***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To assess the efficacy and safety of aripiprazole versus placebo as adjunctive treatment to st and ard antidepressant therapy ( ADT ) in patients with major depressive disorder ( MDD ) who showed an incomplete response to 1 prospect i ve and 1 to 3 historical courses of ADT within the current episode . METHOD The study comprised a 7- to 28-day screening phase , an 8-week prospect i ve treatment phase , and a 6-week double-blind treatment phase . Patients with DSM-IV-TR-defined MDD were enrolled between June 16 , 2004 , and April 27 , 2006 . During prospect i ve treatment , patients received ADT : escitalopram , fluoxetine , paroxetine controlled-release , sertraline , or venlafaxine extended-release , each with single-blind , adjunctive placebo . Incomplete responders continued ADT and were r and omly assigned to double-blind , adjunctive placebo or adjunctive aripiprazole ( 2 - 15 mg/day with fluoxetine or paroxetine ; 2 - 20 mg/day with all others ) . The primary efficacy endpoint was the mean change from end of prospect i ve treatment to end of double-blind treatment ( week 14 , last observation carried forward ) in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score ( analysis of covariance ) . RESULTS A total of 178 patients were r and omly assigned to adjunctive placebo and 184 to adjunctive aripiprazole . Baseline demographics were similar between groups ( mean MADRS total score of 26.0 ) . Mean change in MADRS total score was significantly greater with adjunctive aripiprazole ( -8.8 ) than adjunctive placebo ( -5.8 ; p < .001 ) . Adverse events ( AEs ) that occurred in > or = 10 % of patients with adjunctive placebo or adjunctive aripiprazole were akathisia ( 4.5 % vs. 23.1 % ) , headache ( 10.8 % vs. 6.0 % ) , and restlessness ( 3.4 % vs. 14.3 % ) . Discontinuations due to AEs were low with adjunctive placebo ( 1.7 % ) and adjunctive aripiprazole ( 2.2 % ) ; only 1 adjunctive aripiprazole-treated patient discontinued due to akathisia . CONCLUSIONS In patients with MDD who showed an incomplete response to ADT , adjunctive aripiprazole was efficacious and well tolerated . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00095823 BACKGROUND Previous reports have suggested that lamotrigine is effective as an antidepressant augmentation agent in patients with treatment-resistant unipolar depression . This study is the largest double-blind placebo-controlled study conducted to date of lamotrigine in this role . METHOD In this multicenter trial , conducted at 19 sites , patients aged 18 - 65 years with a DSM-IV/ICD-10 diagnosis of unipolar , nonpsychotic major depressive disorder ( confirmed by the Mini-International Neuropsychiatric Interview ) who had failed at least 1 adequate trial of an antidepressant ( N = 183 ) were first treated for 8 weeks with open-label paroxetine or paroxetine controlled-release in dosages up to 50 mg/d or 62.5 mg/d , respectively . Individuals with a 17-item Hamilton Depression Rating Scale ( HDRS-17 ) score ≥ 15 ( n = 96 ) were then r and omized on a double-blind basis to receive either placebo or lamotrigine in dosages titrated upward to a maximum of 400 mg/d for 10 weeks . Sixty-five patients completed the study . The primary outcome measure was the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the main secondary outcome measures were the HDRS-17 and Clinical Global Impressions-Severity of Illness ( CGI-S ) and Clinical Global Impressions-Improvement ( CGI-I ) ratings . Data were collected from 2003 to 2006 . RESULTS Results of the primary efficacy analysis of the r and omized patients using the MADRS , HDRS-17 , CGI-S , and CGI-I did not demonstrate a statistically significant difference between lamotrigine and placebo groups , although some secondary analyses were suggestive of efficacy , particularly in those patients who completed the study ( completer analysis ) and in more severely ill patients ( HDRS-17 ≥ 25 ) . CONCLUSIONS This add-on study of patients with treatment-resistant depression failed to detect a statistically significant difference between lamotrigine and placebo given for 10 weeks . However , post hoc analyses suggest that future studies of lamotrigine 's efficacy might focus on specific subgroups with depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00901407 BACKGROUND This phase 2 study examined the efficacy and tolerability of edivoxetine , a highly selective norepinephrine reuptake inhibitor , as an adjunctive treatment for patients with major depressive disorder ( MDD ) who have a partial response to selective serotonin reuptake inhibitor ( SSRI ) treatment . METHODS Study design consisted of double-blind , 10-week therapy of adjunctive edivoxetine ( 6 - 18 mg once daily ) or adjunctive placebo with SSRI .  Inclusion /entry criteria included partial response to current SSRI by investigator opinion and a GRID 17-item Hamilton Rating Scale for Depression ( HAMD17 ) total score ≥16 . The primary efficacy measure was the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Safety measures included treatment-emergent adverse events ( TEAE ) and vital signs . RESULTS For the primary evaluable population ( n=63 for adjunctive edivoxetine and n=68 for adjunctive placebo ) , the treatment groups did not differ significantly on the primary outcome of change from baseline to week 8 in the MADRS total score ; the effect size of edivoxetine treatment was 0.26 . Significant treatment differences , favoring adjunctive edivoxetine ( p≤.05 ) , were shown for improvements in role functioning and the functional impact of fatigue . For the adjunctive edivoxetine r and omized group ( N=111 ) , the most frequent TEAEs were hyperhidrosis ( 7.2 % ) , nausea ( 7.2 % ) , erectile dysfunction ( 6.3 % ) and testicular pain ( 6.3 % ) . Hemodynamic changes were observed in blood pressure and pulse rate between treatment groups . LIMITATIONS Study was underpowered for an alpha 2-sided 0.05 significance level for the primary outcome . CONCLUSIONS For patients with MDD who had a partial response to SSRIs  , adjunctive edivoxetine treatment was not statistically superior to adjunctive placebo on the primary outcome measure . However , pending further study , improved functioning and remission rate suggest a potential role for edivoxetine for patients with depression BACKGROUND The efficacy , safety , and tolerability of lisdexamfetamine dimesylate ( LDX ) augmentation of antidepressant monotherapy in adults with major depressive disorder ( MDD ) from two phase 3 studies are reported . METHODS Across study 1 (  placebo  , n=201 ; LDX , n=201 ) and study 2 ( placebo , n=213 ; LDX , n=211 ) , most participants ( placebo and LDX ) in the safety analysis set were female ( study 1 : 66.2 % and 64.2 % ; study 2 : 67.1 % and 66.8 % ) ; mean±SD ages were 41.8±12.04 with placebo and 42.2±12.32 with LDX in study 1 and 42.6±11.41 with placebo and 42.0±11.63 with LDX in study 2 . Participants ( 18 - 65 y ) had DSM-IV-TR-diagnosed MDD and lead-in baseline Montgomery-Åsberg Depression Rating Scale ( MADRS ) total scores ≥24 . Eight-week antidepressant lead-in phases prospect ively assessed antidepressant response . Then , 8 weeks of r and omized ( 1:1 ) , double-blind treatment with dose-optimized LDX ( 20 - 70 mg ) or placebo in participants exhibiting inadequate antidepressant monotherapy responses ( augmentation baseline MADRS total scores ≥18 and < 50 % MADRS total score reductions from lead-in baseline to augmentation baseline ) was initiated . The primary endpoint was MADRS total score change from augmentation baseline to week 16 . Safety and tolerability measures included the occurrence of treatment-emergent adverse events ( TEAEs ) . RESULTS Least squares mean ( 95 % CI ) treatment differences ( LDX-placebo ) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 ( 0.1 [ -1.7 , 2.0 ] , P=0.883 ) or study 2 ( -0.5 [ -2.3 , 1.3 ] , P=0.583 ) . The only TEAE reported by > 5 % of LDX participants at twice the placebo rate in both studies was dry mouth . LIMITATIONS Limitations include the exclusion of participants with psychiatric comorbidities/active medical disorders , the inability to assess specific MDD symptom domains ( eg , anhedonia , cognition ) or subtypes , the use of telephone-based depression assessment s , and the potential influence of placebo response . CONCLUSION Contrary to expectations , LDX augmentation was not superior to placebo in reducing depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy Introduction Efficacy of depression treatments , including adjunctive antipsychotic treatment , has not been explored for patients with worsening symptoms after antidepressant therapy ( ADT ) . Methods This post-hoc analysis utilized pooled data from 3 similarly design ed , r and omized , double-blind , placebo-controlled trials that assessed the efficacy , safety , and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT . The studies had 2 phases : an 8-week prospect i ve ADT phase and 6-week adjunctive ( aripiprazole or placebo ) treatment phase . This analysis focused on patients whose symptoms worsened during the prospect i ve 8-week ADT phase ( worsening defined as > 0 % increase in Montgomery – Åsberg Depressive Rating Scale [ MADRS ] Total score ) . During the 6-week , double-blind , adjunctive phase , response was defined as ≥50 % reduction in MADRS Total score and remission as ≥50 % reduction in MADRS Total score and MADRS score ≤10 . Results Of 1065 patients who failed to achieve a response during the prospect i ve phase , 160 exhibited worsening of symptoms ( ADT-Worseners ) , and 905 exhibited no change/reduction in MADRS scores ( ADT-Non-worseners ) . Response rates for ADT-Worseners at endpoint were 36.6 % ( adjunctive aripiprazole ) and 22.5 % ( placebo ) . Similarly , response rates at endpoint for ADT-Non-worseners were 37.5 % ( adjunctive aripiprazole ) and 22.5 % ( placebo ) . Remission rates at endpoint for ADT-Worseners were 25.4 % ( adjunctive aripiprazole ) and 12.4 % ( placebo ) . For ADT-Non-worseners , remission rates were 29.9 % ( adjunctive aripiprazole ) and 17.4 % ( placebo ) . Conclusion These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy . The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT OBJECTIVE This r and omized , placebo-controlled study evaluated the efficacy and safety of a fixed dose ( 3mg/day ) and flexible dose ( 3 - 15 mg/day ) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy ( ADT ) . METHOD During an 8-week prospect i ve treatment phase , patients experiencing a major depressive episode received clinicians ' choice of ADT . Subjects with inadequate response to ADT were r and omized to receive adjunctive treatment with placebo ( n=195 ) , fixed dose aripiprazole ( n=197 ) or flexible dose aripiprazole ( n=194 ) for 6 weeks . The primary efficacy endpoint was mean change in the Montgomery-Åsberg Depression Rating Scale ( MADRS ) total score from the end of prospect i ve treatment ( baseline ) to the end of r and omized treatment . RESULTS More than 90 % of patients in all treatment groups completed the 6-week double-blind treatment phase . Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole ( -10.5 and -9.6 , respectively ) than with placebo ( -7.4 ) . Arip 
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Thus , where a benefit was observed on the SDS total or mean , this was generally driven by improvement on the " social life " and " family life " items .
Conclusion The SDS , a self-rated functional measure , is informative in acute r and omized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT .
However , the item that measures work performance may be less relevant to this population than the items that measure social and family life