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
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
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 .