Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial Add-on Quetiapine for Bipolar Depression: A 12-Month Open-Label Trial Who will benefit from antidepressants in the acute treatment of bipolar depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q-learning Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder Antidepressant-associated switches from depression to mania in severe bipolar disorder. Long-term effectiveness of quetiapine in bipolar disorder in a clinical setting. Incidence and predictors of suicide attempts in bipolar I and II disorders: A 5‐year follow‐up study Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial. Course sequences in bipolar disorder: depressions preceding or following manias or hypomanias. Bupropion as an Add-on Therapy in Depressed Bipolar Disorder Type I Patients With Comorbid Cocaine Dependence A Consecutive Series of Treated Affected Offspring of Parents with Bipolar Disorder: Is Response Associated with the Clinical Profile? Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder Efficacy and mood conversion rate during long-term fluoxetine v. lithium monotherapy in rapid- and non-rapid-cycling bipolar II disorder. Online mindfulness-based intervention for late-stage bipolar disorder: pilot evidence for feasibility and effectiveness. A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Is Cognitive-Behavioural Therapy More Effective Than Psychoeducation in Bipolar Disorder? Efficacy of bright light therapy in bipolar depression A prospective open-label trial of extended-release carbamazepine monotherapy in children with bipolar disorder. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. A Pilot Study of Antidepressant-Induced Mania in Pediatric Bipolar Disorder: Characteristics, Risk Factors, and the Serotonin Transporter Gene Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial
Background We sought to test the hypothesis that antidepressants ( ADs ) may show preferential efficacy and safety among patients with type II bipolar disorder ( BD , BD-II ) more than patients with type I BD ( BD-I ) . Methods Patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , BD-I ( n = 21 ) and BD-II ( n = 49 ) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then r and omized openly to continue or discontinue ADs for up to 3 years . Outcomes were episode recurrences and changes in st and ardized symptom ratings . Results In follow-up averaging 1.64 years , both subgroups showed improvement in depressive episode frequency with AD continuation , but contrary to the hypothesis , more improvement was seen in BD-I than in BD-II ( for type II , mean [ st and ard deviation ] decrease in depressive episodes per year , 0.21 [ 0.26 ] ; for type I , mean ( SD ) decrease , 0.35 [ 0.15 ] ) . Subjects with BD-II who continued on ADs had slightly more depressive , but fewer manic/hypomanic , episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission . Conclusions The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I , except somewhat lower risk of manic/hypomanic episodes Objectives : Bipolar disorder ( BD ) is a disabling and often chronic condition . Patients with BD suffer from depression at least one-third of the time , but they do not always respond well to conventional mood stabilizers . Attempts to treat them with antidepressants can provoke a switch to mania or increased cycling . Our open-label trial aim ed to assess the long-term response of patients with bipolar depression to the addition of quetiapine to their usual treatment . Our study also sought to assess the safety and tolerability of quetiapine in patients with BD . Method : To meet inclusion criteria for the study , patients had a DSM-IV diagnosis of type I or II BD , were aged 18 years and older , currently suffered from depression with a score of > 18 on the Hamilton Depression Rating Scale ( HDRS ) , and had no change in antidepressant use for at least 3 weeks prior to the study . We added quetiapine to patients ' medication and attempted to increase the dosage to at least 400 mg daily . Outcome was measured at baseline and once monthly for 12 months on the HDRS , the Young Mania Rating Scale , the Clinical Global Impression Scale ( CGI ) , and the Abnormal Involuntary Movement Scale . Results : There were 19 patients enrolled in the study ( 6 men and 13 women ) , 2 of whom dropped out because they could not tolerate the drug . Seventeen completed at least 2 assessment s , and 7 patients completed the full 12-month trial . Data for the 17 patients ( that is , last observation carried forward ) at 12 months shows HDRS scores reduced from 27.2 to 12.1 and CGI scores reduced from 4.7 to 2.6 . Conclusions : Quetiapine seems to be helpful to and relatively well tolerated by patients with bipolar depression when it is added to their usual treatment . There is , however , a need for controlled trials Background There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders . Methods Traditional r and omized controlled trials and statistical methods are not design ed to discover if , when , and to whom an intervention should be applied ; thus , other method ological approaches are needed that allow for the practice of personalized , evidence -based medicine with patients with bipolar depression . Results Dynamic treatment regimes operationalize clinical decision-making as a sequence of decision rules , one per stage of clinical intervention , that map patient information to a recommended treatment . Using data from the acute depression r and omized care ( RAD ) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) study , we estimate an optimal dynamic treatment regime  via Q-learning . Conclusions The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a m and atory mood stabilizer Rationale Due to the episodic and chronic nature of bipolar disorder ( BD ) , maintenance therapy represents a critical part of treatment ; however , there is a paucity of studies comparing effectiveness of available long-term treatments . Objective The aim of this study is to determine and compare the efficacy of pharmacological treatments for maintenance treatment of BD by means of the number needed to treat ( NNT ) . Methods The efficacy of drugs used for maintenance treatment of BD , as emerging from the results of r and omized controlled trials , was assessed using the size effect measure of NNT . PubMed search es were conducted on English- language articles published until May 2010 using the search terms “ bipolar disorder , ” “ mania , ” “ mixed episode , ” or “ bipolar depression , ” cross-referenced with trial characteristic search phrases and generic names of medications . The search was supplemented by manually review ing reference lists from identified publications . Results In 15 studies , aripiprazole , olanzapine , quetiapine , risperidone long-acting injection , lithium , lamotrigine , and divalproex proved effectiveness in terms of NNTs ( ≥10 % advantage over placebo ) for prevention of relapse into any mood episode . Quetiapine , lithium , risperidone long-acting injection , aripiprazole , and olanzapine are effective in manic recurrence prevention .  Lamotrigine , quetiapine , and lithium present significant NNTs for prevention of depressive relapses . Conclusions All of the pharmacological agents assessed were effective in the prevention of any kind of mood episode ; however , different efficacy profiles were found for prevention of manic and /or depressive relapses . The comparison of NNT values of the available agents may represent a useful tool in clinical setting s , in order to facilitate implementation of long-term pharmacological interventions in patients with BD OBJECTIVES To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant ( AD ) treatment by examining bipolar patients with psychosis early in their illness course . METHODS A multi-facility cohort of 123 first-admission in patients , aged 15 - 60 years , with DSM-IV bipolar disorder ( BD ) with psychotic features , was followed for four years , and 76 individuals experienced at least one episode of depression .  Frequency of and risk factors for switches from depression to mania , time to switch , and duration of the subsequent manic episode were examined in relation to AD use ( with anti-manic and /or antipsychotic medications ) . RESULTS The 76 respondents experienced 113 depressive episodes . Those prescribed ADs had more depressive episodes and spent more time depressed than non-users . A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode ( 20 % ) . The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs . None of the risk factors ( age of onset < or=18 years , childhood psychopathology , depressive first episode , substance abuse at index admission , bipolar family history , type of AD used ) was associated with switching . CONCLUSIONS In this sample with severe BD , switching from depression to mania was not associated with AD treatment . Respondents who experienced switching appeared to have a more relentless form of BD . In only a few did ADs appear to be responsible for the switch OBJECTIVE To assess quetiapine effectiveness in bipolar disorder ( BD ) patients in a clinical setting . METHODS We naturalistically administered open quetiapine to out patients assessed with the Systematic Treatment Enhancement Program for BD ( STEP-BD ) Affective Disorders Evaluation , and monitored longitudinally with the STEP-BD Clinical Monitoring Form . RESULTS 96 patients ( 36 BD I , 50 BD II , 9 BD NOS , 1 Schizoaffective Bipolar Type , mean ± SD age 42.3 ± 13.8 years , 66.7 % female ) received quetiapine , combined with an average of 2.5 ( in 66.7 % of patients at least 2 ) other psychotropic medications and 0.9 non-psychotropic medications , started most often during depressive symptoms ( 53.1 % ) or euthymia ( 37.5 % ) . Mean quetiapine duration and final dose were 385 days and 196 mg/day ( 50.0 % of patients took ≤75 mg/day ) . Quetiapine was discontinued in 38.5 % of trials , after on average 307 days , most often ( in 19.8 % ) due to CNS adverse effects ( primarily sedation ) . In 38.5 % of trials quetiapine was continued on average 328 days with no subsequent psychotropic added . In 22.9 % quetiapine was continued on average 613 days , but had subsequent psychotropic added after on average 113 days , most often for depressive symptoms . In 67 trials started at Stanford , quetiapine tended to primarily maintain euthymia and relieve depressive symptoms . In 29 trials started prior to Stanford , continuing quetiapine tended to primarily maintain euthymia and relieve mood elevation symptoms . Aside from sedation  , quetiapine was generally well tolerated . CONCLUSIONS In bipolar disorder out patients  quetiapine had a moderate ( 38.5 % , with 385-day mean duration ) discontinuation rate , and commonly did not require subsequent additional pharmacotherapy , suggesting effectiveness in a clinical setting Few long‐term studies on bipolar disorder ( BD ) have investigated the incidence and risk factors of suicide attempts ( SAs ) specifically related to illness phases . We examined the incidence of SAs during different phases of BD in a long‐term prospect i ve cohort of bipolar I ( BD‐I ) and bipolar II ( BD‐II ) patients , and risk factors specifically for SAs during major depressive episodes ( MDEs ) OBJECTIVE To determine if the repeated occurrence of manic episodes in bipolar I disorder ( BD-I ) patients is associated with reduced cognitive performance , which could in turn imply a worsening in the disorder 's evolution . METHOD Cognitive performance in euthymic patients was assessed using  attention , memory , and executive function tests  on 24 BD-I patients who had experienced only 1 manic episode , on 27 BD-I patients with 2 manic episodes , on 47 BD-I patients with 3 or more manic episodes , and on 66 healthy control subjects . RESULTS In BD-I patients , number of manic episodes was positively associated with poorer performance on neurocognitive tests , an association that was not accounted for by depression , disease chronicity , onset , or medication . Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more . CONCLUSION The number of manic episodes predicted poor cognitive performance , suggesting that the recurrence of mania may have a long-term neuropsychological impact . Prospect i ve follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function BACKGROUND Bipolar depression ( BD ) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness . Pharmacological treatments for BD might further aggravate cognitive impairment , highlighting the need of developing interventions that present cognitive safety . In this study , we evaluated the cognitive effects of H1-coil ( deep ) transcranial magnetic stimulation ( TMS ) in patients with treatment-resistant bipolar depression . METHODS Fourty-three patients were r and omized to receive 20 sessions of active ( 55 trains , 18 Hz , 120 % resting motor threshold intensity ) or sham rTMS within a double-blind , sham-controlled trial . A battery of 20 neuropsychological assessment s , grouped in 6 domains ( attention and processing speed , working memory and executive function , inhibitory control , language , immediate verbal memory , and long-term verbal memory ) was performed at baseline and after 4 and 8 weeks of trial onset . Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression . RESULTS Cognitive improvement was shown for all cognitive domains . It occurred regardless of intervention group and depression improvement . For the language domain , greater improvement was observed in the sham group over time . No correlations between depression ( at baseline or during treatment ) and cognitive improvement were found . LIMITATIONS Absence of healthy control group . CONCLUSION The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients . Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated BACKGROUND Inferior response to lithium treatment  has been reported in bipolar disorder ( BD ) patients with mania or hypomania following episodes of major depression ( DMI ) versus preceding depression ( MDI ) , with intervening euthymic periods . However , additional characteristics of BD course-patterns require further assessment . METHODS We review ed computerized clinical records and life-charts of 855 DSM-IV-TR BD-I or -II patients assessed and followed at mood-disorder centers in Cagliari or Rome to characterize their predominant course-sequences . RESULTS Morbidity over an average of 9.5 cycles in 18 years was characterized for sequencing of illness-episodes and euthymic intervals . Prevalent sequences included : major depression-hypomania ( 15.0 % ) , mania-major depression ( 14.6 % ) , major depression-mania ( 11.6 % ) , and rapid-cycling ( 9.6 % ) . Among subjects grouped by course-sequences ( based on mania , mixed-states , or hypomania and major or minor depression ) , depression-before-[hypo]mania ( DMI ) cases were more likely to be women , diagnosed BD-II , have first-episodes of depressive or anxiety disorder , spend more time ill in depression , and benefit less with long-term mood-stabilizing treatments than with the opposite pattern ( MDI ) . MDI patients were more likely to have substance-abuse and receive long-term mood-stabilizer treatments . Meta- analysis of 5 previous reports plus present findings found inferior treatment-response in DMI vs. MDI cases at a pooled risk-difference of 29 % [ CI : 18 - 40 % ] ( p<0.0001 ) . LIMITATIONS Some data were retrospective and subject to recall bias , and treatment was clinical ( non-r and omized ) . CONCLUSIONS The DMI course was strongly associated with first-episode depression or anxiety , excess depressive morbidity , and inferior treatment response , especially for depression Objectives The treatment of bipolar disorder type I ( BD-I ) with a comorbid cocaine dependence disorder ( CDD ) is a challenge in current psychiatric practice . Drugs with proven efficacy in manic/mixed episodes , such as atypical antipsychotics and mood stabilizers , sometimes do not prevent depressive relapses ; on the other h and , the use of antidepressants during acute depressive episodes may increase the risk of a manic switch . The aim of the present study was to investigate the short-term efficacy of bupropion augmentation in acutely depressed BD-I patients with co-occurring CDD . Methods Twelve depressed BD-I patients , with a comorbid CDD , treated with valproate 1000 to 1500 mg/d and aripiprazole 10 mg/d , were r and omly assigned to receive bupropion 150 mg/d as an open-label add-on therapy ( n = 5 ) or to continue their previous treatment ( n = 7 ) . Results After 4 weeks of observation , patients receiving add-on therapy with bupropion have improved in terms of Hamilton Depression Rating Scale scores and Drug Abuse Screening Test scores , with respect to those of the comparison group , whereas no significant increase of Young Mania Rating Scale scores over time was observed . Conclusions Our preliminary findings suggest that combining bupropion with mood stabilizers and atypical antipsychotics may be a good therapeutic option in short-term treatment of depressed BD-I patients with comorbid CDD Objective : In adults with established bipolar disorder ( BD ) , differential response to  mood stabilizers  has been associated with the clinical profile . Long-term treatment studies of youth with BD are lacking . This paper provides longitudinal observations of response to  mood stabilizers  early in the course of illness in youth with BD . Method : We report on 15 research patients who , as adolescents , met DSM-IV lifetime criteria for a bipolar spectrum disorder and required long-term treatment . These youths derived from families with one parent having BD whose course and long-term treatment response were determined in accordance with research criteria . The patients were offered lithium , and if they failed to respond or refused it , they were treated with either an anticonvulsant or an atypical antipsychotic . Using a vali date d scale , an independent rater retrospectively blindly scored the response to long-term treatment . Results : Those patients who stabilized on  lithium  derived from lithium-responsive families , whereas those who stabilized on an  antipsychotic  derived from lithium-nonresponsive families . The clinical course in the youths stabilized by lithium differed from that in the youths stabilized by an atypical antipsychotic . Conclusions : Our findings suggest that the clinical profile may help in selecting effective stabilizing treatment and that a proportion of youth can be stabilized on monotherapy . This is a small case series with nonr and om treatment assignment , and the findings should be considered tentative Abstract Although a frequent co-occurrence between bipolar disorder ( BD ) and conduct disorder ( CD ) in youth has been frequently reported , data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice , but no comparative studies are available . The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD . Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , ( male/female ratio , 12/10 ; mean ( SD ) age 15.0 ( 1.4 ) years ) were r and omized in 2 treatment groups  ( quetiapine [ n = 12 ] vs risperidone [ n = 10 ] ) , treated with flexible doses , and followed up for 12 weeks . Efficacy measures assessed manic symptoms , aggression , anxiety , depression , global clinical severity , and impairment . Safety measures included body mass index , serum prolactin , extrapyramidal adverse effects , and electrocardiogram . At the end of the study , all patients improved in all efficacy measures . Both treatments showed similar efficacy in reducing manic symptoms and aggression . Quetiapine was more effective in improving anxiety and depressive symptoms . A change in body mass index was found , and in a post hoc analysis , it was significant only in the risperidone group . Prolactin significantly increased only in the risperidone group . In BD type II , CD comorbidity , quetiapine , or risperidone monotherapy may be effective and relatively safe , although the small sample size , the limited duration of the study , and the design ( lack of a blind assessment s and of a placebo group ) make it difficult to draw definitive conclusions BACKGROUND Controversy exists over antidepressant use in rapid-cycling bipolar disorder . AIMS Exploratory analysis of safety and efficacy of fluoxetine v. lithium monotherapy in individuals with rapid- v. non-rapid-cycling bipolar II disorder . METHOD R and omised , double-blind , placebo-controlled comparison of fluoxetine v. lithium monotherapy in patients initially stabilised on fluoxetine monotherapy ( trial registration NCT00044616 ) . RESULTS The proportion of participants with depressive relapse was similar between the rapid- and non-rapid-cycling groups ( P = 0.20 ) . The odds of relapse were similar between groups ( P = 0.36 ) . The hazard of relapse was similar between groups ( hazard ratio 0.87 , 95 % CI 0.40 - 1.91 ) . Change in mania rating scores was similar between groups ( P = 0.86 ) . There was no difference between groups in the rate of syndromal ( P = 0.27 ) or subsyndromal ( P = 0.82 ) hypomania . CONCLUSIONS Depressive relapse and treatment-emergent mood conversion episode rates were similar for lithium and fluoxetine monotherapy and placebo during long-term , relapse-prevention therapy of rapid- and non-rapid-cycling bipolar II disorder OBJECTIVES People in the late stage of bipolar disorder ( BD ) experience elevated relapse rates and poorer quality of life ( QoL ) compared with those in the early stages . Existing psychological interventions also appear less effective in this group . To address this need , we developed a new online mindfulness-based intervention targeting quality of life ( QoL ) in late stage BD . Here , we report on an open pilot trial of ORBIT ( online , recovery-focused , bipolar individual therapy ) . METHODS Inclusion criteria were : self-reported primary diagnosis of BD , six or more episodes of BD , under the care of a medical practitioner , access to the internet , proficient in English , 18 - 65 years of age . Primary outcome was change ( baseline - post-treatment ) on the Brief QoL.BD  ( Michalak and Murray , 2010 ) . Secondary outcomes were depression , anxiety , and stress measured on the DASS scales ( Lovibond and Lovibond , 1993 ) . RESULTS Twenty-six people consented to participate ( Age M=46.6 years , SD=12.9 , and 75 % female ) . Ten participants were lost to follow-up ( 38.5 % attrition ) . Statistically significant improvement in QoL was found for the completers , t(15)=2.88 , 95 % CI:.89 - 5.98 , p=.011 , ( Cohen׳s dz=.72 , partial η(2)=.36 ) , and the intent-to-treat sample t(25)=2.65 , 95 % CI:.47 - 3.76 , ( Cohen׳s dz=.52 ; partial η(2)=.22 ) . A non-significant trend towards improvement was found on the DASS anxiety scale ( p=.06 ) in both completer and intent-to-treat sample s , but change on depression and stress did not approach significance . LIMITATIONS This was an open trial with no comparison group , so measured improvements may not be due to specific elements of the intervention . Structured diagnostic assessment s were not conducted , and interpretation of effectiveness was limited by substantial attrition . CONCLUSION Online delivery of mindfulness-based psychological therapy for late stage BD appears feasible and effective , and ORBIT warrants full development . Modifications suggested by the pilot study include increasing the 3 weeks duration of the intervention , adding caution s about the impact of extended meditations , and addition of coaching support/monitoring to optimise engagement Genome-wide association studies ( GWASs ) have identified several susceptibility loci for bipolar disorder ( BD ) and shown that the genetic architecture of BD can be explained by polygenicity , with numerous variants contributing to BD . In the present GWAS ( Phase I/II ) , which included 2964 BD and 61 887 control subjects from the Japanese population , we detected a novel susceptibility locus at 11q12.2 ( rs28456 , P=6.4 × 10−9 ) , a region known to contain regulatory genes for plasma lipid levels ( FADS1/2/3 ) . A subsequent meta- analysis of Phase I/II and the Psychiatric GWAS Consortium for BD ( PGC-BD ) identified another novel BD gene , NFIX ( Pbest=5.8 × 10−10 ) , and supported three regions previously implicated in BD susceptibility : MAD1L1 ( Pbest=1.9 × 10−9 ) , TRANK1 ( Pbest=2.1 × 10−9 ) and ODZ4 ( Pbest=3.3 × 10−9 ) . Polygenicity of BD within Japanese and trans-European-Japanese population s was assessed with risk profile score analysis . We detected higher scores in BD cases both within ( Phase I/II ) and across population s ( Phase I/II and PGC-BD ) . These were defined by ( 1 ) Phase II as discovery and Phase I as target , or vice versa ( for ‘ within Japanese comparisons ’ , Pbest~10−29 , R2~2 % ) , and ( 2 ) European PGC-BD as discovery and Japanese BD ( Phase I/II ) as target ( for ‘ trans-European-Japanese comparison , ’ Pbest~10−13 , R2~0.27 % ) . This ‘ trans population ’ effect was supported by estimation of the genetic correlation using the effect size based on each population ( liability estimates~0.7 ) . These results indicate that ( 1 ) two novel and three previously implicated loci are significantly associated with BD and that ( 2 ) BD ‘ risk ’ effect are shared between Japanese and European population 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 Objective : Psychosocial research in bipolar disorder ( BD ) has not yet assessed the relative benefits of a short course of psychoeducation ( PE ) , compared with a longer course of cognitive-behavioural therapy ( CBT ) containing psychoeducational principles . This pilot study evaluated the efficacy and added benefit of adding a course of CBT to a st and ard course of brief PE , as maintenance therapy for BD . Method : Seventy-nine consenting adult men and women with BD on stable medication regimens , who were in full or partial remission from an index episode ( BD I = 52 ; BD II = 27 ) , were r and omized to receive either 7 sessions of individual PE , or 7 sessions of PE followed by 13 additional individual sessions of CBT .  Weekly mood and medication adherence was rated using the National Institute of Mental Health 's Life Chart Method , while psychosocial functioning and mental health use were assessed monthly . Results : Forty-six participants completed the entire study . Participants who received CBT in addition to PE experienced 50 % fewer days of depressed mood over the course of one year . Participants who received PE alone had more antidepressant increases compared with those who received CBT . There were no group differences in hospitalization rates , medication adherence , psychosocial functioning , or mental health use . Conclusions : Pilot data from this real-world study suggest that even after medication treatment has been optimized , a longer course of adjunctive CBT may offer some additional benefits over a shorter course of PE alone for the maintenance treatment of BD . Larger r and omized controlled trials with equal treatment lengths are indicated . Objectif : La recherche psychosociale dans le trouble bipolaire ( TB ) n'a pas encore évalué les avantages relatifs d'un traitement abrégé de psychoéducation ( PE ) , comparé à un traitement plus long de thérapie cognitivo-comportementale ( TCC ) contenant des principes psychoéducationnels . Cette étude pilote a évalué l'efficacité et l'avantage supplémentaire d'ajouter un traitement de TCC à un traitement st and ard de PE abrégé , comme traitement d'entretien du TB . Méthode : Soixante dix-neuf adultes , hommes et femmes , souffrant de TB et prenant des régimes de médicaments stables , qui étaient en rémission totale ou partielle d'un épisode indice ( TB I = 52 ; TB II = 27 ) , ont été r and omisés pour recevoir soit 6 séances de PE individuelle , soit 6 séances de PE suivies de 14 séances individuelles additionnelles de TCC . L'humeur et l'observance de la médication étaient cotées une fois la semaine à l'aide de la Life Chart Method du National Institute of Mental Health , t and is que le fonctionnement psychosocial et l'usage des services de santé mentale étaient évalués une fois par mois . Résultats : Quarante-six participants ont terminé l'étude au complet . Les participants qui ont reçu la TCC en plus de la PE ont eu 50 % moins de journées d'humeur déprimée sur un an . Les participants qui ont reçu la PE seulement avaient plus d'augmentations d'antidépresseurs que ceux ayant reçu la TCC . Il n'y avait pas de différences entre les groupes en ce qui concerne les taux d'hospitalisation , l'observance des médicaments , le fonctionnement psychosocial ou l'usage des services de santé mentale . Conclusions : Les données pilotes de cette étude de monde réel suggèrent que même après que la médication est optimisée , un traitement plus long de TCC adjointe peut offrir certains avantages additionnels à un traitement abrégé de PE pour le traitement d'entretien du TB . Des essais r and omisés contrôlés plus vastes avec des traitements d'égale longueur sont indiqués For 30 years , bright light therapy ( BLT ) has been considered as an effective , well-tolerated treatment for seasonal affective disorder ( SAD ) . Because of low response rates , new treatment strategies are needed for bipolar depression ( BD ) , which resembles SAD in certain respects . Few placebo-controlled studies of BLT efficacy have been carried out for BD . Accordingly , this study evaluates the efficacy and safety of BLT as an add-on treatment for BD . Thirty-two BD out patients were r and omly assigned to BLT ( 10000lx ) or dim light ( DL , < 500lx ) . During a two-week period , light was administered each morning for 30min . The Hamilton Rating Scale for Depression and the Montgomery-Ǻsberg Depression Rating Scale assessed clinical outcome , and the UKU Side Effects Rating Scale evaluated side effects . No significant difference was observed in baseline depression scores in the  two groups . Response rates for BLT and DL were 81 % and 19 % , and remission rates were 44 % and 12.5 % , respectively . Analyses showed statistically significant reductions in depression scores for the BLT group compared with the DL group on all scales . Side effects were similar in both groups , with headache as the most common side effect . The results suggest that BLT is an effective and safe add-on treatment for BD OBJECTIVE The aim of this study was to evaluate the safety and efficacy of extended release carbamazepine ( CBZ-ER ) monotherapy in the treatment of pediatric bipolar disorder ( BD ) . METHOD This was an 8-week , open-label , prospect i ve trial of CBZ-ER monotherapy ( 788 + /- 252 mg/day ) to assess the effectiveness and tolerability of this compound in treating pediatric bipolar spectrum disorders . Assessment s included the Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions-Improvement scale , Children 's Depression Rating Scale , and Brief Psychiatric Rating Scale . Adverse events were assessed through spontaneous self-reports , vital signs weight monitoring , and laboratory analysis . RESULTS Of the 27 participating children with BD , 16 ( 59.% ) completed the study .  CBZ-ER treatment was associated with statistically significant , but modest , levels of improvement in mean YMRS scores ( -10.1 + /- 10.2 , p < 0.001 ) with end-point mean YMRS score ( 21.8 + /- 12.2 ) suggesting a lack of complete resolution of mania . CBZ-ER treatment also result ed in significant improvement in the severity of depressive , attention-deficit/hyperactivity disorder , and psychotic symptoms . With the exception of 2 participants who discontinued due to skin rash , CBZ-ER was well tolerated with marginal increase in body weight ( 0.8 + /- 2.5 kg , p = 0.04 ) and was not associated with any abnormal changes in laboratory parameters . CONCLUSIONS Open-label CBZ-ER treatment was beneficial for the treatment of BD in children . Future controlled trials are warranted OBJECTIVE Clinicians have few evidence -based options for the management of treatment-resistant bipolar depression .  This study represents the first r and omized trial of competing options for treatment-resistant bipolar depression and assesses the effectiveness and safety of antidepressant augmentation with lamotrigine , inositol , and risperidone . METHOD Participants ( N=66 ) were patients with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) . All patients were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant . Patients were r and omly assigned to open-label adjunctive treatment with lamotrigine , inositol , or risperidone for up to 16 weeks . The primary outcome measure was the rate of recovery , defined as no more than two symptoms meeting DSM-IV threshold criteria for a mood episode and no significant symptoms present for 8 weeks . RESULTS No significant between-group differences were seen when any pair of treatments were compared on the primary outcome measure . However , the recovery rate with lamotrigine was 23.8 % , whereas the recovery rates with inositol and risperidone were 17.4 % and 4.6 % , respectively . Patients receiving lamotrigine had lower depression ratings and Clinical Global Impression severity scores as well as greater Global Assessment of Functioning scores compared with those receiving inositol and risperidone . CONCLUSIONS No differences were found in primary pairwise comparison analyses of open-label augmentation with lamotrigine , inositol , or risperidone . Post hoc secondary analyses suggest that lamotrigine may be superior to inositol and risperidone in improving treatment-resistant bipolar depression BACKGROUND Antidepressant-induced mania ( AIM ) has been described in bipolar disorder ( BD ) and has been associated with the short-allele of the serotonin transporter gene ( 5-HTT ) . We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD . METHODS Fifty-two children and adolescents ( 30 with BD and 22 with subthreshold manic symptoms , 15.1 + /- 3.4 years old ) , all with a parent with BD , were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment .  The 47 subjects with serotonin reuptake inhibitor ( SSRI ) exposure  were genotyped for the 5-HTT polymorphism . RESULTS Fifty percent of subjects were AIM + and 25.5 % had new onset of suicidal ideation . The AIM + and AIM - groups did not differ significantly in relation to allele ( p = .36 ) or genotype ( p = .53 ) frequencies of the 5-HTT polymorphism . The AIM + subjects were more likely to have more comorbidities ( 3.2 vs. 2.4 ; p = .02 ) and be BD type I ( p = .04 ) than AIM - subjects . CONCLUSIONS Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs . In this preliminary study , we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM 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
Antidepressants were superior to placebo in reducing new depressive episodes in bipolar disorders without increasing risk of new manic/hypomanic episodes either used as monotherapy or in combination with MS .
Subgroup analyses revealed that greater benefit and lower risk may be achieved in BD II than in BD I. However , compared with MS monotherapy , AD monotherapy significantly increased the risk of affective switch with no improvement in prophylaxis of new depressive episodes .
CONCLUSIONS Reduced new depressive episodes may be achieved by long-term AD treatment with no significantly increased risk of new manic/hypomanic episodes in BD , particularly in BD II .
The elevated risk of affective switch  of AD monotherapy compared with MS monotherapy may be contributed to the protective effect of MS in diminishing manic/hypomanic episodes .
OBJECTIVE Efficacy and safety of long-term use of antidepressants ( AD ) in bipolar disorder ( BD ) patients remains highly controversial .
Here we performed a meta- analysis of r and omized controlled trials ( RCTs ) exploring the efficacy and safety of long-term AD use in BD patients .