Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. A controlled trial of antidepressants in patients with Parkinson disease and depression Does Nefazodone Improve Both Depression and Parkinson Disease? A Pilot Randomized Trial A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease Sertraline for the treatment of depression in Parkinson's disease. SSRIs Do Not Worsen Parkinson's Disease: Evidence from an Open-Label, Prospective Study GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol Antidepressant Class, Age, and the Risk of Deliberate Self-Harm: A Propensity Score Matched Cohort Study of SSRI and SNRI Users in the USA Combination of inositol and serotonin reuptake inhibitors in the treatment of depression Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model. Response to an open trial of a second SSRI in major depression. Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder 5-HTTLPR modulates antidepressant efficacy in depressed women Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline Clinical and Neurobiological Effects of Tianeptine and Paroxetine in Major Depression Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women's Health Initiative study. Severity of depression and response to antidepressants: GENPOD randomised controlled trial. Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors.
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 : Parkinson disease ( PD ) is a common neurodegenerative disease affecting up to 1 million individuals in the United States . Depression affects up to 50 % of these patients and is associated with a variety of poor outcomes for patients and their families . Despite this , there are few evidence -based data to guide clinical care . Methods : An NIH-funded , r and omized , controlled trial of paroxetine CR , nortriptyline , and placebo in 52 patients with PD and depression . The primary outcomes were the change in the Hamilton Depression Rating Scale ( HAM-D ) and the percentage of depression responders at 8 weeks . Results : Nortriptyline was superior to placebo for the change in HAM-D ( p < 0.002 ) ; paroxetine CR was not . There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks ( p < 0.079 ) . Response rates favored nortriptyline ( p = 0.024 ) : nortriptyline 53 % , paroxetine CR 11 % , placebo 24 % . In planned contrasts of response rates , nortriptyline was superior to paroxetine CR ( p = 0.034 ) . Nortriptyline was also superior to placebo in many of the secondary outcomes , including sleep , anxiety , and social functioning , while paroxetine CR was not . Both active drug treatments were well tolerated . Conclusions : Though relatively modest in size , this is the largest placebo-controlled trial done to date in patients with Parkinson disease ( PD ) and depression .  Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not . When compared directly , nortriptyline produced significantly more responders than did paroxetine CR . The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors . ARR = absolute risk reduction ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , 4th edition ; HAM-A = Hamilton Anxiety Scale ; HAM-D = Hamilton Depression Rating Scale ; MMSE = Mini-Mental State Examination ; NNT = number needed to treat ; PD = Parkinson disease ; PDQ = Parkinson ’s Disease Question naire ; PSQI = Pittsburgh Sleep Quality Index ; SCID = Structured Clinical Interview ; SSRI = selective serotonin reuptake inhibitor ; TCA = tricyclic antidepressant ; UPDRS = Unified Parkinson ’s Disease Rating Scale Some of the selective serotonin reuptake inhibitors (SSRI)-induced motor side effects are mediated by stimulating 5-HT2 receptors in the basal ganglia , probably because serotonin inhibits the subsequent neuronal dopamine release . We hypothesized that nefazodone , a serotonin 2 antagonist/reuptake inhibitor ( SARI ) that selectively blocks 5-HT2 receptors , could disrupt the aforementioned inhibitory pathway . Therefore , increased dopamine levels in the postsynaptic milieu and an improvement in the motor symptoms in depressed patients with Parkinson disease ( PD ) should be observed . This study was design ed to determine whether nefazodone has a dual activity as an antidepressant and as an agent capable of reducing the extrapyramidal symptoms in depressed parkinsonian patients . Depressed patients with PD were r and omly assigned to 2 therapeutic groups : nefazodone or fluoxetine . Patients were evaluated by a psychiatrist and were blindly assessed by a neurologist with an array of scales . Patients on nefazodone ( n = 9 ) showed a significant improvement over time in the total Unified Parkinson Disease Rating Scale score ( UPDRS ) ( part II + part III ) ( P = 0.004 ) and in the UPDRS subscore part III ( P = 0.003 ) . None of these scores changed over time in the fluoxetine group ( n = 7 ) . Both , nefazodone and fluoxetine were equally effective as antidepressants : Beck Depression Inventory scores significantly improved ( P < 0.001 ) , with no significant differences between treatment groups ( P = 0.97 ) . If our results can be confirmed in a larger clinical trial , nefazodone ought to be considered over fluoxetine given its secondary beneficial effects regarding the reduction of extrapyramidal symptoms in depressed PD patients Objective : To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor ( SSRI ) and a serotonin and norepinephrine reuptake inhibitor ( SNRI ) in the treatment of depression in Parkinson disease ( PD ) . Methods : A total of 115 subjects with PD were enrolled at 20 sites . Subjects were r and omized to receive an SSRI ( paroxetine ; n = 42 ) , an SNRI ( venlafaxine extended release [ XR ] ; n = 34 ) , or placebo ( n = 39 ) . Subjects met DSM-IV criteria for a depressive disorder , or operationally defined subsyndromal depression , and scored > 12 on the first 17 items of the Hamilton Rating Scale for Depression ( HAM-D ) . Subjects were followed for 12 weeks ( 6-week dosage adjustment , 6-week maintenance ) . Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR . The primary outcome measure was change in the HAM-D score from baseline to week 12 . Results : Treatment effects ( relative to placebo ) , expressed as mean 12-week reductions in HAM-D score , were 6.2 points ( 97.5 % confidence interval [ CI ] 2.2 to 10.3 , p = 0.0007 ) in the paroxetine group and 4.2 points ( 97.5 % CI 0.1 to 8.4 , p = 0.02 ) in the venlafaxine XR group . No treatment effects were seen on motor function . Conclusions : Both paroxetine and venlafaxine XR significantly improved  depression in subjects with PD . Both medications were generally safe and well tolerated and did not worsen motor function . Classification of Evidence : This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD Although antidepressant medications are commonly used to treat depression in Parkinson 's disease ( PD ) , little information is available regarding their safety and efficacy in this condition . Sertraline is a relatively selective serotonin reuptake inhibitor with some dopamine reuptake inhibitor activity . It has a favorable tolerability profile , especially in the elderly . We undertook an open-label pilot evaluation of the safety and efficacy of sertraline to treat depression in PD . A total of 15 patients with PD and depression participated in the study .  Sertraline was introduced at a daily dose of 25 mg for 1 week and then increased to 50 mg/day . Patients underwent evaluation at baseline and at a final visit approximately 7 weeks later . Sertraline was generally well tolerated , but five patients experienced side effects , and two discontinued medication . Patients taking selegiline experienced more adverse effects . Beck Depression Inventory scores improved significantly ( mean + /- SE = 16.0 + /- 2.0 vs 11.7 + /- 1.9 , p = 0.03 ) , and Unified Parkinson 's Disease Rating Scale and energy-level scores were unchanged . These results suggest that sertraline may be a useful treatment for depression in PD . As substantial placebo effects can occur in studies of PD and depression , placebo-controlled , double-blind studies are warranted Selective serotonin reuptake inhibitors ( SSRIs ) have been reported to be useful in the treatment of  depression in patients with Parkinson 's disease ( PD ) . However , a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs . So far , no prospect i ve trial comparing the effects of different SSRIs in depressed patients with PD has been performed . The aim of the present study was to assess the effects of four SSRIs ( citalopram , fluoxetine , fluvoxamine , and sertraline ) on motor performance and their efficacy on depression in a group of patients with PD . Sixty-two consecutive nondemented , nonfluctuating , depressed patients with PD were included in four treatment groups ( 15 patiens received citalopram , 16 fluoxetine , 16 fluvoxamine , and 15 sertraline ) . The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Beck Depression Inventory , and Hamilton Depression Rating Scale at baseline and after 1 , 3 , and 6 months . Fifty-two patients completed the study .  UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied . A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs ( Beck and Hamilton scores improving;p < 0.05 according to an analysis of variance ) . Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD 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 Background The US Food and Drug Administration ’s meta-analyses of placebo-controlled antidepressant trials found approximately twice the rate of suicidal behaviors among children and adults aged 24 years and younger who were r and omized to receive antidepressant medication  than among those who were r and omized to placebo .  Rates of suicidal behavior were similar for subjects aged 25–64 years whether they received antidepressants or placebo , and subjects aged 65 years or older r and omized to antidepressants were found to have lower rates of suicidal behavior . The age-stratified FDA meta-analyses did not have adequate power to investigate rates of suicidal behaviors by antidepressant drug class . Objective Our objective was to assess the risk of deliberate self-harm associated with the two most commonly prescribed classes of antidepressant agents . Design Propensity score matched cohort study of incident users of antidepressant agents . Setting Population -based healthcare utilization data of US residents . Patients US residents aged 10–64 years with a recorded diagnosis of depression who initiated use of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin norepinephrine reuptake inhibitors ( SNRIs ) between 1 January 1998 and 31 December 2010.Main Outcome Measures ICD-9 external cause of injury codes E950.x – E958.x ( deliberate self-harm ) . Results A total of 102,647 patients aged between 10 and 24 years , and 338,021 aged between 25 and 64 years , initiated therapy with antidepressants . Among 10–24 year olds , prior to propensity score matching , 75,675 initiated therapy with SSRIs and 5,344 initiated SNRIs . After matching , there were 5,344 SNRI users and 10,688 SSRI users . Among the older cohort , 36,037 SNRI users were matched to 72,028 SSRI users ( from an unmatched cohort of 225,952 SSRI initiators ) . Regardless of age cohort , patients initiating SSRIs and patients initiating SNRIs had similar rates of deliberate self-harm . Restriction to patients with no antidepressant use in the past 3 years did not alter our findings . Conclusions Our findings of similar rates of deliberate self-harm for depressed patients who initiate treatment with either an SSRI or an SNRI suggests that physicians who have decided that their patients would benefit from initiating antidepressant therapy need not weigh differential suicide risk when deciding which class of antidepressant to prescribe 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 BACKGROUND An estimated 30 % to 40 % of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors ( SSRIs ) and the period in which treatment efficacy can be assessed is relatively long . Therefore , a test to identify potential nonresponders could be useful in the treatment of depression . Serotonin transporter gene ( SLC6A4 ) variations have been reported to account for differences in the way individuals respond to SSRI treatment . OBJECTIVE A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR , a polymorphism of the SLC6A4 genotype , could be an efficient tool in the treatment of depression . METHODS A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherl and s with an alternative strategy for the treatment of depression . Under treatment guidelines in The Netherl and s , all patients with depression receive SSRI treatment ( nontesting strategy ) . Under the alternative strategy , genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment ( genetic testing strategy ) . Probabilities ( predicted results ) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology . To test the robustness of the model , 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion . Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs , serotonin-norepinephrine reuptake inhibitors ( SNRIs ) , and tricyclic antidepressants ( TCAs ) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred . RESULTS When genetic testing was performed before an antidepressant was prescribed , 64.6 % of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0 % of patients who did not receive genetic testing . After 12 weeks , 79.5 % of patients in the testing group who received an SNRI as initial treatment and 83.2 % of those who received a TCA initially were predicted to be in remission compared with 76.7 % of patients in the nontesting group . Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges . However , these findings were based on a theoretic model and did not include cost assessment . Pretreatment genetic testing must be evaluated further in r and omized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended . CONCLUSIONS The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment BACKGROUND We evaluated the efficacy of a second serotonin selective reuptake inhibitor ( SSRI ) in patients who had failed to respond to the first SSRI used . METHOD Fifty-five patients with major depression who had failed one of the SSRIs for their current depressive episode were included . After failing a trial of one SSRI , they received a second SSRI in an open clinical trial . RESULTS On the basis of the Clinical Global Impression-Improvement scale , 28 of 55 patients had a marked or complete antidepressant response . CONCLUSION These data provide preliminary clinical evidence that substituting a second SRI may be a useful clinical alternative in depressed patients who fail to respond to an adequate trial of an SSRI The effects of treatment with serotonin ( 5-HT ) reuptake inhibitors on platelet 5-HT2 receptors , 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors ( SSRI ) , paroxetine , and fluoxetine , for the treatment of major depression . Hamilton Depression Rating Scale ( HAM-D ) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline , after 4 and 8 weeks of treatment , and were compared to 21 healthy controls . Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites , labelled with [3H]paroxetine , or 5-HT2 receptors , labelled with [3H]LSD . However , a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline . A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls . Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively . These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation . Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy , particularly in suicidal depressed patients 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 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 BACKGROUND Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters . We wished to investigate whether genetic variation could be used to target or personalise treatment , in a comparison of selective serotonin reuptake inhibitors ( SSRIs ) with noradrenaline reuptake inhibitors ( NARIs ) . AIMS To test the hypothesis that patients homozygous for the long ( insertion ) polymorphism of the serotonin transporter ( 5-HTTLPR ) have an increased response to SSRI antidepressants but not to NARI antidepressants . METHOD In an individually r and omised , parallel-group controlled trial , people meeting criteria for a depressive episode who were referred by their general practitioner were r and omised to receive either citalopram ( an SSRI ) or reboxetine ( an NARI ) . R and omisation was by means of a remote automated system accessed by telephone . The main outcome was depressive symptoms , measured by Beck Depression Inventory ( BDI ) total score 6 weeks after r and omisation . The trial was registered with the International St and ard R and omised Controlled Trials Number registry ( IS RCT N31345163 ) . RESULTS Altogether 298 participants were r and omised to receive citalopram and 303 were r and omised to reboxetine . At 6 weeks follow-up , complete data were available for 258 participants taking citalopram and 262 taking reboxetine . We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment . The interaction term for BDI score at 6 weeks was 0.50 ( 95 % CI -2.04 to 3.03 , P = 0.70 ) , which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype . CONCLUSIONS It is unlikely that the 5-HTTLPR polymorphism alone will be clinical ly useful in predicting response to antidepressants in people with depression BACKGROUND The cost-effectiveness of tricyclic antidepressants ( TCAs ) and selective serotonin reuptake inhibitors ( SSRIs ) has not been compared in a prospect i ve study in primary care . AIMS To determine the relative cost-effectiveness of TCAs , SSRIs and lofepramine in UK primary care . METHOD An open-label , three-arm r and omised trial with a preference arm . Practitioners referred 327 patients with incident depression . RESULTS No significant differences were found in effectiveness or cost-effectiveness . The numbers of depression-free weeks over 12 months ( on the Hospital Anxiety and Depression Scale ) were 25.3 ( 95 % CI 21.3 - 29.0 ) for TCAs , 28.3 ( 95 % CI 24.3 - 32.2 ) for SSRIs and 24.6 ( 95 % CI 20.6 - 28.9 ) for lofepramine .  Mean health service costs per patient were pound 762 ( 95 % CI 553 - 1059 ) for TCAs , pound 875 ( 95 % CI 675 - 1355 ) for SSRIs and pound 867 ( 95 % CI 634 - 1521 ) for lofepramine .  Cost-effectiveness acceptability curves suggested SSRIs were most cost-effective ( with a probability of up to 0.6 ) . CONCLUSIONS The findings support a policy of recommending SSRIs as first-choice antidepressants in primary care BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy 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 Antidepressants are commonly prescribed medications , but their effect on cardiovascular morbidity and mortality remains unclear . METHODS Prospect i ve cohort study of 136 293 community-dwelling postmenopausal women in the Women 's Health Initiative ( WHI ) . Women taking no antidepressants at study entry and who had at least 1 follow-up visit were included . Cardiovascular morbidity and all-cause mortality for women with new antidepressant use at follow-up ( n = 5496 ) were compared with those characteristics for women taking no antidepressants at follow-up ( mean follow-up , 5.9 years ) . RESULTS Antidepressant use was not associated with coronary heart disease ( CHD ) .  Selective serotonin reuptake inhibitor ( SSRI ) use was associated with increased stroke risk ( hazard ratio [HR],1.45 , [ 95 % CI , 1.08 - 1.97 ] ) and all-cause mortality ( HR,1.32 [ 95 % CI , 1.10 - 1.59 ] ) . Annualized rates per 1000 person-years of stroke with no antidepressant use and SSRI use were 2.99 and 4.16 , respectively , and death rates were 7.79 and 12.77 . Tricyclic antidepressant ( TCA ) use was associated with increased risk of all-cause mortality ( HR,1.67 [ 95 % CI , 1.33 - 2.09 ] ; annualized rate , 14.14 deaths per 1000 person-years ) . There were no significant differences between SSRI and TCA use in risk of any outcomes . In analyses by stroke type , SSRI use was associated with incident hemorrhagic stroke ( HR , 2.12 [ 95 % CI , 1.10 - 4.07 ] ) and fatal stroke ( HR , 2.10 [ 95 % CI , 1.15 - 3.81 ] ) . CONCLUSIONS In postmenopausal women , there were no significant differences between SSRI and TCA use in risk of CHD , stroke , or mortality . Antidepressants were not associated with risk of CHD .  Tricyclic antidepressants and SSRIs may be associated with increased risk of mortality , and SSRIs with increased risk of hemorrhagic and fatal stroke , although absolute event risks are low . These findings must be weighed against quality of life and established risks of cardiovascular disease and mortality associated with untreated depression BACKGROUND Antidepressant prescribing is widespread . Nonetheless , response to antidepressants is variable . If it was possible to predict response to medication and thus tailor treatment accordingly , this would not only improve patient outcomes but may also have economic benefits . AIMS To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors ( NARIs ) than selective serotonin reuptake inhibitors ( SSRIs ) compared with individuals with less severe depression . METHOD Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory ( BDI ) were r and  omised to either an SSRI ( citalopram 20 mg daily ) or a NARI ( reboxetine 4 mg twice daily ) . R and omisation was by means of a remote automated telephone system . The main outcome was depressive symptoms measured by the BDI total score 6 weeks after r and omisation . ( TRIAL REGISTRATION IS RCT N31345163 . ) RESULTS In total , 601 participants were r and omised  ( citalopram : n = 298 , reboxetine : n = 303 ) . Ninety-one per cent were followed up at 6 weeks ( citalopram : n = 274 , reboxetine : n = 272 ) . There was little evidence to support an interaction between treatment and severity of depression ( interaction term : 0.02 , 95 % CI -0.59 to 0.62 , P = 0.96 ) . Adjustment for potential confounders ( age , gender , employment status , history of depression , number of life events and social support ) did not affect the findings ( interaction term : 0.06 , 95 % CI -0.54 to 0.66 , P = 0.85 ) . CONCLUSIONS Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care BACKGROUND Whether the Brain Derived Neurotrophic Factor ( BDNF ) Val66Met polymorphism can predict antidepressant drug efficacy in depressed patients remains unclear , suggesting that it may depend on antidepressant classes . We assessed the impact of Val66Met polymorphism on antidepressant response and remission depending on antidepressant classes . METHODS In a 6-month prospect i ve , real-world setting , treatment study , 345 Caucasian depressed patients requiring a new or different drug treatment with a selective serotonin reuptake inhibitor ( SSRI ) , a serotonin and noradrenalin reuptake inhibitor ( SNRI ) or a tricyclic antidepressant ( TCA )  , were genotyped and assessed for response and remission . RESULTS 231 ( 67 % ) patients were homozygous for the Val66 allele ( Val/Val ) and 114 ( 33 % ) were carriers of Met allele ( Met ) . 152 ( 44.1 % ) patients were treated with SSRI , the others with SNRI/TCA . Both response and remission were explained by interactions between the Val66Met polymorphism and antidepressant drug classes ( multivariate models adjusted for propensity-scores : p=0.02 and p=0.03 respectively ) . With SSRI , Val/Val patients had a higher response rate 3 months post-treatment than Met patients ( 68.1 % versus 44 % ; adjusted-OR : 3.04 , IC95 % [ 1.05 ; 9.37 ] , p=0.04 ) . With SNRI/TCA , Val/Val patients had a lower remission rate 6 months post-treatment than Met patients ( 33.3 % versus 60.9 % , adjusted-OR : 0.27 , IC95 % [ 0.09 ; 0.76 ] , p=0.02 ) . LIMITATIONS Limited sample size . CONCLUSIONS This study argues for a personalized prescription of antidepressants in Caucasian patients with major depressive disorder , based on the BDNF Val66Met polymorphism : SSRI should be preferred for Val/Val patients and SNRI/TCA for Met patients . Further studies are required to confirm these data BACKGROUND Selective serotonin reuptake inhibitors ( SSRIs ) and venlafaxine have been regarded as less toxic in overdose than tricyclic antidepressants ( TCAs ) . Within the TCAs , dothiepin has greater toxicity . Venlafaxine may be more toxic than SSRIs . AIM To assess the toxicity in overdose of venlafaxine and SSRIs compared to TCAs , and of dothiepin compared to other TCAs . DESIGN Cohort study of prospect ively collected data from the Hunter area , NSW , Australia . METHODS First admissions with antidepressant deliberate self-poisoning ( DSP ) ( November 1994 to April 2000 ) were identified ; the presence of seizures , life-threatening arrhythmias , coma , serotonin toxicity or ICU admission , and QRS duration were noted . RESULTS There were 538 admissions , with no deaths . The odds ratio ( OR ) for seizures with dothiepin vs. other TCAs was 3.4 ( 95%CI 1.2 - 9.9 ) . Seizures occurred in 7/51 ( 14 % ) venlafaxine overdoses ; all patients with seizures consumed > or = 900 mg . The OR for seizures vs. TCAs was 4.4 ( 95%CI 1.4 - 13.8 ) . Coma was less likely with venlafaxine and SSRIs . SSRIs , but not venlafaxine , were less likely to prolong the QRS to > or = 100 ms . ICU admission was less likely for SSRIs . Serotonin toxicity was much more common with venlafaxine and SSRIs . DISCUSSION Venlafaxine and dothiepin are pro-convulsant in overdose . Venlafaxine is more likely to cause serotonin toxicity , but less likely to cause coma than TCAs . SSRIs are less likely to cause coma , require ICU admission , or prolong the QRS , but are more likely to cause serotonin toxicity . Antidepressants other than TCAs or venlafaxine should be considered in patients at risk of seizure or suicide 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
An acceptability analysis showed that SSRIs were generally well tolerated .
Conclusions These results suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in PD .
Background Selective serotonin reuptake inhibitors ( SSRIs ) are the most commonly prescribed antidepressants for the treatment of depression in patients with Parkinson 's Disease ( PD ) but data on their efficacy are controversial .