Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults Prediction of the response to citalopram and reboxetine in post-stroke depressed patients World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision Clinical and Neurobiological Effects of Tianeptine and Paroxetine in Major Depression GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol Notes on the use of fluvoxamine as treatment of depression in HIV-1-infected subjects. Efficacy and Tolerability of Reboxetine Compared with Citalopram: A Double-blind Study in Patients with Major Depressive Disorder Efficacy of venlafaxine in major depression resistant to selective serotonin reuptake inhibitors Cardiac side‐effects of two selective serotonin reuptake inhibitors in middle- aged and elderly depressed patients Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Reboxetine, the first selective noradrenaline reuptake inhibitor antidepressant: Efficacy and tolerability in 2613 patients Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction. Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors. Safety and Tolerability of Dexmecamylamine (TC-5214) Adjunct to Ongoing Antidepressant Therapy in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy: Results of a Long-Term Study The diagnosis and treatment of generalized anxiety disorder. 5-HTTLPR modulates antidepressant efficacy in depressed women Pharmacogenetics of antidepressant medication intolerance. Start of a selective serotonin reuptake inhibitor (SSRI) and increase of antiparkinsonian drug treatment in patients on levodopa. Combination of inositol and serotonin reuptake inhibitors in the treatment of depression Serotonin transporter gene polymorphism and antidepressant response Does comorbid substance use disorder impair recovery from major depression with SSRI treatment? An analysis of the STAR*D level one treatment outcomes.
Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage Background Early rehabilitation after stroke is essential to help reduce disability . Purpose To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke . Data Sources English- language search es of multiple electronic data bases from April 2009 through July 2018 ; targeted search es to December 2018 for studies of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin-norepinephrine reuptake inhibitors . Study Selection 19 systematic review s and 37 r and omized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke . Data Extraction One investigator abstract ed the data , and quality and GRADE assessment were checked by a second investigator . Data Synthesis Most interventions ( for example , SSRIs , mental practice , mirror therapy ) did not improve motor function . High- quality evidence did not support use of fluoxetine to improve motor function . Moderate- quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living ( ADLs ) . Low- quality evidence supported use of robotic arm training to improve ADLs . Low- quality evidence indicated that antidepressants may reduce depression , whereas the frequency and severity of antidepressant-related adverse effects was unclear . Low- quality evidence suggested that cognitive behavioral therapy and exercise , including mind-body exercise , may reduce symptoms of depression and anxiety . Limitation Studies were of poor quality , interventions and comparators were heterogeneous , and evidence on harms was scarce . Conclusion Cardiorespiratory training , repetitive task training , and transcranial direct current stimulation may improve ADLs in adults with stroke .  Cognitive behavioral therapy , exercise , and SSRIs may reduce symptoms of poststroke depression , but use of SSRIs to prevent depression or improve motor function was not supported . Primary Funding Source U.S. Department of Veterans Affairs , Veterans Health Administration OBJECTIVE To compare the emergent sexual effects of moclobemide and selective serotonin reuptake inhibitors ( SSRIs ) during acute and maintenance therapy in routine practice . METHOD 268 patients were evaluated for sexual function  at baseline , 6 weeks , 3 and 6 months of treatment using physician ratings and self-rating question naires . Patients received moclobemide , an reversible monoamine oxidase A inhibitor ( RIMA ) , or a SSRI ( fluoxetine , fluvoxamine , paroxetine , sertraline ) . RESULTS Baseline values were similar in all groups . Incidences of impairments of sexual functioning with treatment , whether clinical ly relevant or not , were 24.3 % with moclobemide and 61.5 % with SSRIs ( physician ratings ) , with no significant tolerance to these effects . There was a suggestion of differences between the SSRIs in their specific dysfunctions they cause . SSRIs ( 21.6 % of patients ) had about ten times the moclobemide rate ( 1.9 % ) of sexual dysfunction reported as adverse events . Antidepressant efficacy was comparable between treatments . CONCLUSION In patients for whom sexual function  is important or sexual dysfunction  is present , moclobemide should be considered a first line antidepressant Rationale and objective Depression is a significant complication of stroke . The effectiveness of antidepressant drugs in the management of post-stroke depression ( PSD ) has been widely investigated . However , the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies . Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor ( SSRI ) , citalopram , and a noradrenaline reuptake inhibitor ( NARI ) , reboxetine , in post-stroke patients affected by anxious depression or retarded depression . Methods This was a r and omized double-blind study . Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table . R and omisation was planned so that 50 % of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50 % were assigned to treatment with reboxetine . The Beck Depression Inventory ( BDI ) , the Hamilton Depression Rating Scale ( HDRS ) and a synoptic table were used to score depressive symptoms . Results Both citalopram and reboxetine showed good safety and tolerability . Citalopram exhibited greater efficacy in anxious depressed patients , while reboxetine was more effective in retarded depressed patients . Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects . In addition , PSD patients should be classified according to their clinical profile ( similarly to patients affected by primary depression ) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines Selective serotonin reuptake inhibitors ( SSRIs ) are widely used as effective pharmacological agents to treat depressive disorders . In contrast to the SSRIs , which block the presynaptic serotonin ( 5-HT ) transporter and by this route increase the concentration of serotonin in the synaptic cleft , the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission . Both SSRIs and tianeptine are clinical ly effective ; however , their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission . To better underst and the differences between these two opposite pharmacological modes of action , we compared the changes induced by tianeptine and paroxetine on psychopathology , the hypothalamic-pituitary-adrenocortical ( HPA ) system , and cognitive functions in a double-blind , r and omized , controlled trial including 44 depressed in patients over a period of 42 days .  Depressive symptomatology significantly improved in all efficacy measures , with no significant differences between tianeptine and paroxetine . There was a trend toward better response to the SSRI among women . Assessment of the HPA system showed marked hyperactivity before the beginning of treatment , which then normalized in most of the patients , without significant differences between the two antidepressants . Cognitive assessment s showed no significant differences between the two drugs investigated . The results of the current study suggest that the initial effect , i.e. , enhancement or decrease of 5-HT release , is only indirectly responsible for antidepressant efficacy , and they support the notion that downstream adaptations within and between nerve cells are crucial . The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin ( Selective Serotonin Reuptake Inhibitors – SSRIs ) and noradrenaline ( Noradrenaline Reuptake Inhibitors – NaRIs ) into the presynaptic terminal . There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action . Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs , there are patients who respond to one class of compounds and not another . This suggests that treatment response could be predicted by genetic and /or clinical characteristics . Firstly , this study aims to investigate the influence of a polymorphism ( SLC6A4 ) in the 5HT transporter in altering response to SSRI medication . Secondly , the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs . Methods / design The GenPod trial is a multi-centre r and omised controlled trial . GPs referred patients aged between 18–74 years presenting with a new episode of depression , who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse . Patients were interviewed to ascertain their suitability for the study . Eligible participants ( with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory ( BDI ) score > 14 ) were r and omised to receive one of two antidepressant treatments , either the SSRI Citalopram or the NaRI Reboxetine , stratified according to severity . The final number r and omised to the trial was 601 . Follow-up assessment s took place at 2 , 6 and 12 weeks following r and omisation . Primary outcome was measured at 6 weeks by the BDI . Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments . Discussion The results of the trial will provide information about targeting antidepressant treatment for individual patients ; in turn this may increase prescribing efficacy , thereby speeding recovery and reducing the cost to the NHS . It will also help to underst and the different roles that noradrenaline and serotonin might play in the biology of depression . The trial is expected to report in the autumn of 2008.Trial Registration IS RCT N Fluvoxamine belongs to the class of selective serotonin reuptake inhibitors ( SSRIs ) which have recently gained large popularity as antidepressant agents essentially because they lack the most troublesome adverse effects of older antidepressants ( i.e. tricyclic antidepressants ) such as anticholinergic effects and cardiotoxicity . Recent studies in the literature suggest that HIV-1 infected subjects are affected by depressive episodes with a relatively high frequency , often requiring an antidepressant treatment . Due to its favorable adverse effects profile , we used fluvoxamine as first line treatment for sixteen depressed HIV-1 infected subjects . They were administered the drug at a daily dosage of 100 mg in the evening . Fluvoxamine provided a good clinical efficacy for six of these patients , whereas the other ten had to discontinue the drug because of the presence of severe adverse effects such as acute total insomnia , gastro-intestinal disturbances together with anorexia , aggressive and impulsive behavior and excessive sedation . The observed fluvoxamine side-effects are not typical or specific for this particular patient group since they are also described in seronegative subjects taking fluvoxamine ; however , our findings seem to indicate that they become more frequent and more severe when the drug is administered to HIV-1 infected patients The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The  dropout number  was 91 in the  reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects .  Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6  Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine  in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD .  Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure " adrenergic " and the other pure " serotonergic . " A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs ) INTRODUCTION Some studies suggest that venlafaxine , due to its pharmacodynamic characteristics , could be an effective drug in depression , resistant to other antidepressive agents . This investigation explores the efficacy and tolerability of venlafaxine in major depression , resistant to a selective serotonin reuptake inhibitor ( SSRI ) . METHODS A multicenter naturalistic study was performed during 6 months and included those patients diagnosed of major depression according to the criteria of DSM-IV who had a minimum score of 18 on the Hamilton Depression Rating Scale ( HAM-D ) and who had not responded to previous treatment with a SSRI at therapeutic doses for a minimum of 4 weeks . The assessment of efficacy was performed with the HAM-D scale , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Rating Scale ( HAM-A ) and the Global Clinical Impression ( GCI ) . Tolerability was evaluated by recording the adverse reactions and with the GCI score on overall drug tolerability . RESULTS A total of 69 patients , of which 59 were evaluable for efficacy ( they had fulfilled at least 4 weeks of treatment ) , were included . About 81 % of all of them obtained a reduction of at least 50 % in the HAM-D , 74 % were considered as " quite improved " or " very improved " in the GCI and 69 % met both criteria . The mean dose of venlafaxine used was 170.4 ( S.D.=43.8 ) mg . Of the 21 patients who did not complete the 6 months of treatment , 3 were due to lack of efficacy , 6 due to adverse effects and 12 for other reasons . About 89.2 % of side effects were considered as mild or moderate . CONCLUSION The results of our study support the efficacy and tolerability of venlafaxine in patients suffering from depression who have not responded to SSRI treatment Selective serotonin reuptake inhibitors ( SSRIs ) are the ‘ new ’ drugs of first choice for the treatment of depression in the older patient . Systematic studies on the effects of SSRIs on cardiac function are scarce , despite the high prevalence of cardiac disorders in the older depressed patient . This is a study which systematic ally assesed cardiac function by echo-cardiography in middle-aged and elderly depressed patients treated with SSRI . In a double-blind r and omized trial , 20 patients were assigned to receive fluvoxamine 20 mg/day or fluoxetine 100mg/day for 6 weeks . Cardiac function was assessed by left ventricle ejection fraction , aortic flow integral and early or passive/late or active mitral inflow , and electrocardiography . Neither SSRI significantly affected cardiac function . Compared with patients without a history of myocardial infa rct ion and /or hypertension , patients with such a history showed a significant improvement in left ventricular ejection fraction . Despite our small study sample , these data indicate that both fluoxetine and fluvoxamine do not affect cardiac function adversely BACKGROUND The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action INTRODUCTION : Reboxetine is the first available selective noradrenaline re-uptake inhibitor ( selective NRI ) . This paper gives an overview of its antidepressant efficacy and tolerability in eight r and omized double-blind , multicentre clinical trials . The clinical profile of reboxetine is also compared with that of the tricyclic antidepressants ( TCAs ) desipramine and imipramine and the selective serotonin re-uptake inhibitor ( SSRI ) fluoxetine . METHODS : Pooled data were analysed from seven short-term ( 4 - 8 weeks ) and one long-term ( up to 1 year ) trials comparing reboxetine with placebo , imipramine , desipramine or fluoxetine . The tolerability of reboxetine was evaluated in 2613 patients with major depression or dysthymia . Data from 1959 patients with major depressive disorder were included to assess drug efficacy . Efficacy was principally assessed using the Hamilton Depression Rating Scale ( HAM-D ) . RESULTS : Reboxetine was more effective than placebo in three of four short-term trials , and it was as effective as fluoxetine , imipramine and desipramine . In long-term treatment , reboxetine was more effective than placebo in preventing relapse ( S 50 % increase in HAM-D ) and recurrence ( HAM-D total score h 10 ) . In a subset of severely depressed patients , reboxetine was as effective as imipramine and significantly more effective than fluoxetine . Reboxetine was as effective as imipramine in the elderly , but better tolerated . The most common adverse events among the 1503 patients ( adults and elderly ) who received reboxetine were dry mouth ( 22 % ) , constipation ( 15 % ) , sweating ( 12 % ) and insomnia ( 11 % ) . Overall , reboxetine was well tolerated , as well as the SSRI fluoxetine and better than the TCAs imipramine and desipramine . CONCLUSIONS : Reboxetine is effective and well tolerated in the short and long-term treatment of depression . It is as well tolerated as fluoxetine and better than imipramine and desipramine . ( Int J Psych Clin Pract 2000 ; 4 : 201 - 208 INTRODUCTION Sexual dysfunction is common with serotonergic antidepressants , including selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) , and does not resolve in most patients . Vortioxetine , an antidepressant with a multimodal mechanism of action , has shown low rates of sexual dysfunction in previous major depressive disorder ( MDD ) trials . AIM This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction ( TESD ) . METHODS Participants treated with , and responding to , citalopram , paroxetine , or sertraline were r and omized to switch to either vortioxetine ( 10/20 mg ; n = 225 ) or escitalopram ( 10/20 mg ; n = 222 ) for 8 weeks . Sexual function was assessed using the Changes in Sexual Functioning Question naire Short Form ( CSFQ-14 ) , and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions ( CGI ) scale , and Profile of Mood States brief form ( POMS-brief ) . Safety and tolerability were also assessed . MAIN OUTCOME MEASURES The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment . The MADRS , CGI , and POMS-brief were used to assess antidepressant efficacy . Safety was assessed via adverse events , vital signs , electrocardiograms , laboratory values , weight , and physical examination findings . RESULTS Vortioxetine showed significantly greater improvements in CSFQ-14 total score ( 8.8 ± 0.64 , mean ± st and ard error ) vs. escitalopram ( 6.6 ± 0.64 ; P = 0.013 ) . Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 ( P < 0.05 ) . Antidepressant efficacy continued in both groups , with similar , but slight , improvements in MADRS and CGI scores . Vortioxetine and escitalopram had similar clinical efficacy profiles in this study , with safety profiles similar to previous trials . Nausea ( n = 9 , 4.0 % ) was the most common treatment-emergent adverse event leading to discontinuation of vortioxetine . CONCLUSION Switching antidepressant therapy to vortioxetine may be beneficial for patients experiencing sexual dysfunction during antidepressant therapy with SSRIs To evaluate the possible influence of buspirone on sexual dysfunction in depressed patients treated with a selective serotonin reuptake inhibitor ( SSRI )  , we analyzed data from a placebo-controlled trial design ed to explore the efficacy of buspirone as add-on treatment for patients not responding to an SSRI alone . At baseline , all patients met the criteria for a major depressive episode according to DSM-IV and had received citalopram or paroxetine during a minimum of 4 weeks without responding to the treatment .  Buspirone ( flexible dosage , 20 - 60 mg/day ) or placebo was added to the SSRI for 4 weeks ; the mean daily dose of buspirone at endpoint was 48.5 mg ( SD = 1.0 ) . Sexual dysfunction was evaluated using a structured interview . Before starting medication with buspirone or placebo , 40 % ( 47 of 117 ) reported at least one kind of sexual dysfunction ( decreased libido , ejaculatory dysfunction , orgasmic dysfunction ) . During the 4 weeks of treatment , approximately 58 % of subjects treated with buspirone reported an improvement with respect to sexual function ; in the placebo group , the response rate was 30 % . The difference between placebo and active drug treatment was more pronounced in women than in men . The response was obvious during the first week , with no further improvement during the course of the study . It is suggested that the effect of buspirone on sexual dysfunction is a result of a reversal of SSRI-induced sexual side effects rather than of an antidepressant effect of the drug Abstract Safety and tolerability are important considerations when selecting patients ’ treatment for major depressive disorder . We report the long-term safety and tolerability of the nicotinic channel modulator dexmecamylamine ( TC-5214 ) , adjunct to selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors ( SNRIs ) in patients with major depressive disorder and who had an inadequate response to antidepressants . This 52-week , double-blind , placebo-controlled study explored the long-term safety and tolerability of dexmecamylamine .  Patients were r and omized 3:1 to receive flexibly dosed dexmecamylamine 1 to 4 mg adjunct to SSRI/SNRI or placebo plus SSRI/SNRI . The patient population comprised inadequate responders from 2 Phase III acute  dexmecamylamine  studies ( NCT01157078 [ study 002 ] , NCT01153347 [ study 004 ] ) and de novo patients who responded inadequately during a 6-week open-label antidepressant treatment period preceding r and omization .  Safety and tolerability were assessed by monitoring adverse events , vital signs , and physical and laboratory parameters . Descriptive statistical analyses were performed on most efficacy-related end points . Sustained efficacy was analyzed using logistic regression . Overall , 813 patients were r and omized ( 610 received dexmecamylamine , 203 received placebo ) . In total , 82.4 % and 84.6 % of patients , respectively , experienced an adverse event . Adverse events occurring more frequently with dexmecamylamine vs placebo were constipation ( 19.6 % vs 6.0 % ) , dizziness ( 12.0 % vs 7.0 % ) , and dry mouth ( 9.7 % vs 5.0 % ) . Back pain ( 2.8 % vs 8.5 % ) , weight increase ( 4.4 % vs 7.0 % ) , and fatigue ( 5.6 % vs 7.5 % ) occurred more frequently in placebo-treated patients . No notable differences were observed between dexmecamylamine and placebo for any secondary end point . In this long-term study , safety and tolerability of dexmecamylamine were consistent with that reported in acute Phase III studies of dexmecamylamine BACKGROUND Generalized anxiety disorder  ( GAD ) is a common and serious disease with a lifetime prevalence of 4.3 % to 5.9 % . It is underdiagnosed in primary care . METHODS Recommendations on the treatment of GAD are given on the basis of all available findings from pertinent r and omized trials , retrieved by a selective search of the literature . RESULTS Among psychotherapeutic techniques , various kinds of cognitive behavioral therapy ( CBT ) have been found useful in controlled trials . The drugs of first choice include selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-norepinephine reuptake inhibitors ( SNRIs ) , and the calcium-channel modulator pregabalin . Tricyclic antidepressants are also effective but have more adverse effects than SSRIs . Although benzodiazepines are effective anxiolytic agents for short-term use , they should not be given over the long term because of the danger of addiction . Buspirone , an azapirone , was found to be effective in a small number of trials , but the findings across trials are inconsistent . The response rate of GAD to CBT in published studies lies between 47 % and 75 % , while its response rate to drug treatment lies between 44 % and 81 % . CONCLUSION The treatment of GAD with CBT and drugs is evidence -based and has a good chance of improving the manifestations of the disorder Background As compared with the long variant ( L ) , the short variant ( S ) of the functional polymorphic region of the serotonin transporter gene ( 5-HTTLPR ) has been associated with a lower antidepressant efficacy in major depression , but some replication studies have evidence d contradictory results . Sex differences may explain these contradictory results . Methods One hundred and three in patients ( 74 women and 29 men ) with a major depressive episode were assessed prospect ively for antidepressant efficacy after 4 weeks of treatment with selective serotonin reuptake inhibitors ( SSRI ) and non-SSRI drugs . Results As compared with LL/LS , the SS genotype of the 5-HTTLPR was associated with a lower antidepressant efficacy in depressed women ( 79 vs. 50 % responders , P = 0.035 ) . This result was shown with both SSRI and non-SSRI antidepressants . The logistic regression performed in women showed that response to treatment was related to genotype ( odds ratio=0.15 ; 95 % confidence interval=0.03–0.85 ; P = 0.03 ) and not to other variables . No effect of 5-HTTLPR was found in depressed men . Conclusion Despite a low power , this study suggests a significant effect of 5-HTTLPR genotype on antidepressant efficacy in depressed women but not in men , with both SSRI and non-SSRI drugs . Further research is needed to confirm this result and investigate its underlying mechanisms OBJECTIVE The authors sought to identify genetic markers for antidepressant medication intolerance . Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 ( CYP2D6 ) has been postulated to underlie antidepressant intolerance ( pharmacokinetic effect ) . However , variation in genes encoding serotonin receptors could also explain antidepressant side effects ( pharmacodynamic effect ) . METHOD An 8-week , double-blind , r and omized pharmacogenetic study compared the widely prescribed antidepressants paroxetine ( a selective serotonin reuptake inhibitor [ SSRI ] ) and mirtazapine ( not an SSRI ) in 246 elderly patients with major depression . Genotypes were determined for the 102 T/C single nucleotide polymorphism ( SNP ) in the serotonin 2A ( 5-HT(2A ) ) locus ( HTR2A ) , previously associated with psychotropic medication treatment outcome . Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene . Clinical outcomes included treatment discontinuations , adverse events , medication compliance , and change in mood . RESULTS Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype . There was a significant linear relationship between the number of C alleles and the probability of discontinuation . Side effect severity in paroxetine-treated patients with the C/C genotype was also greater . In contrast , HTR2A 102 T/C genotype had no effect on mirtazapine side effects . CYP2D6 genotype did not predict treatment outcome for either medication . CONCLUSIONS Pharmacodynamic differences among patients due to variant 5-HT(2A ) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance . Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome AIMS We determined whether the start of selective serotonin reuptake inhibitors ( SSRI ) in levodopa users was followed by a faster increase of antiparkinsonian drug treatment . METHODS Selected were all levodopa users of 55 years and older from the PHARMO prescription data base . The rate of increase of  antiparkinsonian drug treatment  was compared using Cox 's proportional hazard model for starters of SSRI ( n = 15 ) with starters of tricyclic antidepressants ( TCA ) ( n = 31 ) and with patients not using antidepressants ( n = 304 ) , and was adjusted for age , gender , and duration of levodopa use . RESULTS The hazard ratio for the SSRI group compared with the TCA group was 4.2 ( 95 % confidence interval 1.4 , 12.6 ) and compared with the second control group was 2.7 ( 1.2 , 5.2 ) . CONCLUSIONS The start of SSRI therapy in levodopa users is followed by a faster increase of antiparkinsonian drug treatment BACKGROUND Inositol has been reported to be an effective treatment in depression , and we hypothesized that inositol addition might enhance or speed up response to  serotonin selective reuptake inhibitors ( SSRI ) . METHODS Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol .  Hamilton Depression Rating Scale was used as an assessment tool at baseline , and 1 , 2 , 3 , and 4 weeks . RESULTS No significant difference was found between the two treatment groups . CONCLUSIONS Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [ e.g. , monoamine oxidase inhibitors ( MAOI ) plus tricyclic antidepressants ( TCA ) , TCA plus lithium ] . By contrast , augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol We examined allelic polymorphisms of the serotonin transporter ( 5-HTT ) gene and antidepressant response to 6 weeks ' treatment with the selective serotonin reuptake inhibitor ( SSRI ) drugs fluoxetine or paroxetine . We genotyped 120 patients and 252 normal controls , using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene . Diagnosis of depression was not associated with 5-HTT polymorphisms . Patients homozygous I/I in intron2 or homozygous s/s in the promoter region showed better responses than all others ( p < 0.0001 , p = 0.0074 , respectively ) . Lack of the I/I allele form in intron 2 most powerfully predicted non-response ( 83.3 % ) . Response to SSRI drugs  is related to allelic variation in the 5-HTT gene in depressed Korean patients Many patients with major depressive disorder ( MDD ) present with concurrent substance use disorders ( SUDs ) , which has been thought to impair their response to antidepressants . Clinicians often delay antidepressant treatment until sustained sobriety has been established . Unfortunately , these comorbid subjects are typically excluded from depression treatment trials , leaving a gap in underst and ing the treatment outcomes . In the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) study , 2876 adult out patients diagnosed with nonpsychotic MDD were prospect ively treated with the selective serotonin-reuptake inhibitor ( SSRI ) , citalopram , and returned for at least one post-baseline visit .  Participants with SUD ( 29 % ) and without SUD ( 71 % ) were compared in regard to baseline clinical and sociodemographic features and treatment response . The group with MDD and SUD was further subdivided into those with alcohol only , drug only , and both alcohol and drug use . Despite clear sociodemographic and clinical differences , there were no significant differences between groups in the time to achieve response or rates of response to citalopram ;  however , those who endorsed both alcohol and drug use had significantly reduced rates of remission and significantly increased times to reach remission compared to the MDD group without SUD . In addition , subjects with MDD and SUD had higher risk of psychiatric serious adverse events ( 3.3 % vs. 1.5 % ) and hospitalization ( 2.8 % vs. 1.2 % ) . The results indicate that first-line treatment with citalopram in depressed patients with alcohol or drug use respond as well as those without SUD . More intensive treatment is most likely needed for MDD patients with both drug and alcohol use disorders
After having corrected for these apparent mistakes , we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age ; while this suggests SSRIs to be safe drugs in the non-elderly , they do confirm what is already known , that is , that they may enhance the risk for SAEs in the old .
According to a systematic review on the use of selective serotonin reuptake inhibitors ( SSRIs ) in adult depression that was recently published in BMC Psychiatry , the results of which have been widely disseminated in lay media , these drugs increase the risk for serious adverse events ( SAEs ) while exerting poor antidepressant efficacy .