRIs and 0.08% and 70% for venlafaxine. Although based on less solid evidence, incidence figures for mirtazapine and tricyclic antidepressants were lower. Regarding classes, odds ratios for SSRIs (1.5-21.6) were consistently higher than for tricyclic antidepressants (TCAs) (1.1-4.9). The risks associated with monoamine oxidase inhibitors, reboxetine, and bupropion could not be established owing to insufficient information. Patient risk factors included older age (odds ratios = 6.3) and concomitant use of (thiazide) diuretics (odds ratios = 11.2-13.5). Hyponatremia is a potentially dangerous side effect of antidepressants and is not exclusive to SSRIs. Current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine, especially when combined with patient risk factors, warranting clinicians to be aware of this complication. The risks associated with mirtazapine are moderate, supporting this antidepressant as an alternative treatment for patients with (an increased risk of) hyponatremia. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. Prevalence of antidepressant prescription or use in patients with acute coronary syndrome: a systematic review.

    Directory of Open Access Journals (Sweden)

    Matthew J Czarny

    Full Text Available Depression is common among acute coronary syndrome (ACS patients and is associated with poor prognosis. Cardiac side effects of older antidepressants were well-known, but newer antidepressants are generally thought of as safe to use in patients with heart disease. The objective was to assess rates of antidepressant use or prescription to patients within a year of an ACS.PubMed, PsycINFO, and CINAHL databases searched through May 29, 2009; manual searching of 33 journals from May 2009 to September 2010. Articles in any language were included if they reported point or period prevalence of antidepressant use or prescription in the 12 months prior or subsequent to an ACS for ≥100 patients. Two investigators independently selected studies for inclusion/exclusion and extracted methodological characteristics and outcomes from included studies (study setting, inclusion/exclusion criteria, sample size, prevalence of antidepressant prescription/use, method of assessing antidepressant prescription/use, time period of assessment.A total of 24 articles were included. The majority were from North America and Europe, and most utilized chart review or self-report to assess antidepressant use or prescription. Although there was substantial heterogeneity in results, overall, rates of antidepressant use or prescription increased from less than 5% prior to 1995 to 10-15% after 2000. In general, studies from North America reported substantially higher rates than studies from Europe, approximately 5% higher among studies that used chart or self-report data.Antidepressant use or prescription has increased considerably, and by 2005 approximately 10% to 15% of ACS patients were prescribed or using one of these drugs.

  8. Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

    Directory of Open Access Journals (Sweden)

    Stimson Gerry V

    2006-03-01

    Full Text Available Abstract Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs. Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups

  9. Adherence to antidepressant medications: a randomized controlled trial of medication reminding in college students.

    Science.gov (United States)

    Hammonds, Tracy; Rickert, Krista; Goldstein, Carly; Gathright, Emily; Gilmore, Sarah; Derflinger, Bethany; Bennett, Brooke; Sterns, Anthony; Drew, Barbara L; Hughes, Joel W

    2015-01-01

    To determine if medication reminding via smartphone app increases adherence to antidepressant medications in college students. College students (N = 57) enrolled at a state-funded institution who had a current prescription for an antidepressant and regularly used a smartphone device. Participants were randomized to either a reminder group or a control group. Both groups were asked to complete a survey and undergo a manual pill count at the beginning of the study and 30 days later. There was a strong trend suggesting that the use of a medication reminder app was beneficial for adherence to antidepressant medication regimens. Factors influencing medication adherence in college students included health beliefs, use of illicit drugs, and type of professional care received. Use of a medication reminder may increase adherence to antidepressant medications in college students.

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

    Science.gov (United States)

    2014-08-01

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

  11. The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring

    Directory of Open Access Journals (Sweden)

    Soubry A

    2011-10-01

    Full Text Available Abstract In utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs of the imprinted Insulin-like Growth Factor 2 (IGF2 gene. Aberrant DNA methylation at the IGF2 and neighboring H19 DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436, as part of the Newborn Epigenetics Study (NEST. A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the H19 DMRs in newborns of African American (n = 177 but not Caucasian (n = 168 mothers who reported the use of antidepressive drugs during pregnancy (β = +6.89, p = 0.01. Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the IGF2 DMR (+3.05%, p = 0.01. In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the IGF2 DMRs in the offspring.

  12. Treatment of Fibromyalgia with Antidepressants

    Science.gov (United States)

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

    2000-01-01

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

  13. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Georg Anton Giæver Beiske

    2015-01-01

    Full Text Available Objective. Patients with multiple sclerosis (MS are often suffering from neuropathic pain. Antiepileptic drugs (AEDs and tricyclic antidepressants (TCAs are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females with mean age of 53 (±10 years and EDSS 4.8 (±1.7 used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6% or amitriptyline (9.7%. Polypharmacy was widespread (mean 5.4 drugs with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects.

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

    Science.gov (United States)

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

    2014-01-01

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

  15. [Antidepressive agents and suicidal tendencies].

    Science.gov (United States)

    Gründer, G; Veselinović, T; Paulzen, M

    2014-09-01

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

  16. Human experimental pain models: A review of standardized methods in drug development

    Directory of Open Access Journals (Sweden)

    K. Sunil kumar Reddy

    2012-01-01

    Full Text Available Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.

  17. Combination antidepressants - use by GPs and psychiatrists.

    Science.gov (United States)

    Horgan, David; Dodd, Seetal

    2011-06-01

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

  18. Antidepressants for chronic non-cancer pain in children and adolescents.

    Science.gov (United States)

    Cooper, Tess E; Heathcote, Lauren C; Clinch, Jacqui; Gold, Jeffrey I; Howard, Richard; Lord, Susan M; Schechter, Neil; Wood, Chantal; Wiffen, Philip J

    2017-08-05

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Antidepressants have been used in adults for pain relief and pain management since the 1970s. The clinical impression from extended use over many years is that antidepressants are useful for some neuropathic pain symptoms, and that effects on pain relief are divorced and different from effects on depression; for example, the effects of tricyclic antidepressants on pain may occur at different, and often lower, doses than those on depression. Amitriptyline is one of the most commonly used drugs for treating neuropathic pain in the UK. To assess the analgesic efficacy and adverse events of antidepressants used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. We searched the

  19. 78 FR 6762 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-01-31

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is announcing a public meeting to discuss the proposed rules to establish... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  20. 78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-02-13

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is providing public meeting registration information for two FSMA related... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  1. 77 FR 57055 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

    Science.gov (United States)

    2012-09-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I Regulatory New Drug Review: Solutions for..., 2012 (77 FR 48491). The document announced a meeting entitled ``Regulatory New Drug Review: Solutions...

  2. Prenatal Antidepressants and Autism Spectrum Disorder

    Science.gov (United States)

    2014-09-01

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

  3. 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

    . Nineteen trials of a range of newer antidepressants compared with placebo, containing 3335 participants, were included. The trials excluded young people at high risk of suicide and many co-morbid conditions and the participants are likely to be less unwell than those seen in clinical practice. We judged none of these trials to be at low risk of bias, with limited information about many aspects of risk of bias, high drop out rates and issues regarding measurement instruments and the clinical usefulness of outcomes, which were often variously defined across trials. Overall, there was evidence that those treated with an antidepressant had lower depression severity scores and higher rates of response/remission than those on placebo. However, the size of these effects was small with a reduction in depression symptoms of 3.51 on a scale from 17 to 113 (14 trials; N = 2490; MD -3.51; 95% confidence interval (CI) -4.55 to -2.47). Remission rates increased from 380 per 1000 to 448 per 1000 for those treated with an antidepressant. There was evidence of an increased risk (58%) of suicide-related outcome for those on antidepressants compared with a placebo (17 trials; N = 3229; RR 1.58; 95% CI 1.02 to 2.45). This equates to an increased risk in a group with a median baseline risk from 25 in 1000 to 40 in 1000. Where rates of adverse events were reported, this was higher for those prescribed an antidepressant. There was no evidence that the magnitude of intervention effects (compared with placebo) were modified by individual drug class. Caution is required in interpreting the results given the methodological limitations of the included trials in terms of internal and external validity. Further, the size and clinical meaningfulness of statistically significant results are uncertain. However, given the risks of untreated depression in terms of completed suicide and impacts on functioning, if a decision to use medication is agreed, then fluoxetine might be the medication of first choice

  4. Antidepressants and benzodiazepines for panic disorder in adults.

    Science.gov (United States)

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

    2016-09-12

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

  5. A review on antidepressant effect of medicinal plants

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2017-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Lara eKierlin

    2011-12-01

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

  7. Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis.

    Science.gov (United States)

    Xu, X-M; Yang, C; Liu, Y; Dong, M-X; Zou, D-Z; Wei, Y-D

    2017-08-01

    Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature. A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index. Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of -0.79 [95% confidence interval (CI) -1.13 to -0.45, P antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97-2.02; P = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05-2.89, P = 0.03). Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky. © 2017 EAN.

  8. Duloxetine versus other anti-depressive agents for depression

    Science.gov (United States)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  10. 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

  11. Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use

    DEFF Research Database (Denmark)

    Ytting, Henriette; Larsen, Fin Stolze

    2015-01-01

    here report the efficacy of everolimus treatment of patients with AIH. MATERIALS AND METHODS: Seven patients (six female, mean age 47 years, range 22-62 years) in whom disease control could not be achieved with standard therapy or the alternative drugs in use were included. RESULTS: Treatment...

  12. Standard drug concentrations and smart-pump technology reduce continuous-medication-infusion errors in pediatric patients.

    Science.gov (United States)

    Larsen, Gitte Y; Parker, Howard B; Cash, Jared; O'Connell, Mary; Grant, MaryJo C

    2005-07-01

    To determine if combining standard drug concentrations with "smart-pump" technology reduces reported medication-infusion errors. Preintervention and postintervention comparison of reported medication errors related to infusion therapies during the calendar years 2002 and 2003. A 242-bed university-affiliated tertiary pediatric hospital. Change in continuous-medication-infusion process, comprising the adoption of (1) standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered medication labels. Comparison of reported continuous-medication-infusion errors before and after the intervention. The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses. Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses. The use of standard drug concentrations, smart syringe pumps, and user-friendly labels reduces reported errors associated with continuous medication infusions. Standard drug concentrations can be chosen to allow most neonates to receive needed medications without concerns related to excess fluid administration.

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

    Directory of Open Access Journals (Sweden)

    Westergaard-Nielsen Niels

    2009-07-01

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

  14. The effect of anti-depressant Amitriptyline on the immune system

    Directory of Open Access Journals (Sweden)

    Dukan J

    1994-04-01

    Full Text Available We have studied the effect of amitriptyline, a tricyclic anti-depressant drug on several immune parameters of the Balb/c mice in order to evaluate its immunomodulatory effects. Results showed that amitriptyline will potentiates all of the immunocytes functions except for the production of PGE2 by LPS stimulated monocytes. We have also showed that amitriptyline can normalize the immunosuppressive effect of dexamethasone on mice (experimental stress. These results suggest that one of the mechanisms of action of the tricyclic anti-depressant drugs might be through the modulation of the immune system which has been suppressed by stress or distress

  15. Do patients initiate therapy? Primary non-adherence to statins and antidepressants in Iceland.

    Science.gov (United States)

    Thengilsdóttir, G; Pottegård, A; Linnet, K; Halldórsson, M; Almarsdóttir, A B; Gardarsdóttir, H

    2015-05-01

    Primary non-adherence occurs when a drug has been prescribed but the patient fails to have it dispensed at the pharmacy. To assess primary non-adherence to statins and antidepressants in Iceland, the association of demographic factors with primary non-adherence, and the time from when a prescription is issued until it is dispensed. Data on patients receiving a new prescription for a statin or an antidepressant from the Primary Health Care database were linked with dispensing histories from The Icelandic Prescription Database. The proportion of patients who did not have their prescription dispensed within a year from issuing (primary non-adherent) was assessed, as well as the time from issue until dispensing. Associations between demographic factors and primary non-adherence were estimated using logistic regression. The overall primary non-adherence was 6.3% and 8.0% for statins and antidepressants, respectively. The majority of patients had their prescription dispensed within 7 days (85% for statins, 87% for antidepressants). Being disabled and receiving a prescription for an expensive drug was associated with higher rates of primary non-adherence. The rate of primary non-adherence to statins and antidepressants in Iceland is low. Vulnerable groups such as the disabled should be given special attention when new drugs are prescribed. © 2015 John Wiley & Sons Ltd.

  16. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

    Directory of Open Access Journals (Sweden)

    João P. Costa-Nunes

    2015-01-01

    Full Text Available Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day and dicholine succinate (50 mg/kg/day, against standard antidepressants, imipramine (7 mg/kg/day and citalopram (15 mg/kg/day, utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.

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

    Science.gov (United States)

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

    2015-06-01

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

  18. The effects of drugs on nutrition

    African Journals Online (AJOL)

    to the oesophageal mucosa; failing hearing, vision, memory; and impaired mobility, which often leads to poor compliance or incorrect dosing. Drug–nutrient interactions are ... Anticholinergic drugs: atropine, oxybutynin, hyoscine, benztropine. Sedatives: diazepam, temasepam. Antidepressants and antipsychotic drugs.

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

    Science.gov (United States)

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

    2012-06-01

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

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

    African Journals Online (AJOL)

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

  1. Purely in silico BCS classification: science based quality standards for the world's drugs.

    Science.gov (United States)

    Dahan, Arik; Wolk, Omri; Kim, Young Hoon; Ramachandran, Chandrasekharan; Crippen, Gordon M; Takagi, Toshihide; Bermejo, Marival; Amidon, Gordon L

    2013-11-04

    BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs according to the BCS, using in silico methods. Three different in silico methods were examined: the well-established group contribution (CLogP) and atom contribution (ALogP) methods, and a new method based solely on the molecular formula and element contribution (KLogP). Metoprolol was used as the benchmark for the low/high permeability class boundary. Solubility was estimated in silico using a thermodynamic equation that relies on the partition coefficient and melting point. The validity of each method was affirmed by comparison to reference data and literature. We then used each method to provisionally classify the orally administered, IR drug products found in the WHO Model list of Essential Medicines, and the top-selling oral drug products in the United States (US), Great Britain (GB), Spain (ES), Israel (IL), Japan (JP), and South Korea (KR). A combined list of 363 drugs was compiled from the various lists, and 257 drugs were classified using the different in silico permeability methods and literature solubility data, as well as BDDCS classification. Lastly, we calculated the solubility values for 185 drugs from the combined set using in silico approach. Permeability classification with the different in silico methods was correct for 69-72.4% of the 29 reference drugs with known human jejunal permeability, and for 84.6-92.9% of the 14 FDA reference drugs in the set. The correlations (r(2)) between experimental log P values of 154 drugs and their CLogP, ALogP and KLogP were 0.97, 0.82 and 0.71, respectively. The different in silico permeability methods produced comparable results: 30-34% of the US, GB, ES and IL top selling drugs were class 1, 27-36.4% were class 2, 22-25.5% were class 3, and 5.46-14% were class 4 drugs, while ∼8% could not be classified. The WHO list

  2. Methodological Study to Develop Standard Operational Protocol on Intramuscular (IM, Intradermal (ID and Subcutaneous Drug Administration for Children

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Bijarania

    2017-10-01

    Full Text Available Introduction: Medicine administration is a major role played by registered nurses. Medicines are prescribed by the physician and dispensed by the pharmacist but responsibility for meticulous administration rests with the registered nurse. It becomes even more important when drugs are to be administered to children. Drug administration via Intramuscular (IM, Intradermal (ID and Subcutaneous route is a complex process. Errors are associated with medicine administration. Aim: The objective of this study was to develop Standard Operational Protocol (SOP for IM, ID and Subcutaneous drug administration and checklist to assess the implementation of the developed SOP. Materials and Methods: A methodological research design adapted to carry out the present study to develop standard operational protocol for IM, ID and subcutaneous drug administration for children, admitted in Advanced Paediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study included 58 bedside nurses and 90 observations of medicine administration procedure. Results: The Content Validity Index (CVI was prepared to assess the validity of content (items of SOPs and checklists. Over all Cronbach's-alpha values was calculated to assess the internal consistency of Items in SOPs and checklists. CVI of SOP and checklists were 98.51%, 97.83% and 99.03%. Over all Cronbach'salpha values were calculated 0.96, 0.82 and 0.95. All the nurses felt that SOPs are useful. Conclusion: Valid and feasible SOPs for drug administration in children along with valid and reliable checklists were developed. It is recommended to use this document for drug administration in children to prevent any possible error during drug administration to children.

  3. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  4. 78 FR 42084 - Electronic Study Data Submission; Data Standard Support; Availability of the Center for Drug...

    Science.gov (United States)

    2013-07-15

    ... commitment to the development, implementation, and maintenance of a comprehensive data standards program to facilitate the efficient and effective review of regulatory submissions so that safe and effective products... Innovation Act. The CDER Data Standards Strategy supersedes version 1.1 of the CDER Data Standards Plan...

  5. Drug treatment for myotonia (Review)

    NARCIS (Netherlands)

    Trip, J.; Drost, G.; Engelen, B.G.M. van; Faber, C.G.

    2006-01-01

    BACKGROUND: Abnormal delayed relaxation of skeletal muscles, known as myotonia, can cause disability in myotonic disorders. Sodium channel blockers, tricyclic antidepressive drugs, benzodiazepines, calcium-antagonists, taurine and prednisone may be of use in reducing myotonia. OBJECTIVES: To

  6. Drug: D07623 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 01942 ... Iminobenzyl antipsychotic Chemical group: DG01312 ... Tricyclic antidepressant, Iminodibenzyl derivativ... D07623 Drug Carpipramine (INN) ... C28H38N4O D07623.gif ... Neuropsychiatric agent ... DG

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

    Science.gov (United States)

    Uzbay, I Tayfun

    2008-01-01

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

  8. Depression, antidepressants, and sexual function.

    Science.gov (United States)

    Victor, B S

    1995-08-01

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

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

    Science.gov (United States)

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

    2006-10-01

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

  10. Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice.

    Science.gov (United States)

    Bourin, Michel; Chenu, Franck; Prica, Corina; Hascoët, Martine

    2009-09-01

    A deficiency in brain monoamine systems (serotonin, dopamine, and/or norepinephrine) have long been hypothesized for the pathogenesis of depression. Drugs enhancing neurotransmission of those monoamines have been proven to have antidepressant effects. We hypothesized that aripiprazole, a partial D(2) agonist, could increase the activity of various antidepressants in the mice forced swimming test (FST), an animal model of depression. The scope of this study was to investigate the antidepressant-like effect of aripiprazole, when combined with conventional antidepressants drugs. This study assessed the effects of co-administration of aripiprazole with selective serotonin reuptake inhibitors (SSRIs; sertraline, paroxetine, and citalopram), selective serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine and minalcipran), selective norepinephrine reuptake inhibitor (NRI; desipramine), and the dual dopamine and norepinephrine reuptake inhibitor (bupropion), using the FST in mice. Subactive doses of aripiprazole and antidepressants sertraline, paroxetine, citalopram, venlafaxine, minalcipran, bupropion (4 and 8 mg/kg), and desipramine (2 and 4 mg/kg) were given i.p. 30 and 45 min, respectively, before the test. Aripiprazole (0.03 and 0.06 mg/kg) combined with inactive doses of antidepressants, increased the activity of all antidepressants with the exception of bupropion and desipramine. The augmentation effects of aripiprazole, in the present study, are in agreement with clinical evidence suggesting that aripiprazole may enhance the efficacy of therapeutic effect of SSRIs and SNRIs but not of NRI. These results suggest that augmentation effect of aripiprazole only appears when 5-HT system is activated and might implicate complex regulation between dopamine and 5-HT(1A) and 5-HT(2A) receptors.

  11. Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels.

    Science.gov (United States)

    Sales, Amanda Juliana; Joca, Sâmia Regiane Lourenço

    2016-02-01

    Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressant-like effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated. Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants). Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1 mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT. These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression.

  12. Licensing of psychoactive drugs in the Netherlands.

    Science.gov (United States)

    ten Ham, M

    1983-06-01

    The Dutch Board for the Evaluation of Medicines approves applications for a marketing authorization if on the basis of pharmaceutical, pharmacological--toxicological, and clinical data the benefit--risk balance is considered positive. In the Netherlands, almost 4000 drugs have a marketing authorization, 145 of these belonging to the psychotropic drugs. During the Board's existence the number of applications and the number of approvals for antipsychotics and antidepressants decreased, while an increasing amount of anxiolytics was applied for and approved. This phenomenon may reflect the prescribing behavior of doctors. The Board has on several occasions actively influenced the market situation of certain drugs, e.g., amphetamines have almost totally disappeared from the market since a strong restriction of the indications was imposed. A certain shift in the evaluation policy of the Board can be noticed in some respects, for instance, data on chronic use are no longer required for registration of hypnotics. The requirements for registration of antidepressants are less strict than in the past. The Board tries by its registration policy to be an objective interface between the drug-producing companies and the consumer, the patient, and seeks the highest standards possible in the drug market.

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

    Science.gov (United States)

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

    2014-08-01

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

  14. Physicochemical and elemental studies of Hydrocotyle javanica Thunb. for standardization as herbal drug

    Directory of Open Access Journals (Sweden)

    Manab Mandal

    2017-11-01

    Conclusions: Hence the present physicochemical and elements studies reveals that the plant Hydrocotyle javanica Thunb. could be a potent source of herbal preparation as well as a safe and novel synthetic antibacterial drug.

  15. The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review.

    Science.gov (United States)

    Kolla, Bhanu Prakash; Mansukhani, Meghna P; Bostwick, J Michael

    2018-04-01

    Restless legs syndrome is commonly co-morbid with medical conditions that are treated with antidepressant medications, such as depression, anxiety, fibromyalgia, and chronic insomnia disorder. Evidence from case reports and cross-sectional studies suggests that antidepressants may induce or worsen restless legs syndrome and increase periodic limb movements. We undertook a systematic review of the literature to identify and collate all prospective studies that measured restless legs syndrome symptoms and/or periodic limb movements following the introduction of an antidepressant. Eighteen studies were eligible for inclusion. Current data indicate that onset or exacerbation of restless legs syndrome and rise in frequency of periodic limb movements are uncommon following the initiation of an antidepressant. Among the various antidepressants, mirtazapine may be associated with higher rates of restless legs syndrome and periodic limb movements. One small study of normal volunteers suggested that venlafaxine may be associated with an increase in restless legs syndrome symptoms and periodic limb movements. Sertraline, fluoxetine, and amitriptyline appear to increase periodic limb movements that do not disrupt sleep and are thus unlikely to be clinically significant. On the other hand, bupropion may reduce restless legs syndrome symptoms, at least in the short term. Sedating antidepressants such as trazodone, nefazodone, and doxepin do not seem to aggravate periodic limb movements. The current evidence is limited by poor study design, inadequate use of standardized questionnaires, and heterogeneous populations studied for variable lengths of time. Future research should attempt to remedy these shortcomings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine.

    Science.gov (United States)

    Gibbons, Robert D; Brown, C Hendricks; Hur, Kwan; Davis, John; Mann, J John

    2012-06-01

    The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults. To determine the short-term safety of antidepressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. All intent-to-treat person-level longitudinal data of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. The suicide items from the Children's Depression Rating Scale-Revised and the Hamilton Depression Rating Scale as well as adverse event reports of suicide attempts and suicide during active treatment were analyzed in 9185 patients (fluoxetine: 2635 adults, 960 geriatric patients, 708 youths; venlafaxine: 2421 adults with immediate-release venlafaxine and 2461 adults with extended-release venlafaxine) for a total of 53 260 person-week observations. Suicidal thoughts and behavior decreased over time for adult and geriatric patients randomized to fluoxetine or venlafaxine compared with placebo, but no differences were found for youths. In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior. Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the

  17. 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.

  18. Effect of antidepressants on neuroendocrine axis in humans.

    Science.gov (United States)

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

    1982-01-01

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

  19. Adjustment for reporting bias in network meta-analysis of antidepressant trials

    Directory of Open Access Journals (Sweden)

    Trinquart Ludovic

    2012-09-01

    Full Text Available Abstract Background Network meta-analysis (NMA, a generalization of conventional MA, allows for assessing the relative effectiveness of multiple interventions. Reporting bias is a major threat to the validity of MA and NMA. Numerous methods are available to assess the robustness of MA results to reporting bias. We aimed to extend such methods to NMA. Methods We introduced 2 adjustment models for Bayesian NMA. First, we extended a meta-regression model that allows the effect size to depend on its standard error. Second, we used a selection model that estimates the propensity of trial results being published and in which trials with lower propensity are weighted up in the NMA model. Both models rely on the assumption that biases are exchangeable across the network. We applied the models to 2 networks of placebo-controlled trials of 12 antidepressants, with 74 trials in the US Food and Drug Administration (FDA database but only 51 with published results. NMA and adjustment models were used to estimate the effects of the 12 drugs relative to placebo, the 66 effect sizes for all possible pair-wise comparisons between drugs, probabilities of being the best drug and ranking of drugs. We compared the results from the 2 adjustment models applied to published data and NMAs of published data and NMAs of FDA data, considered as representing the totality of the data. Results Both adjustment models showed reduced estimated effects for the 12 drugs relative to the placebo as compared with NMA of published data. Pair-wise effect sizes between drugs, probabilities of being the best drug and ranking of drugs were modified. Estimated drug effects relative to the placebo from both adjustment models were corrected (i.e., similar to those from NMA of FDA data for some drugs but not others, which resulted in differences in pair-wise effect sizes between drugs and ranking. Conclusions In this case study, adjustment models showed that NMA of published data was not

  20. Severe potential drug-drug interactions in older adults with dementia and associated factors

    Directory of Open Access Journals (Sweden)

    Michele Bogetti-Salazar

    2016-01-01

    Full Text Available OBJECTIVE: To identify the main severe potential drug-drug interactions in older adults with dementia and to examine the factors associated with these interactions. METHOD: This was a cross-sectional study. The enrolled patients were selected from six geriatrics clinics of tertiary care hospitals across Mexico City. The patients had received a clinical diagnosis of dementia based on the current standards and were further divided into the following two groups: those with severe drug-drug interactions (contraindicated/severe (n=64 and those with non-severe drug-drug interactions (moderate/minor/absent (n=117. Additional socio-demographic, clinical and caregiver data were included. Potential drug-drug interactions were identified using Micromedex Drug Reax 2.0® database. RESULTS: A total of 181 patients were enrolled, including 57 men (31.5% and 124 women (68.5% with a mean age of 80.11±8.28 years. One hundred and seven (59.1% patients in our population had potential drug-drug interactions, of which 64 (59.81% were severe/contraindicated. The main severe potential drug-drug interactions were caused by the combinations citalopram/anti-platelet (11.6%, clopidogrel/omeprazole (6.1%, and clopidogrel/aspirin (5.5%. Depression, the use of a higher number of medications, dementia severity and caregiver burden were the most significant factors associated with severe potential drug-drug interactions. CONCLUSIONS: Older people with dementia experience many severe potential drug-drug interactions. Anti-depressants, antiplatelets, anti-psychotics and omeprazole were the drugs most commonly involved in these interactions. Despite their frequent use, anti-dementia drugs were not involved in severe potential drug-drug interactions. The number and type of medications taken, dementia severity and depression in patients in addition to caregiver burden should be considered to avoid possible drug interactions in this population.

  1. Relabeling the Medications We Call Antidepressants

    Directory of Open Access Journals (Sweden)

    David Antonuccio

    2012-01-01

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

  2. Accelerated antidepressant response to lithium augmentation of imipramine

    Directory of Open Access Journals (Sweden)

    Rajiv Saini

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  5. Antidepressant medication use and breast cancer risk.

    Science.gov (United States)

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

    2009-04-01

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

  6. Standard-based comprehensive detection of adverse drug reaction signals from nursing statements and laboratory results in electronic health records.

    Science.gov (United States)

    Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han

    2017-07-01

    We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n   = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation. © The Author 2017. Published by Oxford University Press on behalf of the American

  7. Anti-convulsants and anti-depressants.

    Science.gov (United States)

    Dickenson, A H; Ghandehari, J

    2007-01-01

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

  8. Robust and Sustained Effect of Ketamine Infusions Coadministered with Conventional Antidepressants in a Patient with Refractory Major Depression

    Directory of Open Access Journals (Sweden)

    José Manuel Montes

    2015-01-01

    Full Text Available Antidepressant treatments show low capacity to achieve full clinical remissions. Electroconvulsive therapy is an alternative treatment which has been shown to be more effective but it is not well tolerated and there are concerns regarding its safety. We present the case of a patient with resistant depression and modest and transient response to ECT and who showed a robust and maintained response after six i.v. ketamine (0.5 mg/kg infusions without withdrawing her antidepressant regimen. Ketamine was very well tolerated. This case illustrates the potential role of ketamine as a booster to standard antidepressants.

  9. 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...

  10. The impact of direct-to-consumer television and magazine advertising on antidepressant use.

    Science.gov (United States)

    Avery, Rosemary J; Eisenberg, Matthew D; Simon, Kosali I

    2012-09-01

    We examine whether exposure to direct-to-consumer advertising (DTCA) for antidepressant drugs affects individual use of these medications among those suffering from depression. Prior studies have almost exclusively relied on making connections between national or market-level advertising volume/expenditures and national or individual-level usage of medications. This is the first study to: estimate the impact of individual-level exposure to DTCA on individual-level use of antidepressants; estimate the impact of individual-level exposure to television DTCA on individual-level use in any drug class; consider the relative and interactive impact of DTCA in two different media in any drug class; and, consider the heterogeneity of impact among different populations in an econometric framework in the antidepressant market. There are also important limitations to note. Unlike prior market level studies that use monthly data, we are limited to aggregated annual data. Our measures of potential advertising exposure are constructed assuming that media consumption patterns are stable during the year. We are also not able to study the impact of advertising on use of antidepressants for conditions other than depression, such as anxiety disorders. We find that: DTCA impacts antidepressant use in a statistically and economically significant manner; that these effects are present in both television and magazine advertising exposure but do not appear to have interactive effects; are stronger for women than for men in the magazine medium, but are about equally strong for men and women in the TV medium; and, are somewhat stronger for groups suffering from more severe forms of depression. The overall size of the effect is a 6-10 percentage point increase in antidepressant use from being exposed to television advertising; the corresponding magazine effects are between 3 and 4 percentage points. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Bundgaard, Kristian; Hansen, Steen M; Mortensen, Rikke Nørmark

    2017-01-01

    AIM: 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. METHODS: We included all......,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...

  12. Antidepressant use and risk of adverse outcomes in people aged 20-64 years: cohort study using a primary care database.

    Science.gov (United States)

    Coupland, Carol; Hill, Trevor; Morriss, Richard; Moore, Michael; Arthur, Antony; Hippisley-Cox, Julia

    2018-03-08

    Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20-64 years diagnosed with depression. We conducted a cohort study in 238,963 patients aged 20-64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables. During 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21-1.39) and other antidepressants (1.28, 1.11-1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25-1.88) and other antidepressants (1.61, 1.22-2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22-1.59) and other antidepressants (1.26, 1.08-1.47) than for selective serotonin reuptake inhibitors over 5 years

  13. Clinical trials information in drug development and regulation : existing systems and standards

    NARCIS (Netherlands)

    Valkenhoef, Gert van; Tervonen, Tommi; Brock, Bert de; Hillege, Hans

    2012-01-01

    Clinical trials provide pivotal evidence on drug efficacy and safety. The evidence, information from clinical trials, is currently used by regulatory decision makers in marketing authorization decisions, but only in an implicit manner. For clinical trials information to be used in a transparent and

  14. Prevalence, incidence, indication, and choice of antidepressants in patients with and without chronic kidney disease: a matched cohort study in UK Clinical Practice Research Datalink.

    Science.gov (United States)

    Iwagami, Masao; Tomlinson, Laurie A; Mansfield, Kathryn E; McDonald, Helen I; Smeeth, Liam; Nitsch, Dorothea

    2017-07-01

    People with chronic kidney disease (CKD) have an increased prevalence of depression, anxiety, and neuropathic pain. We examined prevalence, incidence, indication for, and choice of antidepressants among patients with and without CKD. Using the UK Clinical Practice Research Datalink, we identified patients with CKD (two measurements of estimated glomerular filtration rate antidepressant prescribing in the six months prior to index date (prevalence), the first prescription after index date among non-prevalent users (incidence), and recorded diagnoses (indication). We compared antidepressant choice between patients with and without CKD among patients with a diagnosis of depression. There were 242 349 matched patients (median age 76 [interquartile range 70-82], male 39.3%) with and without CKD. Prevalence of antidepressant prescribing was 16.3 and 11.9%, and incidence was 57.2 and 42.4/1000 person-years, in patients with and without CKD, respectively. After adjusting for confounders, CKD remained associated with higher prevalence and incidence of antidepressant prescription. Regardless of CKD status, selective serotonin reuptake inhibitors were predominantly prescribed for depression or anxiety, while tricyclic antidepressants were prescribed for neuropathic pain or other reasons. Antidepressant choice was similar in depressed patients with and without CKD. The rate of antidepressant prescribing was nearly one and a half times higher among people with CKD than in the general population. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  15. Agomelatine versus other antidepressive agents for major depression.

    Science.gov (United States)

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

    2013-12-17

    Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated with a sad or depressed mood, a reduced capacity to feel pleasure, feelings of hopelessness, loss of energy, altered sleep patterns, weight fluctuations, difficulty in concentrating and suicidal ideation. There is a need for more effective and better tolerated antidepressants to combat this condition. Agomelatine was recently added to the list of available antidepressant drugs; it is a novel antidepressant that works on melatonergic (MT1 and MT2), 5-HT 2B and 5-HT2C receptors. Because the mechanism of action is claimed to be novel, it may provide a useful, alternative pharmacological strategy to existing antidepressant drugs. The objective of this review was 1) to determine the efficacy of agomelatine in alleviating acute symptoms of major depressive disorder in comparison with other antidepressants, 2) to review the acceptability of agomelatine in comparison with other antidepressant drugs, and, 3) to investigate the adverse effects of agomelatine, including the general prevalence of side effects in adults. We searched the Cochrane Collaboration's Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 31 July 2013. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 onwards), MEDLINE (1950 onwards) and PsycINFO (1967 onwards). We checked reference lists of relevant studies together with reviews and regulatory agency reports. No restrictions on date, language or publication status were applied to the search. Servier Laboratories (developers of agomelatine) and other experts in the field were contacted for supplemental data. Randomised controlled trials allocating adult participants with major depression to agomelatine versus any

  16. The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents.

    Science.gov (United States)

    Tucker, J C; File, S E

    1986-01-01

    With the exception of amineptin, buproprion and nomifensine all tricyclic and 'atypical' antidepressants have been reported to reduce spontaneous motor activity in rodents, after both acute and chronic administration. However, with the diversity of chemical actions of these drugs it is unlikely that a single neurochemical mechanism is underlying this one behavioral effect. These widespread sedative effects have implications for interpreting behavioral changes in other test situations, since sedation generally occurs at doses that fall within the dose-range effective in other tests. We also review the effects on spontaneous motor activity of withdrawal from chronic antidepressant treatment.

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

    Science.gov (United States)

    Gibson, Kerry; Cartwright, Claire; Read, John

    2016-05-11

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

  18. 77 FR 48491 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

    Science.gov (United States)

    2012-08-14

    ... many years, it is not an extensible modern technology. Moreover, it is not supported and maintained by..., structured documents and Clinical Data Architecture) be a viable study data exchange standard? Please explain...

  19. [Actuality investigation on general crude drugs and its quality standard of Tibetan medicine].

    Science.gov (United States)

    Zhong, Guoyue; Zhou, Fucheng; Shi, Shangmei; Zhou, Huarong; Yu, Jiangyong; Ping, A; Liu, Haiqing; Dawa, Zhuoma

    2012-08-01

    To provide a reference for the standardization of Tibetan medicine. Investigating the hospital preparations , Tibetan formulated products, and the literature recorded preparations in the Tibetan, Qinghai, Gansu, Sichuan and Yunnan Provinces. Moreover, the varieties, original bases and standard conditions of these preparations were analyzed. According to Chinese Pharmacopoeia, Tibetan medicine part of ministerial standard, Tibetan medicine standards and related monographs and literatures of Tibetan medicine. About 502 various of herbs were used in 711 hospital preparations from 40 medical institutions, Tibetan formulated products from Tibetan pharmaceutical factories, and 439 literature recorded preparations. About 154 herbs were used in more than 10 preparations, while most of them were Tibetan endemic species. About 416 medicinal varieties have the original documented basis, including 287 botanicals, 78 animal medicines, 51 mineral medicines, involving a total of 94 families, 261 genus and 643 species of botanical origin (including species of the next grade), 35 families, 52 genera and 61 species of the animal origin (including species of the next grade). About 122 varieties of herbs were cross-used in the traditional Chinese medicine and Tibetan medicine, about 80% of Tibetan medicinal varieties are produced in the Tibetan Areas of Tibet Plateau. About 293 medicinal varieties were contained in the above standards. Most of the herb's standards only contains character, indentification, and examination, except for 8 varieties which were recorded in the Chinese Pharmacopoeia (2010) as Tibetan medicine. This study of quality standard of Tibetan medicine should have an emphasis on the general varieties, especially the study on the arrangement research and the efficacious material basis of the varieties and the original, as well as term standardization of the National Medicine.

  20. Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study.

    Science.gov (United States)

    Amsterdam, Jay D; Shults, Justine; Soeller, Irene; Mao, Jun James; Rockwell, Kenneth; Newberg, Andrew B

    2012-01-01

    Anxiety and depression are the most commonly reported psychiatric conditions and frequently occur as comorbid disorders. While the advent of conventional drug therapies has simplified treatment, a large segment of the population goes untreated or declines conventional therapy for financial, cultural, or personal reasons. Therefore, the identification of inexpensive and effective alternative therapies for anxiety and depression is of relevance to public health. The current study explores data from a 2009 clinical chamomile trial in humans to determine if chamomile provides clinically meaningful antidepressant activity versus a placebo. In the 2009 randomized, double-blind, placebo-controlled study, the research team examined the antianxiety and antidepressant action of oral chamomile (Matricaria recutita) extract in participants with symptoms of comorbid anxiety and depression. In the 2009 study, all of participants' evaluations took place at the Depression Research Unit at the University of Pennsylvania. The study drew participants from patients at the Department of Family Medicine and Community Health's primary care clinic at the University of Pennsylvania, Philadelphia. Of the 57 participants in the 2009 trial, 19 had anxiety with comorbid depression; 16 had anxiety with a past history of depression; and 22 had anxiety with no current or past depression. The intervention and placebo groups in the 2009 trial received identically appearing 220-mg capsules containing either pharmaceutical-grade chamomile extract standardized to a content of 1.2% apigenin or a placebo (ie, lactose monohydrate NF), respectively. In the current study, the research team used generalized estimating equations analysis to identify clinically meaningful changes over time in scores from the Hamilton Depression Rating (HAM-D) questionnaire among treatment groups. In the current study, the research team observed a significantly greater reduction over time in total HAM-D scores for chamomile vs

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

    Science.gov (United States)

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

    2009-10-01

    Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

  2. Antidepressants and risk of cataract development: A population-based, nested case-control study.

    Science.gov (United States)

    Chou, Po-Han; Chu, Che-Sheng; Chen, Yi-Huei; Hsu, Min-Yen; Huang, Min-Wei; Lan, Tsuo-Hung; Lin, Ching-Heng

    2017-06-01

    Previous studies demonstrated increased risk of cataract development among users of selective serotonin reuptake inhibitors (SSRIs). However, it remains unknown whether this risk also prevails with the use of other types of antidepressants. The aim of this study was to investigate whether use of antidepressants is associated with an increased risk of cataract development. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of antidepressant and the risk of cataracts is examined. We conducted a nested case-control study using National Health Insurance Research Database in Taiwan. A total of 14,288 patients were included; 7651 in the cataract group and 6637 in the control group. Antidepressant exposure was categorized by type, duration of use, and binding affinities of SERT. The association between antidepressant exposure and cataract development was assessed using conditional logistic regression analysis. The adjusted odds ratios (AORs) for developing cataracts among continuous users of SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other antidepressants were 1.26 (95% confidence interval (CI): 1.12-1.41, pantidepressants with intermediate SERT binding affinities (AOR: 1.68; 95% CI: 1.10-2.56, p=0.017) were significantly associated with increased risks of cataract development. Several confounding factors such as obesity, multiple drug users, family history of cataracts, substance use, and environmental factors (such as sunlight or radiation exposure) were acquired. We found increased risk of cataract development in patients continuously using antidepressants. Regular ocular evaluations in these patients are warranted. Copyright © 2017. Published by Elsevier B.V.

  3. Beliefs of people taking antidepressants about causes of depression and reasons for increased prescribing rates.

    Science.gov (United States)

    Read, John; Cartwright, Claire; Gibson, Kerry; Shiels, Christopher; Haslam, Nicholas

    2014-10-01

    Public beliefs about the causes of mental health problems are related to desire for distance and pessimism about recovery, and are therefore frequently studied. The beliefs of people receiving treatment are researched less often. An online survey on causal beliefs about depression and experiences with antidepressants was completed by 1829 New Zealand adults prescribed anti-depressants in the preceding five years, 97.4% of whom proceeded to take antidepressants. The most frequently endorsed of 17 causal beliefs were family stress, relationship problems, loss of loved one, financial problems, isolation, and abuse or neglect in childhood. Factor analysis produced three factors: 'bio-genetic', 'adulthood stress' and 'childhood adversity'. The most strongly endorsed explanations for increases in antidepressant prescribing invoked improved identification, reduced stigma and drug company marketing. The least strongly endorsed was 'Anti-depressants are the best treatment'. Regression analyses revealed that self-reported efficacy of the antidepressants was positively associated with bio-genetic causal beliefs, negatively associated with childhood adversity beliefs and unrelated to adulthood stress beliefs. The belief that 'People cannot׳ get better by themselves even if they try' was positively associated with bio-genetic beliefs. The convenience sample may have been biased towards a favourable view of bio-genetic explanations, since 83% reported that the medication reduced their depression. Clinicians׳ should consider exploring patients׳ causal beliefs. The public, even when taking antidepressants, continues to hold a multi-factorial causal model of depression with a primary emphasis on psycho-social causes. A three factor model of those beliefs may lead to more sophisticated understandings of relationships with stigma variables. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice.

    Science.gov (United States)

    Abdel-Wahab, Basel A; Salama, Ragaa H

    2011-11-01

    Venlafaxine (VLF) is an approved antidepressant that is claimed to have superior clinical efficacy to comparable drugs. Recently, many studies showed the relationship between depression and increased oxidative stress. This study investigated the relationship between the antidepressant effect of VLF and its ability to protect animals against stress-induced oxidative lipid peroxidation and DNA damage induced during antidepressant testing. The antidepressant effect of long-term treatment (21 days) of VLF in doses 5, 10 and 20mg/kg/day, i.p. was tested using forced swimming test (FST) and tail suspension test (TST). The effects of VLF on hippocampal lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH), total antioxidant (TAC) levels and glutathione-S-transferase (GST) activity were tested. Furthermore, the corresponding changes in serum and hippocampal 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. Long-term VLF treatment showed a significant, antidepressant effect in both FST and TST. VLF could decrease the hippocampal MDA and NO and to increase hippocampal GSH and TAC levels and GST activity in the tested animals. Only GSH and TAC levels were increased by VLF in the non-tested animals. In addition, both serum and hippocampal 8-OHdG levels were significantly reduced by VLF in animals exposed to antidepressant tests. Long-term VLF treatment in the effective antidepressant doses can protect against stress-induced oxidative cellular and DNA damage. This action may be through antagonizing the oxidative stress and enhancing the antioxidant defense mechanisms. Consequently, pharmacological modulation of stress-induced oxidative DNA damage as a possible stress-management approach should be an important avenue of further research. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Elevated risk of preeclampsia in pregnant women with depression: depression or antidepressants?

    Science.gov (United States)

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

    2012-05-15

    A previous study suggested an increased risk of preeclampsia among women treated with selective serotonin reuptake inhibitors (SSRIs). Using population-based health-care utilization databases from British Columbia (1997-2006), the authors conducted a study of 69,448 pregnancies in women with depression. They compared risk of preeclampsia in women using SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) between gestational weeks 10 and 20 with risk in depressed women not using antidepressants. Among prepregnancy antidepressant users, the authors compared the risk in women who continued antidepressants between gestational weeks 10 and 24 with the risk in those who discontinued. Relative risks and 95% confidence intervals were estimated. The risk of preeclampsia in depressed women not treated with antidepressants (2.4%) was similar to that in women without depression (2.3%). Compared with women with untreated depression, women treated with SSRI, SNRI, and TCA monotherapy had adjusted relative risks of 1.22 (95% confidence interval (CI): 0.97, 1.54), 1.95 (95% CI: 1.25, 3.03), and 3.23 (95% CI: 1.87, 5.59), respectively. Within prepregnancy antidepressant users, the relative risk for preeclampsia among continuers compared with discontinuers was 1.32 (95% CI: 0.95, 1.84) for SSRI, 3.43 (95% CI: 1.77, 6.65) for SNRI, and 3.26 (95% CI: 1.04, 10.24) for TCA monotherapy. Study results suggest that women who use antidepressants during pregnancy, especially SNRIs and TCAs, have an elevated risk of preeclampsia. These associations may reflect drug effects or more severe depression.

  6. Capgras syndrome responding to the antidepressant mirtazapine.

    Science.gov (United States)

    Khouzam, Hani Raoul

    2002-01-01

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

  7. Antidepressants: MedlinePlus Health Topic

    Science.gov (United States)

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

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

    Science.gov (United States)

    Jirón, Marcela; Machado, Márcio; Ruiz, Inés

    2008-09-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

  10. 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

  11. Reliability of in vitro and in vivo methods for predicting P-glycoprotein effect on antidepressants delivery to the brain

    Science.gov (United States)

    Zheng, Yi; Chen, Xijing; Benet, Leslie Z.

    2017-01-01

    As P-glycoprotein (P-gp) transport on antidepressant delivery has been extensively evaluated using in vitro cellular and in vivo rodent models, an increasing number of publications addressed the effect of P-gp in limiting brain penetration of antidepressants and causing treatment-resistant depression in current clinical therapies. However, contradictory results were observed in different systems. It is of vital importance to understand the potential for drug interactions related to P-gp at the blood-brain barrier (BBB), and whether co-administration of a P-gp inhibitor together with an antidepressant is a good clinical strategy for dosing of patients with treatment-resistant depression. In this review, the complicated construction of the BBB, the transport mechanisms for compounds that cross the BBB, and the basic characteristics of antidepressants are illustrated. Further, the reliability of different systems related to antidepressant brain delivery, including in vitro bidirectional transport cell lines, in vivo Mdr1 knock-out mice, and chemical inhibition studies in rodents are analyzed, supporting a low possibility that P-gp affects currently marketed antidepressants when these results are extrapolated to human BBB. These findings can also be applied to other central nervous system drugs. PMID:26293617

  12. Anti-Nociceptive Effect of Tricyclic Anti-Depressants Following Intrathecal Administration

    Science.gov (United States)

    Kehl, Lois J.; Wilcox, George L.

    1984-01-01

    The anti-nociceptive effects of three tricyclic anti-depressants (desipramine, protriptyline, fluoxetine) were evaluated in mice following intrathecal administration. Nociceptive behavior was produced by intrathecal administration of Substance P and measured for 60 seconds following subcutaneous and intrathecal administration of vehicle and increasing doses of the drugs being tested. Systemically administered protriptyline produced dose related antinociception in this paradigm. A similar effect was seen following systemic desipramine; while fluoxetine was inactive systemically. Both protriptyline and desipramine given intrathecally were antinociceptive while fluoxetine had a biphasic effect, being analgesic only at low doses. These results indicate that tricyclic antidepressants may produce analgesia at the spinal level in rodents. This action may be related to the therapeutic success of tricyclic antidepressants in chronic pain syndromes. PMID:6335632

  13. Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice

    Directory of Open Access Journals (Sweden)

    Usama Karama

    2016-01-01

    Full Text Available The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl-N-methylmethanamine (5 and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl-N-methylmethanamine (6 as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3 and (4 were successfully synthesized via a [4 + 2] cycloaddition between acrolein and 1,8-dichloroanthracene. The synthesized compounds were investigated for antidepressant activity using the forced swimming test. Compounds (5, (6 and (3 showed significant reduction in the mice immobility indicating significant antidepressant effects. These compounds significantly reduced the immobility times at a dose 80 mg/kg by 84.0%, 86.7% and 71.1% respectively.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    a 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...... of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of > or = 18 and/or a Hamilton subscale score of > or = 9. Diagnostic classification...... according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had...

  15. Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus.

    Science.gov (United States)

    Nishioka, G; Yamada, M; Kudo, K; Takahashi, K; Kiuchi, Y; Higuchi, T; Momose, K; Kamijima, K; Yamada, M

    2003-03-01

    It has been proposed that signaling pathways involved in adaptive neural plasticity are long-term targets for the action of electroconvulsive treatment (ECT), which is widely used in the treatment of drug-resistant depression. We have previously performed EST analysis to identify some molecular machinery responsible for antidepressant effect. One of the cDNA fragments identified as antidepressant related genes/ESTs was identified as kf-1 which has a RING-H2 finger motif at the carboxy-terminus. In the present study, we have demonstrated the induction of kf-1 in rat frontal cortex and hippocampus not only after chronic antidepressant treatment, but also after a single and repeated ECT. RING finger proteins are proposed to play some important roles in the ubiquitin-proteasome system. In conclusion, the current investigation has identified kf-1 as a novel molecular target for antidepressants and ECT.

  16. Pharmacogenetics of antidepressant response: An update

    Directory of Open Access Journals (Sweden)

    Drago Antonio

    2009-04-01

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

  17. Reevaluating Antidepressant Selection in Patients With Bruxism and Temporomandibular Joint Disorder.

    Science.gov (United States)

    Rajan, Royce; Sun, Ye-Ming

    2017-05-01

    Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to several conditions affecting the temporomandibular joint of the jaw and the muscles of mastication. As with most pain disorders, a high prevalence of depression and anxiety is associated with TMD. Research has shown that selective serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major depressive disorder, may not be suitable for TMD patients because SSRIs can induce teeth-grinding, otherwise known as bruxism. This is problematic because bruxism is believed to further exacerbate TMD. Therefore, the purpose of this literature review is to better understand the mechanism of SSRI-induced bruxism, as well as discuss alternative antidepressant options for treating depression and anxiety in patients with bruxism and TMD. Alternative classes of antidepressants reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors. Findings indicate that dopamine agonists and buspirone are currently the most effective medications to treat the side effects of SSRI-induced bruxism, but results regarding the effectiveness of specific antidepressants that avoid bruxism altogether remain inconclusive.

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

    Science.gov (United States)

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

    2017-07-10

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

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

    Directory of Open Access Journals (Sweden)

    Paul R Albert

    2010-06-01

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

  20. Stopping Antidepressants and Anxiolytics as Major Concerns Reported in Online Health Communities: A Text Mining Approach.

    Science.gov (United States)

    Abbe, Adeline; Falissard, Bruno

    2017-10-23

    Internet is a particularly dynamic way to quickly capture the perceptions of a population in real time. Complementary to traditional face-to-face communication, online social networks help patients to improve self-esteem and self-help. The aim of this study was to use text mining on material from an online forum exploring patients' concerns about treatment (antidepressants and anxiolytics). Concerns about treatment were collected from discussion titles in patients' online community related to antidepressants and anxiolytics. To examine the content of these titles automatically, we used text mining methods, such as word frequency in a document-term matrix and co-occurrence of words using a network analysis. It was thus possible to identify topics discussed on the forum. The forum included 2415 discussions on antidepressants and anxiolytics over a period of 3 years. After a preprocessing step, the text mining algorithm identified the 99 most frequently occurring words in titles, among which were escitalopram, withdrawal, antidepressant, venlafaxine, paroxetine, and effect. Patients' concerns were related to antidepressant withdrawal, the need to share experience about symptoms, effects, and questions on weight gain with some drugs. Patients' expression on the Internet is a potential additional resource in addressing patients' concerns about treatment. Patient profiles are close to that of patients treated in psychiatry. ©Adeline Abbe, Bruno Falissard. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.10.2017.

  1. [Adherence to patients antidepressant treatment and the factors associated of non-compiance].

    Science.gov (United States)

    Párraga Martínez, Ignacio; López-Torres Hidalgo, Jesús; del Campo del Campo, José M; Villena Ferrer, Alejandro; Morena Rayo, Susana; Escobar Rabadán, Francisco

    2014-01-01

    To know the adherence to treatment in patients who initiate antidepressant drugs and to analyze the determinant factors of non-compliance, so much clinical as sociodemographic. Prospective longitudinal observational study. Primary Health Care and Mental Health Surgeries of three Castilla-La Mancha Areas. 185 adults patients who were started in antidepressant treatment were evaluated. Treatment adherence (test Haynes-Sackett, test Morisky-Green, count of tablets and MEMS), adverse effects, intensity of depressive symptoms, sociodemographic characteristics and other characteristics related to antidepressants or participants. After 6months of beginning antidepressing treatment, 46.9% (95%IC: 36.5-57.3) showed an inadequate fulfilment by pill count method and 28.6% (95%IC: 19.1-38.0) with Morisky-Green's questionnaire. To 15 days the lack of adherence was 48.5% (95%IC: 40.6-56.4) and of 33.5% (95%IC: 26.1-41.0). The 38.4% (95%IC: 31.1-45.7) demonstrated some side effect during the follow-up. Using proportional risk model of Cox the variables related to compliance were: younger age, level of instruction lower than secondary studies, free medicines for pensioner, no psychotherapeutic treatment, consume a fewer antidepressants drugs and a frequency ≤ 3 visits to the family doctor 3 months previous to the study. The non-compliance of antidepressant treatment in primary care is high from the first weeks after initiating it. The conditioning factors are related to sociodemographic characteristics and other patient characteristics as type of financing of pharmaceutical benefit and frequentness at primary care. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  2. Evaluation of antidepressant activity of vanillin in mice.

    Science.gov (United States)

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

    2013-01-01

    The main objective of this study was to evaluate antidepressant activity of vanillin in mice models of depression. Animals were divided into five groups, consisting six mice in each group. Out of these, three groups served as control (distilled water, imipramine,and fluoxetine) and the remaining two groups received test drug in two different doses (10 mg/kg and 100 mg/kg). All the drugs were administered orally one hour before the test procedure for acute study and daily for ten days for chronic study. Mice were subjected to forced swim (FST) and tail suspension tests (TST). Both the doses of vanillin reduced the immobility duration in TST as well as in FST. In TST, there was a statistically significant decrease in the immobility in all the groups when compared to the control (distilled water) group. But the reduction of immobility in FST did not show statistically significant reduction in immobility in the groups treated with vanillin when compared with control. In the chronic study group that received vanillin at a dose of 100 mg/kg, the immobility reduction was significantly lower when compared to the group receiving fluoxetine. Vanillin at the dosage of 100 mg/kg has demonstrated antidepressant activity in mice, which is comparable with fluoxetine.

  3. Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons

    Directory of Open Access Journals (Sweden)

    Nadine eBeckmann

    2014-09-01

    Full Text Available Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer’s disease and major depression, as well as viral (e.g. measles virus and bacterial (e.g. Staphylococcus aureus, Pseudomonas aeruginosa infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug.

  4. Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease

    Science.gov (United States)

    Cannas, Giovanna; Poutrel, Solène; Thomas, Xavier

    2017-01-01

    While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome. PMID:28293403

  5. HYDROXYCARBAMINE: FROM AN OLD DRUG USED IN MALIGNANT HEMOPATHIES TO A CURRENT STANDARD IN SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Giovanna Cannas

    2017-02-01

    Full Text Available While hydroxycarbamine (hydroxyurea, HU has less and less indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support of safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. HU has become the standard-of-care for sickle cell anemia, but remains underused. Barriers to its use should be identified and overcome.

  6. Are older people prescribed antidepressants on the basis of fewer symptoms of depression, and for longer periods of time? A survey of 1825 New Zealanders.

    Science.gov (United States)

    Read, John; Gibson, Kerry L; Cartwright, Claire

    2016-09-01

    To determine whether older people are prescribed antidepressants at lower levels of depression and with fewer symptoms, and whether they are more likely to engage in chronic usage than younger adults. An online survey about experiences with, and opinions about, depression and antidepressants was completed by 1825 New Zealand adults who had been prescribed antidepressants in the preceding five years. Participants over 55 were prescribed antidepressants with significantly fewer symptoms and were significantly less likely to meet DSM criteria for depression. They were also significantly more likely to have used the drugs for three years and still be using them. Prescribing physicians and their older patients might benefit from discussing the pros and cons of antidepressants (including the additional risk factors with this age group) and the alternatives. If prescription does occur, careful monitoring to avoid unnecessary, potentially damaging, long-term use is recommended. © 2016 AJA Inc.

  7. Antidepressant-induced lipidosis with special reference to tricyclic compounds.

    Science.gov (United States)

    Xia, Z; Ying, G; Hansson, A L; Karlsson, H; Xie, Y; Bergstrand, A; DePierre, J W; Nässberger, L

    2000-04-01

    Cationic amphiphilic drugs, in general, induce phospholipid disturbances. Tricyclic, as well as other antidepressants belong to this group. In experimental animals, antidepressants induce lipid storage disorders in cells of most organs, a so-called generalized phospholipidosis. This disorder is conveniently detected by electron microscopic examination revealing myelin figures. Myelin figures or myeloid bodies are subcellular organelles containing unicentric lamellar layers. The lipidotic induction potency during in vivo is related to the apolarity of the compound. Metabolism of phospholipids takes place within the cell continuously. Several underlying mechanisms may be responsible for the induction of the phospholipid disturbance. For instance, it has been suggested that the compounds bind to phospholipids and such binding may alter the phospholipid's suitability as a substrate for phospholipases. Free TCA or metabolites thereof may also inhibit phospholipases directly, as has been demonstrated for sphingomyelinase in glioma and neuroblastoma cells. Both these mechanisms might result in phospholipidosis. Interaction between drug and phospholipid bilayer has been investigated by nuclear magnetic resonance technique. There seems to be large differences in the sensitivities amongst different organs. Steroid-producing cells of the adrenal cortex, testis and ovaries are in particular susceptible to drug-induced lipidosis. The so-called foam cells are lung macrophages located in the interstitium which become densely packed with myelin figures during TCA exposure. It requires about 3-6 weeks of treatment to develop this converted cell. In cell cultures however, phospholipidosis is demonstrated already after 24 h only. It appears that the cells that undergo TCA-induced lipidosis may recover after withdrawal of the drug. The time required to achieve complete recovery ranges from 3-4 weeks to several months, depending on the organ affected. Little is known about the

  8. Predicting a single HIV drug resistance measure from three international interpretation gold standards.

    Science.gov (United States)

    Yashik, Singh; Maurice, Mars

    2012-07-01

    To investigate the possibility of combining the interpretation of three gold standard interpretation algorithms using weighted heuristics in order to produce a single resistance measure. The outputs of HIVdb, Rega, ANRS were combined to obtain a single resistance profile using the equally weighted voting algorithm, accuracy based weighing voting algorithm and the Bayesian based weighted voting algorithm techniques. The Bayesian based voting combination increased the accuracy of the resistance profile prediction compared to phenotype, from 58% to 69%. The equal weighted voting algorithm and the accuracy based algorithm both increased the prediction accuracy to 60%. From the result obtained it is evident that combining the gold standard interpretation algorithms may increase the predictive ability of the individual interpretation algorithms. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  9. Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin

    Directory of Open Access Journals (Sweden)

    Franco Cavaleri

    2018-01-01

    Full Text Available Various parts of the turmeric plant have been used as medicinal treatment for various conditions from ulcers and arthritis to cardiovascular disease and neuroinflammation. The rhizome’s curcumin extract is the most studied active constituent, which exhibits an expansive polypharmacology with influence on many key inflammatory markers. Despite the expansive reports of curcucmin’s therapeutic value, clinical reliability and research repeatability with curcumin treatment are still poor. The pharmacology must be better understood and reliably mapped if curcumin is to be accepted and used in modern medical applications. Although the polypharmacology of this extract has been considered, in mainstream medicine, to be a drawback, a perspective change reveals a comprehensive and even synergistic shaping of the NF-kB pathway, including transactivation. Much of the inconsistent research data and unreliable clinical outcomes may be due to a lack of standardization which also pervades research standard samples. The possibility of other well-known curcumin by-products contributing in the polypharmacology is also discussed. A new flowchart of crosstalk in transduction pathways that lead to shaping of nuclear NF-kB transactivation is generated and a new calibration or standardization protocol for the extract is proposed which could lead to more consistent data extraction and improved reliability in therapy.

  10. Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin.

    Science.gov (United States)

    Cavaleri, Franco

    2018-01-01

    Various parts of the turmeric plant have been used as medicinal treatment for various conditions from ulcers and arthritis to cardiovascular disease and neuroinflammation. The rhizome's curcumin extract is the most studied active constituent, which exhibits an expansive polypharmacology with influence on many key inflammatory markers. Despite the expansive reports of curcucmin's therapeutic value, clinical reliability and research repeatability with curcumin treatment are still poor. The pharmacology must be better understood and reliably mapped if curcumin is to be accepted and used in modern medical applications. Although the polypharmacology of this extract has been considered, in mainstream medicine, to be a drawback, a perspective change reveals a comprehensive and even synergistic shaping of the NF-kB pathway, including transactivation. Much of the inconsistent research data and unreliable clinical outcomes may be due to a lack of standardization which also pervades research standard samples. The possibility of other well-known curcumin by-products contributing in the polypharmacology is also discussed. A new flowchart of crosstalk in transduction pathways that lead to shaping of nuclear NF-kB transactivation is generated and a new calibration or standardization protocol for the extract is proposed which could lead to more consistent data extraction and improved reliability in therapy.

  11. Antidepressant and Anxiolytic Potentials of Dichloromethane ...

    African Journals Online (AJOL)

    Furthermore, a diminution in the anxiety response was also observed against elevated plus maze and light dark tests, which signify its anti-anxiety activity when compared with standard anxiolytic drug, diazepam. Moreover, DMHBR has no significant effects on both the motor coordination of the mice in the rota rod test and ...

  12. Antidepressant effect of taurine in diabetic rats.

    Science.gov (United States)

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

    2012-10-01

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

  13. Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies.

    Science.gov (United States)

    Perrot, S; Javier, R-M; Marty, M; Le Jeunne, C; Laroche, F

    2008-08-01

    The aim of this study was to review the evidence supporting the use of anti-depressants in painful rheumatological conditions. A systematic review of papers published between 1966 and 2007, in five European languages, on anti-depressants in rheumatological conditions was performed. Papers were scored using Jadad method and analgesic ES was calculated. We selected 78 clinical studies and 12 meta-analyses, from 140 papers. The strongest evidence of an analgesic effect of anti-depressants has been obtained for fibromyalgia. A weak analgesic effect is observed for chronic low back pain, with an efficacy level close to that of analgesics. In RA and AS, there is no analgesic effect of anti-depressants, but these drugs may help to manage fatigue and sleep disorders. There is no clear evidence of an analgesic effect inOA, but studies have poor methodological quality. Analgesic effects of anti-depressants are independent of their anti-depressant effects. Tricyclic anti-depressants (TCAs), even at low doses, have analgesic effects equivalent to those of serotonin and noradrenalin reuptake inhibitors (SNRIs), but are less well tolerated. Selective serotonin reuptake inhibitors (SSRIs) have modest analgesic effects, but higher doses are required to achieve analgesia. Anti-depressant drugs, particularly TCAs and SNRIs, have analgesic effects in chronic rheumatic painful states in which analgesics and NSAIDs are not very efficient, such as fibromyalgia and chronic low back pain. In inflammatory rheumatic diseases, anti-depressants may be useful for managing fatigue and sleep disorders. Further studies are required to compare anti-depressants with other analgesics in the management of chronic painful rheumatological conditions.

  14. Antidepressant use and risk for preeclampsia.

    Science.gov (United States)

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

    2013-09-01

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

  15. HPLC Fingerprinting of Sennosides in Laxative Drugs with Isolation of Standard Substances from Some Senna Leaves

    Directory of Open Access Journals (Sweden)

    L. Omur Demirezer

    2011-01-01

    Full Text Available Senna leaves are one of the oldest medicinal herbs and they are used as laxative. Herbal teas which contain senna leaves are most commonly used to promote weight loss. The quality control of slimming teas which contain Senna leaves and also pharmaceutical preparations including Senna extract enriched by sennoside B was achieved by HPLC fingerprinting method. While the presence of sennoside A and B in laxative drugs was proved, it was seen to be devoid of sennosides in slimming teas. Kaempferol 3-O-β-D-gentiobioside (1, aloe-emodine 8-O-β-D-glucopyranoside (2, rhein 8-O-β-D-glucopyranoside (3, torachrysone 8-O-β-D-glucopyranoside (4, isorhamnetine 3-O-β-D-gentiobioside (5 were also isolated from Senna leaves.

  16. Industry Perspective on Standardizing Food-Effect Studies for New Drug Development.

    Science.gov (United States)

    Marroum, Patrick J; Nuthalapati, Silpa; Parikh, Apurvasena; Shebley, Mohamad; Hoffman, David; Zha, Jiuhong; Khatri, Amit; Awni, Walid M

    2018-02-19

    Investigating the effect of food on bioavailability during the development of an oral drug product is of prime importance because it has major implications on the study design of the clinical trials and dosing and administration recommendations. For modified-release formulations that exhibit dose dumping when administered with food, this may result in clinical concerns around safety and efficacy. In this article, we provide an overview of the various considerations in our opinion that impact the design and conduct of food-effect studies. We summarize the various recommendations from the different regulatory agencies and provide specific suggestions on study conduct in terms of statistical design, timing of studies, subject selection, and type and caloric content of the meal. We also discuss the role of modeling and simulation. Finally, we present an interpretation of the results of food-effect studies in addition to dosing and labeling recommendations in relation to regulatory guidance documents.

  17. Automated identification of drug and food allergies entered using non-standard terminology.

    Science.gov (United States)

    Epstein, Richard H; St Jacques, Paul; Stockin, Michael; Rothman, Brian; Ehrenfeld, Jesse M; Denny, Joshua C

    2013-01-01

    An accurate computable representation of food and drug allergy is essential for safe healthcare. Our goal was to develop a high-performance, easily maintained algorithm to identify medication and food allergies and sensitivities from unstructured allergy entries in electronic health record (EHR) systems. An algorithm was developed in Transact-SQL to identify ingredients to which patients had allergies in a perioperative information management system. The algorithm used RxNorm and natural language processing techniques developed on a training set of 24 599 entries from 9445 records. Accuracy, specificity, precision, recall, and F-measure were determined for the training dataset and repeated for the testing dataset (24 857 entries from 9430 records). Accuracy, precision, recall, and F-measure for medication allergy matches were all above 98% in the training dataset and above 97% in the testing dataset for all allergy entries. Corresponding values for food allergy matches were above 97% and above 93%, respectively. Specificities of the algorithm were 90.3% and 85.0% for drug matches and 100% and 88.9% for food matches in the training and testing datasets, respectively. The algorithm had high performance for identification of medication and food allergies. Maintenance is practical, as updates are managed through upload of new RxNorm versions and additions to companion database tables. However, direct entry of codified allergy information by providers (through autocompleters or drop lists) is still preferred to post-hoc encoding of the data. Data tables used in the algorithm are available for download. A high performing, easily maintained algorithm can successfully identify medication and food allergies from free text entries in EHR systems.

  18. Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Carina Riediger

    2017-07-01

    tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.

  19. Antidepressants share the ability to increase catecholamine output in the bed nucleus of stria terminalis: a possible role in antidepressant therapy?

    Science.gov (United States)

    Cadeddu, Roberto; Ibba, Marcello; Sadile, Adolfo; Carboni, Ezio

    2014-05-01

    Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria teminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. The aim of this study, carried out by means of in vivo microdialysis, was to ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST. We observed that all the antidepressants tested (5-20 mg/kg i.p.) increased the output of catecholamines, dose dependently. In particular, the maximum increases (as a percent of basal) for norepinephrine and dopamine respectively, were as follows: desipramine, 239 and 137; reboxetine, 185 and 128; imipramine, 512 and 359; citalopram, 95 and 122; fluoxetine, 122 and 68; bupropion, 255 and 164. These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders.

  20. Genome-wide pharmacogenetics of antidepressant response in the GENDEP project

    DEFF Research Database (Denmark)

    Uher, Rudolf; Perroud, Nader; Ng, Mandy Y.M.

    2010-01-01

    : High-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project......Objective: The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs. Method...... and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline. Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene...

  1. 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.

  2. Clinically relevant interactions between newer antidepressants and second-generation antipsychotics.

    Science.gov (United States)

    Spina, Edoardo; de Leon, Jose

    2014-05-01

    Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them. This paper comprehensively reviews PD DI and PK DI studies. More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes.

  3. Pain Relief in Depressive Disorders: A Meta-Analysis of the Effects of Antidepressants.

    Science.gov (United States)

    Gebhardt, Stefan; Heinzel-Gutenbrunner, Monika; König, Udo

    2016-12-01

    Pain is a common symptom in patients with depressive disorders, which, if present, worsens the prognosis. However, there is little empirical knowledge of the therapeutic effects of antidepressants on painful physical symptoms of patients with depressive disorders. Furthermore, tricyclic/tetracyclic antidepressants (TCAs) have not yet been included in existing meta-analyses. A broad, systematic search of PubMed literature on antidepressant drug treatment of patients with depressive disorders with comorbid pain symptoms was carried out. A random-effects meta-analysis has been performed among 3 different groups of drugs for the 2 end points: pain and depression. Fourteen placebo-controlled studies with selective serotonin-noradrenaline reuptake inhibitors (SSNRIs) could be included, with 3 of them also investigating selective serotonin reuptake inhibitors (SSRIs). Three further placebo-controlled SSRI studies were identified, but only 2 placebo-controlled TCA studies.Both SSNRIs and SSRIs, but not TCAs, were significantly superior to placebo as regards their analgesic effects. However, all effects were small. For SSNRIs, there was a strong positive correlation between their effectiveness for pain relief and their positive effect on the mood of the patients. The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent. Because of a lack of placebo-controlled TCA studies, the results for TCAs would be comparable only to those of SSRIs and SSNRIs, if non-placebo-controlled TCA studies were included. The positive correlation found indicates a close relationship of pain relief and antidepressant treatment effects. These results refer merely to patients with primary depressive disorders, not to patients with primary pain disorders. Further studies comparing the effects of different types of antidepressant drugs on pain in depressive patients are warranted.

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

    Directory of Open Access Journals (Sweden)

    David Arterburn

    2016-04-01

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

  5. Low dose of caffeine enhances the efficacy of antidepressants in major depressive disorder and the underlying neural substrates.

    Science.gov (United States)

    Liu, Qing-Shan; Deng, Ran; Fan, Yuyan; Li, Keqin; Meng, Fangang; Li, Xueli; Liu, Rui

    2017-08-01

    Caffeine is one of the most frequently used psychoactive substances ingested mainly via beverage or food products. Major depressive disorder is a serious and devastating psychiatric disorder. Emerging evidence indicates that caffeine enhances the antidepressant-like activity of common antidepressant drugs in rodents. However, whether joint administration of low dose of caffeine enhances the antidepressant actions in depressed patients remains unclear. A total of 95 male inpatients were assigned to three groups and were asked to take either caffeine (60, 120 mg) or placebo (soymilk powder) daily for 4 wk on the basis of their current antidepressant medications. Results showed that chronic supplementation with low dose of caffeine (60 mg) produced rapid antidepressant action by reduction of depressive scores. Furthermore, low dose of caffeine improved cognitive performance in depressed patients. However, caffeine did not affect sleep as measured by overnight polysomnography. Moreover, chronic caffeine consumption elicited inhibition of hypothalamic-pituitary-adrenal axis activation by normalization of salivary cortisol induced by Trier social stress test. These findings indicated the potential benefits of further implications of supplementary administration of caffeine to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 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

  7. Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy.

    Science.gov (United States)

    Simó, Marta; Velasco, Roser; Graus, Francesc; Verger, Eugenia; Gil, Miguel; Pineda, Estela; Blasco, Jaume; Bruna, Jordi

    2012-07-01

    Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent limiting-dose effect of temozolomide (TMZ). The aim of the study was to investigate the impact of AEDs on thrombocytopenia in GBM patients treated with radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use, platelet count, and accumulated TMZ dose were analyzed at each cycle. Thrombocytopenia was operationalized as a continuous platelet count and a dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the threshold beyond which TMZ treatment is modified. A linear and a probit pooled cross-sectional regression analysis were used to study the impact of age, gender, AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was also analyzed. Thirty-five patients (35%) presented seizures at onset and 18 (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control. Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p = 0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p = 0.001). Recursive Partitioning Analysis prognostic class was the only variable with significant impact on survival. Valproate and age had an independent negative effect on total platelet count, although neither had an effect on critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of valproate in GBM patients might not be justified. Nevertheless, this negative effect may be taken into account especially in elderly patients.

  8. The Effects of Fall-Risk-Increasing Drugs on Postural Control : A Literature Review

    NARCIS (Netherlands)

    de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.

    2013-01-01

    Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of

  9. Drug and poison information - the Tygerberg experience

    African Journals Online (AJOL)

    100. TABLE VI. Pharmacotherapy consultations. Drug categories. Antimicrobial. Cardiovascular. Anti-epileptic. Neuroleptic and anti-histamine. Antidepressant. Benzodiazepines, barbiturates and other sedative hypnotics. Respiratory. Miscellaneous. Total. 1986 - 1988. 1990 - 1991. No. %. No. %. Average (%). 312. 29,1.

  10. Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: retrospective study (STACCATO).

    Science.gov (United States)

    Panisset, Michel; Chen, Jack J; Rhyee, Sean H; Conner, Jill; Mathena, Julie

    2014-12-01

    The serotonin toxicity syndrome (STS) is a potential risk with concurrent use of the monoamine oxidase type-B inhibitor rasagiline and antidepressants. To assess systematically the occurrence of STS in patients with Parkinson disease (PD) treated with rasagiline plus antidepressants (R+ATD), rasagiline without antidepressants (R), or antidepressants plus anti-PD dopaminergic medications (ATD) other than either rasagiline or selegiline. A phase IV multicenter retrospective cohort study was conducted of patients with PD who began receiving R+ATD, R, or ATD between September 1, 2006, and December 31, 2008. Medical records were reviewed for patient demographics, treatment details, and hospitalizations/emergency department (ED) visits. An adjudication committee independently reviewed records to verify case ascertainment and used the Hunter Serotonin Toxicity Criteria for case definition. Outcome variables were analyzed by descriptive statistics. A total of 1504 patients with PD (471 with R+ATD; 511 with R; and 525 with ATD) were enrolled from 37 sites. In the R+ATD and ATD groups, selective serotonin reuptake inhibitors (SSRIs) were most frequently used (74.5% and 77%, respectively). In the R+ATD and ATD groups, mean duration of antidepressant use (tricyclic, SSRI, and other) were 50.5-53.5 weeks and 51.7-80.9 weeks, respectively. Overall, 195 patients (13%) from all three groups had one or more hospitalization/ED visits. No cases of STS were identified in any group. In this large multicenter retrospective cohort study, concurrent administration of R+ATD was not associated with STS. The findings of this phase IV study expand the drug interaction and pharmacovigilance safety awareness for the use of antidepressants in patients with PD. © 2014 Pharmacotherapy Publications, Inc.

  11. Antidepressant-Like Actions of Inhibitors of Poly(ADP-Ribose) Polymerase in Rodent Models.

    Science.gov (United States)

    Ordway, Gregory A; Szebeni, Attila; Hernandez, Liza J; Crawford, Jessica D; Szebeni, Katalin; Chandley, Michelle J; Burgess, Katherine C; Miller, Corwin; Bakkalbasi, Erol; Brown, Russell W

    2017-12-01

    Many patients suffering from depressive disorders are refractory to treatment with currently available antidepressant medications, while many more exhibit only a partial response. These factors drive research to discover new pharmacological approaches to treat depression. Numerous studies demonstrate evidence of inflammation and elevated oxidative stress in major depression. Recently, major depression has been shown to be associated with elevated levels of DNA oxidation in brain cells, accompanied by increased gene expression of the nuclear base excision repair enzyme, poly(ADP-ribose) polymerase-1. Given these findings and evidence that drugs that inhibit poly(ADP-ribose) polymerase-1 activity have antiinflammatory and neuroprotective properties, the present study was undertaken to examine the potential antidepressant properties of poly(ADP-ribose) polymerase inhibitors. Two rodent models, the Porsolt swim test and repeated exposure to psychological stressors, were used to test the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, for potential antidepressant activity. Another poly(ADP-ribose) polymerase inhibitor, 5-aminoisoquinolinone, was also tested. Poly(ADP-ribose) polymerase inhibitors produced antidepressant-like effects in the Porsolt swim test, decreasing immobility time, and increasing latency to immobility, similar to the effects of fluoxetine. In addition, 3-aminobenzamide treatment increased sucrose preference and social interaction times relative to vehicle-treated control rats following repeated exposure to combined social defeat and unpredictable stress, mediating effects similar to fluoxetine treatment. The poly(ADP-ribose) polymerase inhibitors 3-aminobenzamide and 5-aminoisoquinolinone exhibit antidepressant-like activity in 2 rodent stress models and uncover poly(ADP-ribose) polymerase as a unique molecular target for the potential development of a novel class of antidepressants.

  12. [Modification of sexual functions by antidepressants].

    Science.gov (United States)

    Baier, D; Philipp, M

    1994-01-01

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

  13. Dealing With Depression: Antidepressant Skills for Teens

    OpenAIRE

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

    2005-01-01

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

  14. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

  15. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study.

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients' engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants ( n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed.

  16. Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

    Directory of Open Access Journals (Sweden)

    Mario Degli Stefani

    2016-10-01

    Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

  17. Association between depressive symptoms and metabolic syndrome is not explained by antidepressant medication: results from the PPP-Botnia Study.

    Science.gov (United States)

    Pyykkönen, Antti-Jussi; Räikkönen, Katri; Tuomi, Tiinamaija; Eriksson, Johan G; Groop, Leif; Isomaa, Bo

    2012-05-01

    To study whether the frequently reported association between depressive symptoms and the metabolic syndrome (MetS) and its individual components are secondary to the use of antidepressant medication and to established diabetes or cardiovascular diseases (CVD). A population-based, random sample of 4,967 women and men aged 18-75 years. MetS was defined according to the new, harmonized criteria. Glucose tolerance was assessed by oral glucose tolerance test (OGTT). CVD, depressive symptoms, and use of antidepressant medication were self-reported. The odds for having the MetS increased over 10%for each standard deviation increase in depressive symptoms. Users of antidepressant medication had more than 50% increased odds for having the MetS. Depressive symptoms were also associated with higher glucose response during the OGTT, higher serum triglyceride and lower HDL-cholesterol concentrations, and higher waist circumference, while use of antidepressant medication was associated with higher triglycerides, waist circumference, and systolic blood pressure. The associations of depressive symptoms were not secondary to use of antidepressant medication and were not explained by established diabetes or CVD. Depressive symptoms, the MetS, and the individual components of MetS are related. These associations are not driven by use of antidepressant medication, established diabetes, or CVD.

  18. 'Doing the right thing': factors influencing GP prescribing of antidepressants and prescribed doses.

    Science.gov (United States)

    Johnson, Chris F; Williams, Brian; MacGillivray, Stephen A; Dougall, Nadine J; Maxwell, Margaret

    2017-06-17

    prescribing (e.g. fear of depression recurrence), few perceived continuation problems (e.g. lack of safety concerns) and lack of proactive medication review (e.g. patients only present in crisis), all combine to further drive antidepressant prescribing growth over time. GPs strive to 'do the right thing' to help people. Antidepressants are only a single facet of depression treatment. However, increased awareness of drug limitations and regular proactive reviews may help optimise care.

  19. Antidepressant-like effects of aniracetam in aged rats and its mode of action.

    Science.gov (United States)

    Nakamura, K; Tanaka, Y

    2001-11-01

    Aniracetam has been reported to be efficacious for treating poststroke depression, but no studies that basically examined the antidepressive effects have been made. We aimed to test the antidepressant-like property of aniracetam in rats and to clarify the mechanisms of action through the interaction studies with some receptor antagonists. Antidepressant-like effects of aniracetam and various classes of compounds including different antidepressants were examined in a forced swim test with young (9 weeks old) and aged (25-30 months old) rats. Rats were exposed to a 5-min swim in a test session on day 2 following a 15-min swim in a training session on day 1, and immobility time during the period on day 2 was measured. The test compounds were administered subacutely (three doses over 2 days) or acutely (0.5 h before the testing). Standard antidepressants except for tandospirone significantly reduced immobility time in both young and aged rats. Aniracetam (10-100 mg/kg PO) failed to decrease immobility time in young rats, but it (100 mg/kg PO) significantly shortened immobility in aged rats, the effects of which were mainly mimicked by combined treatment of the metabolites, 2-pyrrolidinone and N-anisoyl-GABA. The effects of aniracetam was reversed completely by mecamylamine (10 mg/kg IP) or haloperidol (0.1 mg/kg IP) and slightly by ketanserin (1 m/kg IP) but was potentiated by scopolamine (0.03 mg/kg IP). These results indicate that aniracetam acts more effective when the forced swim stress-induced immobility is accompanied with brain dysfunction that occurs with aging. The antidepressant-like activity of aniracetam, which is probably due to the combined effects of 2-pyrrolidinone and N-anisoyl-GABA, may be mediated by mainly facilitating dopaminergic transmission (dopamine release and dopamine D2 receptor activation) through nicotinic acetylcholine receptor stimulation.

  20. Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine.

    Science.gov (United States)

    Gürbüz Özgür, Börte; Aksu, Hatice; Birincioğlu, Mustafa; Dost, Turhan

    2015-11-01

    Allopurinol is a xanthine oxidase enzyme inhibitor that is widely used for the treatment of hyperuricemia and gout. The activity of tryptophan 2,3-dioxygenase, which metabolizes tryptophan (TRP), is decreased by xanthine oxidase inhibitors, causing TRP levels in the body to be increased. Increases in TRP levels in the brain might have antidepressant effects. The purpose of this study is to evaluate the antidepressant effects of allopurinol compared to those of fluoxetine, which is a proven antidepressant. Thirty-two Wistar albino male rats were divided into four groups (control, 10mg/kg fluoxetine, 50mg/kg allopurinol, 50mg/kg allopurinol+10 mg/kg fluoxetine; n=8 per group), and forced swimming tests were performed before and after 14days of drug administration. Serotonin, 5-hydroxyindolacetic acid and uric acid levels were measured in blood samples after the final treatment. When allopurinol and fluoxetine were administered separately, a decrease in the duration of immobility and an increased duration of swimming were observed in the forced swimming test. The results showed similar antidepressant efficacies between allopurinol and fluoxetine. However, we found no statistically significant difference in the antidepressant effect of the combined therapy versus single drug therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    Directory of Open Access Journals (Sweden)

    Go Taniguchi

    2015-01-01

    All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each, impaired consciousness appeared. Electroencephalography (EEG showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

  2. Neurogenomic evidence for a shared mechanism of the antidepressant effects of exercise and chronic fluoxetine in mice.

    Directory of Open Access Journals (Sweden)

    Guo-Jen Huang

    Full Text Available Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug--fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy.

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

    DEFF Research Database (Denmark)

    Bech, P

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

    Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (-40 to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and β-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Aboukhatwa Marwa A

    2010-01-01

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

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

    African Journals Online (AJOL)

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

  7. 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…

  8. Tricyclic antidepressant overdose necessitating ICU admission ...

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  10. Antidepressant screening and flavonoids isolation from ...

    African Journals Online (AJOL)

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

  11. 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...

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

    African Journals Online (AJOL)

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

  13. Tritiation of unsaturated tricyclic antidepressants for radioimmunoassay

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    African Journals Online (AJOL)

    Adele

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

  15. Response to tricyclic antidepressants: independent of gender?

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    African Journals Online (AJOL)

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

  17. Moderation of antidepressant response by the serotonin transporter gene

    DEFF Research Database (Denmark)

    Huezo-Diaz, Patricia; Uher, Rudolf; Smith, Rebecca

    2009-01-01

    Background: There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR...... is modulated by gender, age and other variants in the serotonin transporter gene. Aims: To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). Method: The 5-HTTLPR and 13 additional markers across...... the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Results: The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more...

  18. Adult hippocampal neurogenesis: Is it the alpha and omega of antidepressant action?

    Science.gov (United States)

    Eliwa, Hoda; Belzung, Catherine; Surget, Alexandre

    2017-10-01

    It is now well established that all clinically available antidepressants share a common aptitude: they increase the production of adult-generated neurons in the dentate gyrus of the hippocampus. This was first observed in animal models and subsequently in human populations, highlighting the clinical relevance of this finding. Later, it was suggested that hippocampal neurogenesis was not an epiphenomenal correlate of antidepressant action but was causally involved. Indeed, when neurogenesis is suppressed, antidepressant compounds can no longer achieve remission. This action of adult-born neurons seems necessary to achieve remission, but less evidence exists to show that it is sufficient alone. In the following decades, a new generation of putative antidepressants that act through different non-monoaminergic mechanisms were proposed in preclinical research as potential therapies. Interestingly, these treatments all increased neurogenesis in animal models of pathological states: this was observed with drugs acting through peptidergic or glutamatergic mechanisms and with neurostimulation strategies not targeting the hippocampus. However, the involvement of neurogenesis was not always causal. To advance further in this field, an understanding of how adult-generated neurons induce therapeutic effects and how this is related to the pathophysiology of depression are required. Copyright © 2017. Published by Elsevier Inc.

  19. Interaction between serotonin 5-HT1A receptors and beta-endorphins modulates antidepressant response.

    Science.gov (United States)

    Navinés, Ricard; Martín-Santos, Rocío; Gómez-Gil, Esther; Martínez de Osaba, María J; Gastó, Cristòbal

    2008-12-12

    Interactions between serotonergic and the endogenous opioid systems have been suggested to be involved in the etiopathogenesis of depression and in the mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors has been shown to increase plasma beta-endorphin (beta-END) levels in animal studies and in healthy humans. To assess interaction abnormalities between 5-HT1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram. The beta-END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in 30 patients with major depression and in 30 age- and sex-matched healthy controls before and after an 8-week treatment with citalopram. Pre-treatment score of the Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Deltamax) and the area under the curve (AUC) of beta-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the beta-END response and the antidepressant response. Buspirone plasma levels were not measured. At baseline, beta-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the beta-END response (Deltamax: pmechanism of action and response to antidepressant drugs.

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

    Directory of Open Access Journals (Sweden)

    Howard R Weeks

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

  1. Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure.

    Science.gov (United States)

    Zhou, Xiaoming; Lu, Jordan Y-F; Darling, Ryan D; Simpson, Kimberly L; Zhu, Xiaoqing; Wang, Fang; Yu, Liping; Sun, Xinde; Merzenich, Michael M; Lin, Rick C S

    2015-02-17

    Abnormal cortical circuitry and function as well as distortions in the modulatory neurological processes controlling cortical plasticity have been argued to underlie the origin of autism. Here, we chemically distorted those processes using an antidepressant drug-exposure model to generate developmental neurological distortions like those characteristics expressed in autism, and then intensively trained altered young rodents to evaluate the potential for neuroplasticity-driven renormalization. We found that young rats that were injected s.c. with the antidepressant citalopram from postnatal d 1-10 displayed impaired neuronal repetition-rate following capacity in the primary auditory cortex (A1). With a focus on recovering grossly degraded auditory system processing in this model, we showed that targeted temporal processing deficits induced by early-life antidepressant exposure within the A1 were almost completely reversed through implementation of a simple behavioral training strategy (i.e., a modified go/no-go repetition-rate discrimination task). Degraded parvalbumin inhibitory GABAergic neurons and the fast inhibitory actions that they control were also renormalized by training. Importantly, antidepressant-induced degradation of serotonergic and dopaminergic neuromodulatory systems regulating cortical neuroplasticity was sharply reversed. These findings bear important implications for neuroplasticity-based therapeutics in autistic patients.

  2. Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway.

    Science.gov (United States)

    Guzmán-Gutiérrez, Silvia Laura; Bonilla-Jaime, Herlinda; Gómez-Cansino, Rocío; Reyes-Chilpa, Ricardo

    2015-05-01

    Linalool and β-pinene are two volatile monoterpenes that possess antidepressant-like activity. These are components of many aromatic plants used in folk medicine around the world to relieve anxiety and depression. In this contribution, we focused on examining the mechanism of action of these compounds. We used mice in the forced swimming test (FST) and antagonist drugs (i.p.) to receptors related to the depression process such as 5-HT1A. To assess the possible contribution of the serotoninergic system, animals were pre-treated with WAY 100635 (a 5-HT1A receptor antagonist) and PCPA (a serotonin synthesis inhibitor).To assess the participation of the noradrenergic system, the animals were pre-treated with yohimbine (an α2 receptor antagonist), propranolol (a β receptor antagonist) and neurotoxin DSP-4 (a noradrenergic neurotoxin). In the dopaminergic system, we used SCH23390 (a D1 receptor antagonist). WAY 100635 blocked the antidepressant-like effect of linalool and β-pinene. In contrast, pretreatment of mice with PCPA did not modify reductions in the immobility time elicited by the two monoterpenes. The yohimbine modified the effect of linalool on immobility time. Propranolol and neurotoxin DSP-4 reversed the anti-immobility effect of β-pinene; also, SCH23390 blocked the antidepressant-like effect of β-pinene. Our results indicate that linalool and β-pinene produce an antidepressant-like effect through interaction with the monoaminergic system.

  3. Molecular determinants for selective recognition of antidepressants in the human serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

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

    2011-01-01

    Inhibitors of the serotonin transporter (SERT) and norepinephrine transporter (NET) are widely used in the treatment of major depressive disorder. Although SERT/NET selectivity is a key determinant for the therapeutic properties of these drugs, the molecular determinants defining SERT/NET selecti......, these findings provide important insight into the molecular basis for SERT/NET selectivity of antidepressants, which can be used to guide rational development of unique transporter inhibitors with fine-tuned transporter selectivity....

  4. Antidepressant prescribing in five European countries: Application of common definitions to assess the prevalence, clinical observations, and methodological implications

    NARCIS (Netherlands)

    Abbing-Karahagopian, V.|info:eu-repo/dai/nl/341589861; Huerta, C.; Souverein, P.C.|info:eu-repo/dai/nl/243074948; De Abajo, F.; Leufkens, H.G.M.|info:eu-repo/dai/nl/075255049; Slattery, J.; Alvarez, Y.; Miret, M.; Gil, M.; Oliva, B.; Hesse, U.; Requena, G.; De Vries, F.|info:eu-repo/dai/nl/303546670; Rottenkolber, M.; Schmiedl, S.; Reynolds, R.; Schlienger, R.G.; De Groot, M.C.H.|info:eu-repo/dai/nl/313936455; Klungel, O.H.|info:eu-repo/dai/nl/181447649; Van Staa, T.P.|info:eu-repo/dai/nl/304827762; Van Dijk, L.; Egberts, A.C.G.|info:eu-repo/dai/nl/162850050; Gardarsdottir, H.|info:eu-repo/dai/nl/321858131; De Bruin, M.L.|info:eu-repo/dai/nl/270270906

    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 prevalence,

  5. Self-reported indications for antidepressant use in a population-based cohort of middle-aged and elderly

    NARCIS (Netherlands)

    N. Aarts (Nikkie); R. Noordam; A. Hofman (Albert); H.W. Tiemeier (Henning); B.H.Ch. Stricker (Bruno); L.E. Visser

    2016-01-01

    textabstractBackground Population-based studies investigating indications for antidepressant prescribing mostly rely on diagnoses from general practitioners. However, diagnostic codes might be incomplete and drugs may be prescribed ‘off-label’ for indications not investigated in clinical trials.

  6. Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice

    Directory of Open Access Journals (Sweden)

    Lieh-Ching Hsu

    2012-01-01

    Full Text Available This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (ULEtOH for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of ULEtOH in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin. Lastly, the researchers analyzed the content of RHY in the ULEtOH. The results showed that ULEtOH exhibited antidepressant-like activity in FST and TST in mice. ULEtOH increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of ULEtOH. ULEtOH inhibited the activity of MAO-A. The amount of RHY in ULEtOH was 17.12 mg/g extract. Our findings support the view that ULEtOH exerts antidepressant-like activity. The antidepressant-like mechanism of ULEtOH may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.

  7. Comparison of alterations in c-fos and Egr-1 (zif268) expression throughout the rat brain following acute administration of different classes of antidepressant compounds.

    Science.gov (United States)

    Slattery, David A; Morrow, John A; Hudson, Alan L; Hill, David R; Nutt, David J; Henry, Brian

    2005-07-01

    The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.

  8. Impact of Antidepressants on Cytokine Production of Depressed Patients in Vitro

    Directory of Open Access Journals (Sweden)

    Alexander Munzer

    2013-11-01

    Full Text Available The interplay between immune and nervous systems plays a pivotal role in the pathophysiology of depression. In depressive episodes, patients show increased production of pro-inflammatory cytokines such as interleukin (IL-1β and tumor necrosis factor (TNF-α. There is limited information on the effect of antidepressant drugs on cytokines, most studies report on a limited sample of cytokines and none have reported effects on IL-22. We systematically investigated the effect of three antidepressant drugs, citalopram, escitalopram and mirtazapine, on secretion of cytokines IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in a whole blood assay in vitro, using murine anti-human CD3 monoclonal antibody OKT3, and 5C3 monoclonal antibody against CD40, to stimulate T and B cells respectively. Citalopram increased production of IL-1β, IL-6, TNF-α and IL-22. Mirtazapine increased IL-1β, TNF-α and IL-22. Escitalopram decreased IL-17 levels. The influence of antidepressants on IL-2 and IL-4 levels was not significant for all three drugs. Compared to escitalopram, citalopram led to higher levels of IL-1β, IL-6, IL-17 and IL-22; and mirtazapine to higher levels of IL-1β, IL-17, IL-22 and TNF-α. Mirtazapine and citalopram increased IL-22 production. The differing profile of cytokine production may relate to differences in therapeutic effects, risk of relapse and side effects.

  9. The interpersonal adverse effects reported by 1008 users of antidepressants; and the incremental impact of polypharmacy.

    Science.gov (United States)

    Read, John; Gee, Aimee; Diggle, Jacob; Butler, Helen

    2017-10-01

    Antidepressant drugs are being prescribed at ever increasing rates internationally, despite marginal benefit compared to placebo and a range of adverse effects. Most studies of adverse effects focus on biological phenomena. This article presents the results of an online survey of 1008 self-selected anti-depressant users in Britain, which asked about five adverse effects in the interpersonal domain. The most commonly reported among participants who took only antidepressants were: Sex Life - 43.7%, Work or Study - 27.0% and Social Life - 23.5%. These rates of interpersonal adverse effects were even higher for the 52% of participants who were also taking one or more other psychiatric drugs. Only about a half (48%) felt they had been given enough information about side effects by the prescriber. Those initially prescribed medication by a psychiatrist were more likely to be on several types of drugs and reported more adverse effects than those whose prescriber was a General Practitioner (GP). Researchers and prescribers are encouraged to pay greater attention to interpersonal adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Non-fatal overdose of duloxetine in combination with other antidepressants and benzodiazepines.

    Science.gov (United States)

    Menchetti, Marco; Gozzi, Beatrice Ferrari; Saracino, Maria Addolorata; Mercolini, Laura; Petio, Carmine; Raggi, Maria Augusta

    2009-01-01

    The pharmaco-toxicological profile of duloxetine, a novel SNRI antidepressant, is still not completely known; in particular, intoxication cases have been scarcely studied. Here a duloxetine overdose case, in combination with other antidepressants and benzodiazepines, is reported and the chemical-clinical correlations discussed; this is probably the first detailed report of such a case. The patient referred to have ingested nine tablets of Cymbalta (more than 500 mg of duloxetine) and high amounts of four other drugs (venlafaxine, trazodone, sertraline and clonazepam). The patient was dozy and confused and some electrolyte imbalances were found. After gastrolavage, toxicological analyses revealed high plasma levels of duloxetine (384 ng/ml) and low levels of the other supposedly involved drugs. The overdose resulted to be not fatal and the outcome was relatively benign, also thanks to the fast emergency assistance. This case suggests that clinicians should be alerted to the possibility of toxic effects caused by simultaneous overdoses of duloxetine and other antidepressants and that caution should be used when prescribing more than one of these drugs to patients at risk of suicide.

  11. Evidence based herbal drug standardization approach in coping with challenges of holistic management of diabetes: a dreadful lifestyle disorder of 21st century.

    Science.gov (United States)

    Chawla, Raman; Thakur, Pallavi; Chowdhry, Ayush; Jaiswal, Sarita; Sharma, Anamika; Goel, Rajeev; Sharma, Jyoti; Priyadarshi, Smruti Sagar; Kumar, Vinod; Sharma, Rakesh Kumar; Arora, Rajesh

    2013-07-04

    Plants by virtue of its composition of containing multiple constituents developed during its growth under various environmental stresses providing a plethora of chemical families with medicinal utility. Researchers are exploring this wealth and trying to decode its utility for enhancing health standards of human beings. Diabetes is dreadful lifestyle disorder of 21st century caused due to lack of insulin production or insulin physiological unresponsiveness. The chronic impact of untreated diabetes significantly affects vital organs. The allopathic medicines have five classes of drugs, or otherwise insulin in Type I diabetes, targeting insulin secretion, decreasing effect of glucagon, sensitization of receptors for enhanced glucose uptake etc. In addition, diet management, increased food fiber intake, Resistant Starch intake and routine exercise aid in managing such dangerous metabolic disorder. One of the key factors that limit commercial utility of herbal drugs is standardization. Standardization poses numerous challenges related to marker identification, active principle(s), lack of defined regulations, non-availability of universally acceptable technical standards for testing and implementation of quality control/safety standard (toxicological testing). The present study proposed an integrated herbal drug development & standardization model which is an amalgamation of Classical Approach of Ayurvedic Therapeutics, Reverse Pharmacological Approach based on Observational Therapeutics, Technical Standards for complete product cycle, Chemi-informatics, Herbal Qualitative Structure Activity Relationship and Pharmacophore modeling and, Post-Launch Market Analysis. Further studies are warranted to ensure that an effective herbal drug standardization methodology will be developed, backed by a regulatory standard guide the future research endeavors in more focused manner.

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

    Science.gov (United States)

    Macdonald, Gordon

    2017-07-01

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

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

    Science.gov (United States)

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

    2012-01-06

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

  14. Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders.

    Science.gov (United States)

    Gupta, Saurabh; Gersing, Kenneth Ronald; Erkanli, Alaattin; Burt, Tal

    2016-06-01

    In 2004 the Food and Drug Administration issued a warning on the risk of suicidality in children and adolescents receiving antidepressants. This was followed by reports of changes in antidepressant prescription patterns, suicidality and other aggressive behaviors, but debate is continuing regarding the nature and magnitude of these changes. We examined a large physician database for impact of the warning on antidepressant prescriptions, suicidality and other aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in adult and pediatric patients. We analyzed electronic database covering over 100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning periods. We compared strength of the association between the measures and the time period with two tests. Multivariate logistic regression analyses were performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0 %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant prescription and 16.1 % were pediatric patients. In post-warning period, there was a greater reduction in adult versus pediatric antidepressant prescription rates. Logistic modeling showed greater likelihood of antidepressant prescription in MDD as compared with anxiety disorders in post-warning period. Pediatric patients were more likely than adults to receive fluoxetine during the post-warning period. There was an overall reduction in suicidality and other aggressive behaviors in the post-warning period. Regulatory warnings may have had an impact on antidepressant benefit/risk assessment and consequent utilization, therapeutic effects, and adverse events. Our observations suggest that psychiatrists may heed regulatory warnings, but may also exert professional independence and discrimination in their application.

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

    Science.gov (United States)

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

    2013-01-01

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

  16. Risco de câncer associado ao uso de antidepressivos Risk of cancer associated with the use of antidepressants

    Directory of Open Access Journals (Sweden)

    Camila Silva Bôaventura

    2007-04-01

    Full Text Available INTRODUÇÃO: Alguns estudos sugerem que o uso de antidepressivos poderia aumentar o risco de câncer. Este estudo visa realizar uma revisão sobre o tema. MÉTODO: Foi feita uma busca nas bases de dados MEDLINE e LILACS, utilizando como palavras de busca antidepressant, cancer e nomes das diferentes drogas antidepressivas. RESULTADOS: Onze artigos foram selecionados. Foram encontrados seis artigos sugerindo uma associação positiva fraca entre o uso de antidepressivos e o crescimento tumoral e cinco artigos que não sugeriam a associação. Discussão: Os resultados dos estudos com relação ao risco de câncer associado ao uso de antidepressivos são ainda conflitantes. Na maioria dos estudos, a análise multivariada não mostra associação positiva em uso de antidepressivos e câncer, a não ser em casos específicos, como linfoma de Hodgkin.INTRODUCTION: Some studies suggest that the use of antidepressants could increase the risk of cancer. This study aims at performing a review on this subject. METHOD: A search was performed in the MEDLINE and LILACS databases using the keywords antidepressant, cancer and names of varied antidepressant drugs. RESULTS: Eleven articles were selected. Six articles were found suggesting a positive weak association between use of antidepressants and tumoral growth. In five articles this association was not found. DISCUSSION: The results of studies on increased risk of cancer associated with antidepressants are still conflicting. In most studies the multivariate analysis did not show positive association between use of antidepressants and cancer, unless in specific cases, such as Hodgkin's lymphoma.

  17. BRAF plus MEK-targeted drugs: a new standard of treatment for BRAF-mutant advanced melanoma.

    Science.gov (United States)

    Queirolo, Paola; Spagnolo, Francesco

    2017-03-01

    BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients. Nevertheless, the development of mechanisms of resistance limits the duration of response to such treatment in the majority of cases, with only about 20% of patients treated with the combination being progression-free at 3 years. The aim of this review is to report the efficacy and safety outcomes of the combination of BRAF plus MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as well as to discuss future perspectives to improve outcomes based on current clinical and translational research studies.

  18. The Most Prevalnet Organism in Diabetic Foot Ulcers and Its Drug Sensitivity and Resistance to Different Standard Antibiotics

    International Nuclear Information System (INIS)

    Nageen, A.

    2016-01-01

    Objective: To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics. Study Design: Adescriptive and cross-sectional study. Place and Duration of Study: Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012. Methodology: Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted. Results: Staphylococcus aureus was the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients. Conclusion: Staphylococcus aureus was the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole. (author)

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

    Science.gov (United States)

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

    2015-07-01

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

  20. Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants

    Directory of Open Access Journals (Sweden)

    Barlati Sergio

    2009-05-01

    Full Text Available Abstract Background The neurotrophin BDNF has been implicated in the regulation of neuroplasticity, gene expression, and synaptic function in the adult brain, as well as in the pathophysiology of neuropsychiatric disorders and the mechanism of action of antidepressants. Antidepressant treatments have been shown to increase the expression of BDNF mRNA, although the changes measured were found to be different depending on various factors. A few studies only have measured levels of BDNF protein after antidepressant treatments, and poor correlation was found between mRNA and protein changes. We studied the time course of expression of BDNF mRNA and protein during drug treatments, in order to elucidate the temporal profile of regulation of this effector and whether mRNA and protein levels correlate. Rat groups were treated for 1, 2 or 3 weeks with fluoxetine or reboxetine; in additional groups drug treatment was followed by a washout week (3+1. Total BDNF mRNA was measured by Real Time PCR, pro- and mature BDNF proteins were measured by Western blot. Results We found that mature BDNF protein is induced more rapidly than mRNA, by both drugs in hippocampus (weeks 1–2 and by reboxetine in prefrontal/frontal cortex (week 1. The temporal profile of BDNF protein expression was largely inconsistent with that of mRNA, which followed the protein induction and reached a peak at week 3. Conclusion These results suggest that BDNF protein is rapidly elevated by antidepressant treatments by posttranscriptional mechanisms, and that induction of BDNF mRNA is a slower process.

  1. 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. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2010-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Toru Kobayashi

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

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

    International Nuclear Information System (INIS)

    Ordway, G.A.; Gambarana, C.; Tejani-Butt, S.M.; Areso, P.; Hauptmann, M.; Frazer, A.

    1991-01-01

    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, 125 I-iodopindolol ( 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 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 125 I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of 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 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 125 I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus

  5. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Katherine E Tansey

    Full Text Available It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study. After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8. No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8 were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D, with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the

  6. Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial.

    Science.gov (United States)

    Stingl, Julia Carolin; Kaumanns, Katharina Luise; Claus, Katrin; Lehmann, Marie-Louise; Kastenmüller, Kathrin; Bleckwenn, Markus; Hartmann, Gunther; Steffens, Michael; Wirtz, Dorothee; Leuchs, Ann-Kristin; Benda, Norbert; Meier, Florian; Schöffski, Oliver; Holdenrieder, Stefan; Coch, Christoph; Weckbecker, Klaus

    2016-04-26

    Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of