***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 
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    Input: Background N-acetyl cysteine ( NAC ) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial . The current study aim ed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder . Method The efficacy of a double blind r and omized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined . Participants ( n = 149 ) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and , after eight weeks of open-label NAC treatment , were r and omized  to adjunctive NAC or placebo , in addition to treatment as usual . Participants ( primarily out patients ) were recruited through public and private services and through newspaper advertisements .  Time to intervention for a mood episode was the primary endpoint of the study , and changes in mood symptoms , functionality and quality of life measures were secondary outcomes . Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase . During the subsequent double-blind phase , there was minimal further change in outcome measures with scores remaining low . Consequently , from this low plateau , between-group differences did not emerge on recurrence , clinical functioning or quality of life measures . Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial ; however , these findings may be confounded by limitations .Trial Registration The trial was registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12607000074493 ) CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Introduction New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder ( BD ) . Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss . These changes have been hypothesised to result from chronic inflammation . The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline , a drug with neuroprotective and immune-modulating properties , and of aspirin , at doses expected to selectively inhibit cyclooxygenase 1 ( COX-1 ) . Methods and analysis 120 out patients between 18 and 55 years of age , who meet DSM-IV-TR criteria for BD ( type I or II ) and for a current major depressive episode will be recruited to take part in a r and omised , double-blind , placebo-controlled , parallel-group , proof-of-concept clinical trial following a 2 × 2 design . As adjuncts to existing treatment , subjects will be r and omised to receive one of the four treatment combinations : placebo-minocycline plus placebo-aspirin , active-minocycline plus placebo-aspirin , placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin . The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily , respectively . Antidepressant response will be evaluated by assessing changes in the Montgomery – Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial . As secondary outcome measures , the anti-inflammatory effects  of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines . Ethics and dissemination Minocycline has been widely used as an antibiotic in doses up to 400 mg/day . Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic . The study progress will be overseen by a Data , Safety and Monitoring Board , which will meet once every 6 months . Results of the study will be published in peer- review ed publications . Trial registration number Clinical Trials.gov : NCT01429272 OBJECTIVE To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder ( BD ) patients during depressive or mixed phases . METHODS We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication . Subjects were r and omized to receive 6 weeks of double-blind placebo or celecoxib ( 400 mg/day ) treatment . Current mood stabilizer or antipsychotic medication remained at the same doses during the trial . RESULTS Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale ( HamD ) scores after 1 week of treatment compared to the patients receiving placebo , but this difference was not statistically significant ( p = 0.09 ) . The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial ( p = 0.03 ) . The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial . Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash . CONCLUSIONS Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes BACKGROUND Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate , 2 effective treatments for bipolar disorder . The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder . METHODS A 4-month , double-blind , placebo-controlled study , comparing omega3 fatty acids ( 9.6 g/d ) vs placebo ( olive oil ) , in addition to usual treatment , in 30 patients with bipolar disorder . RESULTS A Kaplan-Meier survival analysis of the cohort found that the  omega3 fatty acid  patient group had a significantly longer period of remission than the placebo group ( P = .002 ; Mantel-Cox ) . In addition , for nearly every other outcome measure , the omega3 fatty acid group performed better than the placebo group . CONCLUSION Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder The aim of the present study was to assess the effect of aspirin on lithium‐related sexual dysfunction in men with stable bipolar affective disorder ( BAD ) BACKGROUND Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders , including bipolar disorder . This dysregulation may be amenable to therapeutic intervention . Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain , and the most generic of all endogenous antioxidants in terms of action . N-acetylcysteine ( NAC ) is a glutathione precursor that effectively replenishes brain glutathione . Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy , and the limited efficacy of mood stabilisers in the depressive phase of the disorder , this is a major unmet need . METHOD This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a r and omised  placebo controlled clinical trial of the efficacy of 1 g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder . RESULTS In this trial , the estimated mean baseline Bipolar Depression Rating Scale ( BDRS ) score was 19.7 ( SE=0.8 ) , and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 ( SE=0.8 ) . This reduction was statistically significant ( p<0.001 ) . Improvements in functioning and quality of life were similarly evident . CONCLUSION These open label data demonstrate a robust decrement in depression scores with NAC treatment . Large placebo controlled trials of acute bipolar depression are warranted Objective : Oxidative imbalance has emerged as a treatment target in bipolar disorder . As very limited data are available on the clinical use of antioxidants for mania , we report here results from a post hoc and exploratory subgroup analysis of a r and omized , placebo-controlled trial of N-acetyl cysteine ( NAC ) . Methods : This was a placebo-controlled , r and omized , clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania .  Symptomatic and functional outcomes were collected over the study period . Results : Fifteen participants were available for this report ; two participants in each group failed to complete all assessment s. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint . Conclusions : Although the sample size was small , these results indicated within-group efficacy for this glutathione precursor as compared to placebo . Future trials specifically design ed to demonstrate the efficacy of NAC in mania are needed OBJECTIVE To compare 2 omega-3 ( n-3 ) preparations enriched with eicosapentaenoic acid ( EPA ) versus docosahexaenoic acid ( DHA ) as monotherapy for major depressive disorder ( MDD ) in a 2-site , placebo-controlled , r and omized , double-blind clinical trial . METHOD 196 adults ( 53 % female ; mean [ SD ] age = 44.7 [ 13.4 ] years ) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale ( HDRS-17 ) score ≥ 15 were r and omized equally from May 18 , 2006 , to June 30 , 2011 , to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d , DHA-enriched n-3 1,000 mg/d , or placebo . RESULTS 154 subjects completed the study . Modified intent-to-treat ( mITT ) analysis ( n = 177 subjects with ≥ 1 postbaseline visit ; 59.3 % female , mean [ SD ] age 45.8 [ 12.5 ] years ) employed mixed-model repeated measures ( MMRM ) . All 3 groups demonstrated statistically significant improvement in the HDRS-17 ( primary outcome measure ) , 16-item Quick Inventory of Depressive Symptomatology-Self Report ( QIDS-SR-16 ) , and Clinical Global Improvement-Severity Scale ( CGI-S ) 
    Output:
    
Overall , a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression .