***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: The present study investigated possible clinical differences between bipolar patients with and without manic or hypomanic switch during antidepressant ( AD ) treatment .  The authors undertook a retrospective assessment of 169 individuals affected by bipolar disorder type I ( BP I : n=96 ) and II ( BP II : n=73 ) who experienced at least one manic or hypomanic episode following depression without any interposed normothymic period ( " manic switch " ) during AD therapy .  They were compared with a sex , age ( + /-5 years ) , and ethnicity-matched group of 247 subjects , r and omly selected from our pool of bipolar subjects who have never had manic switches . Only 2 of the 169 patients had had spontaneous switches before the AD-related one . Switched subjects were marginally older ( t=-2.65 , df=414 , P=.008 ) compared to not switched and less frequently delusional ( chi2=13.86 , P=.0002 ) . Polarity of the onset episode was more frequently depressive in switched patients ( chi2=21.93 , P=.00002 ) , which had also less previous manic episodes than not switched ( t=3.44 , df=332 , P=.0006 ) . Those differences were more pronounced in the BP I sub sample . Switched patients were more frequently BP I ( chi2=29.66 ; P<.00001 ) . Maintenance with mood stabilizers appears to be a strong protective factor ; in fact , of the 124 individuals undertaking a mood stabilizer therapy , 21 had a switch and 103 had no switches ( chi2=41.10 , P<.000001 ) . In conclusion , some clinical variables , such as the number of manic episodes , the presence of delusions , the polarity of onset episode , and the mood-stabilizing treatment , may be involved in AD-related switches . Further studies are required to investigate the causal relationships between those factors BACKGROUND Adjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy . AIMS To examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression . METHOD Patients who were currently depressed despite taking lithium or valproate for at least 6 weeks were r and omised to treatment with agomelatine ( n = 172 )  or placebo ( n = 172 ) for 8 weeks of acute therapy and 44 weeks of continuation therapy ( trial registration : IS RCT N28588282 ) . RESULTS No significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery-Åsberg Depression Rating Scale scores from baseline to end-point . Adverse events including switches into mania/hypomania were low and similar in both groups . CONCLUSIONS Agomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression BACKGROUND Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression . AIMS To examine the relative acute effects of bupropion , sertraline and venlafaxine as adjuncts to mood stabilisers . METHOD In a 10-week trial , participants receiving out-patient treatment for bipolar disorder ( stratified for rapid cycling ) were r and omly treated with a flexible dose of one of the antidepressants , or their respective matching placebos , as adjuncts to mood stabilisers . RESULTS A total of 174 adults with bipolar disorder I , II or not otherwise specified , currently in the depressed phase , were included . All three antidepressants were associated with a similar range of acute response ( 49 - 53 % ) and remission ( 34 - 41 % ) . There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline . CONCLUSIONS More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression , especially if there is a prior history of rapid cycling OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of quetiapine and paroxetine monotherapy for major depression in bipolar disorder . METHOD 740 patients ( 478 bipolar I , 262 bipolar II ) with major depressive episodes ( DSM-IV ) were r and omly assigned to quetiapine 300 mg/d ( n = 245 ) , quetiapine 600 mg/d ( n = 247 ) , paroxetine 20 mg/d ( n = 122 ) , or placebo ( n = 126 ) for 8 weeks . The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score . The study was conducted from May 2005 to May 2007 . RESULTS Mean MADRS score change from baseline at 8 weeks was -16.19 for quetiapine 300 mg , -16.31 for quetiapine 600 mg , -13.76 for paroxetine , and -12.60 for placebo ( P < .001 for both quetiapine doses , P = .313 for paroxetine , vs placebo ) . Quetiapine-treated ( both doses ) , but not paroxetine-treated , patients showed significantly greater improvements ( P < or = .05 ) in most secondary outcomes measures at week 8 versus the placebo group . Paroxetine significantly improved Hamilton Anxiety Rating Scale scores versus placebo ( P < .05 ) but not MADRS or Hamilton Depression Rating Scale ( HDRS ) scores . Both quetiapine doses were associated with greater improvements than paroxetine for MADRS and HDRS scores . The most common adverse events were dry mouth , somnolence , sedation , and dizziness with quetiapine ( both doses ) and dry mouth , sedation , headache , insomnia , and nausea with paroxetine . The incidence of treatment-emergent mania/hypomania was lower with quetiapine compared with paroxetine and placebo . CONCLUSIONS Quetiapine ( 300 or 600 mg/d ) , but not paroxetine , was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder . Quetiapine treatment was generally well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00119652 BACKGROUND Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression . METHOD The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale . Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age , sex , diagnosis ( DSM-IV bipolar I vs. bipolar II ) , number of previous manic episodes , type of antidepressant therapy used ( electroconvulsive therapy vs. antidepressant drugs and , more particularly , selective serotonin reuptake inhibitors [ SSRIs ] ) , use and type of mood stabilizers ( lithium vs. anticonvulsants ) , and temperament of the patient , assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview . RESULTS Switches to hypomania or mania occurred in 27 % of all patients ( N = 12 ) ( and in 24 % of the subgroup of patients treated with SSRIs [ 8/33 ] ) ; 16 % ( N = 7 ) experienced manic episodes , and 11 % ( N = 5 ) experienced hypomanic episodes . Sex , age , diagnosis ( bipolar I vs. bipolar II ) , and additional treatment did not affect the risk of switching . The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer . In contrast , mood switches were less frequent in patients receiving lithium ( 15 % , 4/26 ) than in patients not treated with lithium ( 44 % , 8/18 ; p = .04 ) . The number of previous manic episodes did not affect the probability of switching , whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching ( p = .008 ) . CONCLUSION The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment . Particular attention should be paid to patients with a hyperthymic temperament , who have a greater risk of mood switches To determine the efficacy and tolerability of olanzapine/fluoxetine combination ( OFC ) compared with lamotrigine ( Lam ) for long-term treatment of bipolar I depression , this 25-wk , r and omized , double-blind study compared OFC ( 6/25 , 6/50 , 12/25 , or 12/50 mg/d , n=205 ) with Lam titrated to 200 mg/d ( n=205 ) in patients with bipolar I disorder , depressed . A protocol -specified analysis of 7-wk outcomes was previously reported . Outcome measures included Clinical Global Impressions-Severity of Illness ( CGI-S ) ( primary ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , and Young Mania Rating Scale ( YMRS ) scores .  OFC-treated patients had significantly greater improvement than Lam-treated patients over 25 wk on CGI-S ( p=0.008 ) , MADRS ( p=0.005 ) , and YMRS ( p<0.001 ) scores , and from baseline across visits from week 5 ( titration complete ) to the end of the study on CGI-S ( p=0.043 ) , MADRS ( p=0.017 ) , and YMRS ( p=0.001 ) scores . Of patients in remission after the 7-wk acute phase , there was no significant difference between treatment groups in the incidence of relapse ( MADRS > 15 , p=0.528 ) . Rate of treatment-emergent mania was not significantly different by treatment ( p=0.401 ) . OFC-treated patients had more frequent ( p<0.05 ) somnolence , increased appetite , dry mouth , sedation , weight gain , and tremor ;  Lam-treated patients had more frequent insomnia . There was a significant difference in incidence of treatment-emergent cholesterol > or = 240 ( p<0.001 ) and in weight gain of > or = 7 % ( p<0.001 ) in favour of the Lam group . Patients with bipolar I depression had significantly greater symptom improvement over 25 wk on OFC compared with Lam . There was no treatment difference in incidence of relapse .  OFC-treated patients had more treatment-emergent adverse events and greater incidence of weight gain and hypercholesterolaemia OBJECTIVES Agomelatine has been shown to be safe and efficient in the treatment of major depressive disorder at 25 mg daily . The aim of this study was to gather preliminary data regarding the antidepressant efficacy of agomelatine in patients with bipolar I disorder experiencing a major depressive episode . METHODS Bipolar I patients on lithium ( n = 14 ) or valpromide ( n = 7 ) , with a Hamilton Rating Scale for Depression ( HAM-D-17 ) total score > or = 18 , were given adjunctive open-label agomelatine at 25 mg/day for a minimum of 6 weeks followed by an optional extension of up to an additional 46 weeks . RESULTS Using intent-to-treat data , 81 % of patients met criteria for marked improvement ( > 50 % improvement from baseline in HAM-D score ) at study endpoint . Patients were severely depressed at study entry ( HAM-D of 25.2 ) and 47.6 % responded as early as at one week of treatment . Nineteen patients entered the optional extension period for a mean of 211 days ( range 6 - 325 days ) . Eleven patients completed the one-year extension on agomelatine . There were no dropouts due to adverse events during the acute phase of treatment ( 6 weeks ) . Six patients experienced serious adverse events during the one-year period . Three lithium-treated patients experienced manic or hypomanic episodes during the optional extension period , one of which was treatment-related . CONCLUSIONS These results indicate the effectiveness of agomelatine 25 mg in the treatment of depressed bipolar I patients co-medicated with lithium or valpromide . A r and omized controlled trial is planned to confirm these results OBJECTIVES Current guidelines for the initial treatment of bipolar type II ( BP II ) major depressive episode ( MDE ) recommend using either a mood stabilizer alone or a combination of a mood stabilizer plus a selective serotonin re-uptake inhibitor ( SSRI ) . This recommendation is the result of concern over antidepressant-induced manic switch episodes . However , recent evidence suggests that the manic switch rate may be low in BP II MDE during SSRI therapy . METHODS As part of a r and omized 
    Output:
    
Overall , concurrent lithium therapy predicted the lowest TEM rates .
Rates of TEM vary primarily depending on study setting , which is concordant with the high degree of heterogeneity of the included records .