Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Bupropion as an Add-on Therapy in Depressed Bipolar Disorder Type I Patients With Comorbid Cocaine Dependence First do no harm: promoting an evidence-based approach to atypical antipsychotic use in children and adolescents. A Pilot, 15-month, randomised effectiveness trial of Risperidone long-acting injection (RLAI) versus oral atypical antipsychotic agents (AAP) in persons with bipolar disorder. Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo-controlled pilot study. Course sequences in bipolar disorder: depressions preceding or following manias or hypomanias. Does psychomotor agitation in major depressive episodes indicate bipolarity? A Consecutive Series of Treated Affected Offspring of Parents with Bipolar Disorder: Is Response Associated with the Clinical Profile? Recognizing mania in children and adolescents-age does not matter, but decreased need for sleep does. Antidepressant-associated switches from depression to mania in severe bipolar disorder. Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM). An open label follow-up study on amisulpride in the add-on treatment of bipolar I patients Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder Peripheral brain-derived neurotrophic factor changes along treatment with extended release quetiapine during acute mood episodes: an open-label trial in drug-free patients with bipolar disorder. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone. A preliminary functional magnetic resonance imaging study of prefrontal-amygdalar activation changes in adolescents with bipolar depression treated with lamotrigine. Focus on aripiprazole: a review of its use in child and adolescent psychiatry. Risk factors for antidepressant-related switch to mania. Interpersonal and social rhythm therapy for adolescents with bipolar disorder: treatment development and results from an open trial Family-focused treatment for adolescents with bipolar disorder. Olanzapine/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: a post hoc analysis. A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. 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 Early psychosocial intervention for youth at risk for bipolar I or II disorder: a one-year treatment development trial. Efficacy of quetiapine and risperidone against depressive symptoms in outpatients with psychosis. Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study. Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial. Controlled trial of safety and efficacy of bright light therapy vs. negative air ions in patients with bipolar depression Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder Long-term effectiveness of quetiapine in bipolar disorder in a clinical setting. Anger attacks in bipolar depression: predictors and response to citalopram added to mood stabilizers. Pharmacotherapy and family-focused treatment for adolescents with bipolar I and II disorders: a 2-year randomized trial. A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder. Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES). Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial. Reduced mania and depression in juvenile bipolar disorder associated with long-chain ω-3 polyunsaturated fatty acid supplementation A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder Divalproex monotherapy in the treatment of bipolar offspring with mood and behavioral disorders and at least mild affective symptoms. Augmenting psychoeducation with a mobile intervention for bipolar disorder: a randomized controlled trial. Aripiprazole augmentation in treatment-resistant bipolar depression: Early response and development of akathisia Quetiapine for the continuation treatment of bipolar depression: naturalistic prospective case series from the Stanley Bipolar Treatment Network Subsyndromal symptoms assessed in longitudinal, prospective follow-up of a cohort of patients with bipolar disorder. Quetiapine alone and added to a mood stabilizer for serious mood disorders. Implicit motor learning in bipolar disorder. Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life.
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 Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines . The authors looked for the features associated with risk of recurrence . METHOD The authors examined prospect i ve data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) study for up to 24 months . For those who were symptomatic at study entry but subsequently achieved recovery , time to recurrence of mania , hypomania , mixed state , or a depressive episode was examined with Cox regression . RESULTS Of 1,469 participants symptomatic at study entry , 858 ( 58.4 % ) subsequently achieved recovery . During up to 2 years of follow-up , 416 ( 48.5 % ) of these individuals experienced recurrences , with more than twice as many developing depressive episodes ( 298 , 34.7 % ) as those who developed manic , hypomanic , or mixed episodes ( 118 , 13.8 % ) . The time until 25 % of the individuals experienced a depressive episode was 21.4 weeks and until 25 % experienced a manic/hypomanic/mixed episode was 85.0 weeks . Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence . Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic , hypomanic , or mixed episode recurrence . CONCLUSIONS Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery . Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence OBJECTIVE Bipolar disorder is highly comorbid with substance use disorders , and this comorbidity may be associated with a more severe course of illness , but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined . The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder . METHOD Subjects ( N=3,750 ) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) were followed prospect ively for up to 2 years . Prospect ively observed depressive episodes were identified for this analysis . Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic , hypomanic , or mixed episode . RESULTS During follow up , 2,154 subjects developed a new-onset major depressive episode ; of these , 457 subjects switched to a manic , hypomanic , or mixed episode prior to recovery . Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity . However , those with current or past substance use disorder were more likely to experience switch from depression directly to a manic , hypomanic , or mixed state . CONCLUSIONS Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic , mixed , or hypomanic states . The mechanism conferring this increased risk merits further study 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 OBJECTIVES To review the evidence for efficacy and metabolic effects of atypical antipsychotics ( AAPs ) , and to propose a metabolic monitoring protocol for AAP use in children and adolescents . METHODS A PubMed search was performed to obtain all studies related to efficacy , metabolic side-effects , and monitoring in those less than 18 years of age . RESULTS There are no approved indications for AAP use in children and adolescents in Canada . Based on US Food and Drug Administration approvals and a review of r and omized controlled trials , we identified 7 indications for AAP use that target specific symptoms in youth including schizophrenia , bipolar I disorder , autism , pervasive developmental disorder , disruptive behaviour disorders ( including conduct disorder and ADHD ) , developmental disabilities and Tourette Syndrome . A wide range of metabolic effects including weight gain , increased waist circumference , dysglycemia , dyslipidemia , hypertension , elevated hepatic transaminases and prolactin levels have been reported . We have developed a proposal for metabolic monitoring that includes anthropometric measurements and laboratory testing at baseline and appropriate intervals thereafter . CONCLUSION There is an urgent need for national clinical practice guidelines that provide , not only appropriate treatment algorithms for AAP-use based on evidence , but also address metabolic monitoring and subsequent management of complications in this vulnerable population UNLABELLED Chengappa KNR , Turkin SR , Schlicht PJ , Murphy SL , Brar JS , Fagiolini A , Houck PR , Garbutt RG , Fredrick N. A Pilot , 15-month , r and omised effectiveness trial of Risperidone long acting injection ( RLAI ) versus oral atypical antipsychotic agents ( AAP ) in persons with bipolar disorder . OBJECTIVE Long-acting injectible antipsychotic agents are rarely considered in the treatment of bipolar patients [ bipolar disorder ( BPD ) ] . We posited that BPD patients receiving risperidone long-acting injections  [ Risperidone long-acting injections ( RLAIs ) ] would experience fewer negative clinical events than those receiving oral atypical antipsychotic agents ( AAP ) . METHODS Adult BPD patients in a hypomanic , manic or mixed episode were r and omised to either oral risperdone followed by RLAI ( n = 23 ) or an AAP ( n = 25 ) for 15 months . Any mood stabilizers were continued . An independent clinician board declared any clinical events that occurred but the treatment assignment was concealed . RESULTS Nine of the 48 patients who participated in this study did not improve , leaving 39 patients in 1-year extension . RLAI patients received the following bi-weekly dosages : 25 mg ( n = 9 ) , 37.5 mg ( n = 8) , and 50 mg ( n = 6 ) . The AAP group included aripiprazole ( n = 11 , 15 - 30 mg/day ) , quetiapine ( n = 8 , 300 - 700 mg/day ) , olanzapine ( n = 5 , 15 - 25 mg/day ) , and ziprasidone , ( n = 1 , 160 mg/day ) . In total , 47 clinical events were declared . The RLAI-treated group experienced significantly fewer clinical events ( mean : 0.86 ± 0.73 ) compared with the AAP group ( 1.61 ± 1.29 ) , t = 2.29 , d.f . = 37 , p = 0.028 ( 95 % CI = 0.087 - 1.421 ) . Of all , 50 % of the AAP subjects gained ≥ 7 % of their baseline body weight as did 38 % of the RLAI-treated patients . CONCLUSIONS RLAI-treated patients experienced significantly fewer negative clinical events . Further exploration should focus on which subtypes of BPD patients might benefit from RLAI treatment . Weight gain in BPD subjects requires clinical attention . Limitations include an open design , small sample size and the inability to conclude on whether this strategy is useful for depressive episodes OBJECTIVE The use of atypical antipsychotics ( AAPs ) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated , and aripiprazole showed positive effects in the treatment of unipolar depression . However , no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet . METHODS In this prospect i ve , double-blind ,  placebo-controlled  , r and omized trial , 23 in patients with bipolar depression according to DSM-IV criteria were included . Before r and omization , patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week . After inclusion , all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks . The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale ( HDRS ) within 6 weeks . RESULTS After 6 weeks of treatment , the HDRS score decreased in both groups . There was no significant difference between both the groups at any point of time with respect to the HDRS . CONCLUSIONS Derived from this small pilot study , adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression . However , this lack of additional benefit seems to stem from the already good effectiveness of the control group , namely the treatment with citalopram 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 Abstract Background Kraepelin ’s partial interpretation of agitated depression  as a mixed state of “ manic-depressive insanity ” ( including the current concept of bipolar disorder ) has recently been the focus of much research . This paper tested whether , how , and to what extent both psychomotor symptoms , agitation and retardation in depression are related to bipolarity and anxiety . Method The prospect i ve Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults ( N = 591 ) ( aged 20 at first interview ) by six interviews over 20 years ( 1979–1999 ) .  Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 ( five interviews ) on the basis of the observed and reported behaviour within the interview section on depression . Psychiatric diagnoses were strictly operationalised and , in the case of bipolar-II disorder , were broader than proposed by DSM-IV-TR and ICD-10 . As indicators of bipolarity , the association with bipolar disorder , a family history of mania/hypomania/cyclothymia , together with hypomanic and cyclothymic temperament as assessed by the general  behavior inventory  ( GBI ) [ 15 ] , and mood lability ( an element of cyclothymic temperament ) were used . Results Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety . Longitudinally , agitation and retardation were significantly associated with each other ( OR = 1.8 , 95 % CI = 1.0–3.2 ) , and this combined group of major depressives showed stronger associations with bipolarity , with both hypomanic/cyclothymic and depressive temperamental traits , and with anxiety . Among agitated , non-retarded depressives , unipolar mood disorder was even twice as common as bipolar mood disorder . Conclusion Combined agitated and retarded major depressive states are more often bipolar than unipolar , but , in general , agitated depression ( with or without retardation ) is not more frequently bipolar than retarded depression ( with or without agitation ) , and pure agitated depression is even much less frequently bipolar than unipolar . The findings do not support the hypothesis that agitated depressive syndromes are mixed states . Limitations The results are limited to a population up to the age of 40 ; bipolar-I disorders could not be analysed ( small N ) 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 BACKGROUND The diagnosis of pediatric bipolar disorders is a controversial topic . If this is mainly due to a bias against a diagnosis in younger children , then just changing the information about the age of a patient should influence the likelihood of a diagnosis despite otherwise identical symptoms . Therefore , we design ed a study to test if the age of a patient will influence diagnostic decisions . We further attempted to replicate an earlier result with regard to " decreased need for sleep " as a salient symptom for mania . METHODS We r and omly sent 1 of 4 case vignettes describing a person with current mania to child/adolescents psychiatrists in Germany . This vignette was systematic ally varied with respect to age of the patient ( 6 vs 16 years ) and the presence/absence of decreased need for sleep but always included sufficient criteria to diagnose a mania . RESULTS One hundred sixteen responded and , overall , 63.8 % of the respondents diagnosed a bipolar disorder in the person described in the vignette . Although age did not affect the likelihood of a bipolar diagnosis , the presence of decreased need for sleep did increase its likelihood . Furthermore , the number of core symptoms identified by the clinicians was closely linked to the likelihood of assigning a bipolar diagnosis . CONCLUSION Certain symptoms such as the decreased need for sleep , and also elated mood and gr and iosity , seem to be salient for some clinicians and influence their diagnoses . Biological age of the patient , however , does not seem to cause a systematic bias against a diagnosis of bipolar disorder in children 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 BACKGROUND The risk of switching from mania to depression in bipolar disorder has been poorly studied . Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in " real world " patients . METHOD EMBLEM ( European Mania in Bipolar Longitudinal Evaluation of Medication ) is a 2-year , prospect i ve , observational study of patients with a manic/mixed episode . Symptom severity measures included Clinical Global Impression-Bipolar Disorder scale ( CGI-BP ) , Young Mania Rating Scale ( YMRS ) and 5-item Hamilton Depression Rating Scale . Switching was defined using CGI-BP mania and depression such that patients changed from manic and not depressed to depressed but not manic over two consecutive observations within the first 12 weeks of follow-up . Cox proportional hazards models identified baseline variables independently associated with switch to depression . RESULTS Of 2390 patients who participated in the maintenance phase ( i.e. up to 24 months ) , 120 ( 5.0 % ) switched to depression within the first 12 weeks . Factors associated with greater switching to depression include previous depressive episodes , substance abuse , greater CGI-BP overall severity and benzodiazepine use . Factors associated with lower switching rates were greater CGI-BP depression , lower YMRS severity and atypical antipsychotic use . LIMITATIONS The definition of switching biased against patients with mixed episodes being likely to switch . CONCLUSIONS Strictly defined , switch to depression from mania occurs in a small proportion of bipolar patients . Clinical history , illness severity , co-morbidities and treatment patterns are associated with switching to depression . Atypical antipsychotics may protect against switch to depression Background Atypical antipsychotics are widely used in the treatment of bipolar disorders .  Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia , major depressive disorder and , more recently , acute mania . At the moment , however , no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders . The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with st and ard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing st and ard therapies .  Methods The study enrolled fourteen bipolar I out patients , not responding to ongoing st and ard therapy .  Three patients discontinued treatment but 11 were followed-up for 11.7 ± 8.2 months before ( range 3–24 months ) and 5.2 ± 2.7 months after the introduction of amisulpride ( range 3–9 months ) . Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version ( CGI-BP ) score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization . Results A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride . The relative risk of relapse in the absence of amisulpride therapy was 3.1 ( χ2 = 4.2 , P < 0.05 ) . Similarly , the rates of manic/mixed and depressive relapse were decreased but only manic episodes reached statistical significance ( RR = 5.3 , χ2 = 5.2 , P < 0.02 ) . Discussion and conclusion This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses . Large , r and omized , double-blind , placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to st and ard therapies for bipolar disorder 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 Molecules that are involved in neuronal intercommunication and adaptability of neural networks , such as brain-derived neurotrophic factor ( BDNF ) , are targets of pathophysiological investigation in bipolar disorder ( BD ) . Quetiapine is an attested treatment in this disorder , used in acute mood episodes . The aim of this study was to report prospect i ve changes in serum BDNF levels in drug-free patients in acute mood episodes of BD who received treatment with extended-release quetiapine  along a 16 week follow-up . Assessment s were performed at baseline and weeks 2 , 4 , 8 and 16 with the Young Mania Rating Scale , the Hamilton Depression Rating Scale and the Clinical Global Impression severity scale . In these visits , serum BDNF levels were measured . Mixed effect models were used to investigate longitudinal changes . Twenty-five patients were included for this analysis , seventeen in a current depressive episode and eight in a manic/mixed episode . A significant improvement from baseline to endpoint was displayed . In the mixed model , significant main effects for episode and time appeared , and a time versus episode interaction showing increasing BDNF levels with time in those with a depressive episode , but a decrease in BDNF levels with time in those with a manic/mixed episode . BDNF may be a biomarker with differential response according to the polarity of mood episodes 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 Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder . Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse , compared with lithium or valproate alone . METHOD Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium ( 0.6 - 1.2 mmol/l ) or valproate ( 50 - 125 microg/ml )  received lithium or valproate plus either olanzapine 5 - 20 mg/day ( combination therapy ) or placebo ( monotherapy ) , and were followed in a double-masked trial for 18 months . RESULTS The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse ( median time to relapse : combination therapy 94 days , monotherapy 40.5 days ; P=0.742 ) , but was significant for symptomatic relapse ( combination therapy 163 days , monotherapy 42 days ; P=0.023 ) . CONCLUSIONS Patients taking olanzapine  added to lithium or valproate experienced sustained symptomatic remission , but not syndromic remission , for longer than those receiving lithium or valproate monotherapy OBJECTIVES Hypotheses regarding mood dysregulation in bipolar disorder ( BD ) have centered on limbic overactivity with relative prefrontal underactivity during mood episodes . Therefore , we hypothesized that adolescents with bipolar depression successfully treated with lamotrigine would show decreases in amygdalar activation , and increases in prefrontal activation . METHODS Eight adolescents with BD underwent  functional magnetic resonance imaging ( fMRI ) at baseline and after eight weeks of lamotrigine treatment .  Blocks of negatively and neutrally valenced emotional pictures were presented during scanning , and subjects were asked to rate how each picture made them feel . Activation in bilateral amygdalae and dorsolateral prefrontal cortices ( DLPFC ) for negative minus neutral pictures was correlated with Children 's Depression Rating Scale ( CDRS ) scores . RESULTS Mean ( SD ) CDRS scores decreased significantly , from 53.0 ( 10.6 ) at baseline to 26.3 ( 5.3 ) at Week 8 . This clinical improvement was correlated with decreased right amygdalar activation ( r = 0.91 , p = 0.002 ) . At Week 8 , but not baseline , CDRS score was positively correlated with bilateral amygdalar activation ( r = 0.85 , p = 0.007 ) . DLPFC activation was not correlated with change in CDRS score . CONCLUSIONS These preliminary results indicate that adolescents with BD treated with lamotrigine demonstrated less amygdalar activation when viewing negative stimuli as depressive symptoms improved . Larger controlled studies are needed to confirm these findings OBJECTIVE To review published literature regarding aripiprazole in child and adolescent psychiatry . METHOD A literature review was conducted using the medline search term : ' aripiprazole ' with limits : Human trials , English language , All Child ( aged 0 - 18 years ) . Additional articles were identified from reference information and poster presentation data . RESULTS Aripiprazole is an atypical antipsychotic which was recently approved for use in Canada , but has been available for several years in the United States . Pharmacologically , aripiprazole is a partial agonist at D(2 ) and 5-HT(1A ) receptors and an antagonist at 5-HT(2A ) receptors . R and omized controlled trial data is available showing efficacy for aripiprazole in the treatment of children and adolescents with schizophrenia , bipolar disorder and behavioural problems associated with autism . Open-label evidence is also available for use of aripiprazole in other disorders such as tic disorders , aggression and disruptive behavior disorders . Unlike some other available atypical antipsychotics , there does not appear to be any effect on QTc interval on the electrocardiogram . Adverse effects including extrapyramidal symptoms ( EPS ) , akathisia , sedation , headache , nausea were significant in clinical trials in children and adolescents . The possibility of aripiprazole causing tardive dyskinesia can not be excluded . In this population , aripiprazole appears to have minimal impact on the metabolic profile compared to most other atypical antipsychotics , with minimal changes in weight or body mass index , no significant changes in glucose or lipid metabolism , and a decrease in serum prolactin . CONCLUSION Aripiprazole may represent an important alternative for some children and adolescents who have experienced poor efficacy or significant metabolic adverse effects with their current antipsychotic treatment regimen OBJECTIVE Treatment of bipolar depression with antidepressants is strongly debated on the basis of the method ologically poor and insufficient data supporting their use and the widely held belief that antidepressants can induce new episodes of abnormal mood elevation or accelerate the rate of cycling . The present study aim ed at identifying clinical risk factors for switch into hypomania , mania , or mixed states , within 8 weeks after introduction of an antidepressant or after increasing its dosage , in a prospect i ve , longitudinal design . METHOD 221 consecutive DSM-IV-TR depressed bipolar I and II disorder patients were treated with antidepressants , which were added to previously prescribed mood stabilizers and /or atypical antipsychotics . No patient was on antidepressant monotherapy .  The patients were enrolled from October 2005 through January 2010 . The primary outcome was the assessment of switch to mania or hypomania within 8 weeks after the introduction or dose increase of an antidepressant  . Both groups were compared with analysis of variance and χ² procedures . RESULTS Treatment-emergent affective switch was detected in 54 patients ( 24.4 % ) ( switch group ) while 167 patients ( 75.6 % ) ( nonswitch group ) did not experience a treatment-related switch . The main clinical differences significantly associated with the occurrence of an antidepressant-related switch , after performing logistic regression analysis , were higher rate of previous switches ( P < .001 ) in the switch versus the nonswitch group , lower rate of responses to antidepressants ( P < .001 ) in the switch versus the nonswitch group , and earlier age at onset ( P = .026 ) in the switch versus the nonswitch group . DISCUSSION Bipolar patients with an earlier age at onset and an illness course characterized by lower rate of response to antidepressants and higher rate of switches into mania or hypomania were found to be the ones with higher switch risk . Nevertheless , a greater number of previous antidepressant exposures was not associated with the occurrence of an antidepressant-associated switch . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01503489 Background : In adolescents and adults , bipolar disorder ( BD ) is associated with significant morbidity , mortality , and impairment in psychosocial and occupational functioning . IPSRT is an empirically supported adjunctive psychotherapy for adults with bipolar disorder , which has been shown to help delay relapse , speed recovery from a bipolar depressive episode , and increase occupational and psychosocial functioning in adults with BD . This study is design ed to describe the adolescent‐specific developmental adaptations made to IPSRT ( i.e. , IPSRT‐A ) and to report the results from an open trial of IPSRT‐A with 12 adolescents with a bipolar spectrum disorder . Method : Interpersonal and Social Rhythm Therapy was adapted to be developmentally relevant to adolescents with bipolar disorder . Twelve adolescents ( mean age 16.5±1.3 years ) diagnosed with a bipolar spectrum disorder participated in 16–18 sessions of adjunctive IPSRT‐A over 20 weeks . Manic , depressive , and general symptoms and global functioning were measured at baseline , monthly during treatment , and at post‐treatment . Adolescent satisfaction with treatment was also measured . Results : Feasibility and acceptability  of IPSRT‐A were high ; 11/12 participants completed treatment , 97 % of sessions were attended , and adolescent‐rated satisfaction scores were high . IPSRT‐A participants experienced significant decreases in manic , depressive , and general psychiatric symptoms over the 20 weeks of treatment . Participants ' global functioning increased significantly as well . Effect sizes ranged from medium‐large to large . Conclusions : IPSRT‐A appears to be a promising adjunctive treatment for adolescents with bipolar disorder . A current r and omized controlled trial is underway to examine effects of adjunctive IPSRT‐A  on psychiatric symptoms and psychosocial functioning . Depression and Anxiety , 2010 . © 2010 Wiley‐Liss , BACKGROUND Research has begun to eluci date the optimal pharmacological treatments for pediatric-onset bipolar patients , but few studies have examined the role of psychosocial interventions as adjuncts to pharmacotherapy in maintenance treatment . This article describes an adjunctive family-focused psychoeducational treatment for bipolar adolescents ( FFT-A ) . The adult version of FFT has been shown to be effective in forestalling relapses in two r and omized clinical trials involving bipolar adults . METHODS FFT-A is administered to adolescents who have had an exacerbation of manic , depressed , or mixed symptoms within the last 3 months . It is given in 21 outpatient sessions of psychoeducation , communication enhancement training , and problem solving skills training . We describe modifications to the adult FFT model to address the developmental issues and unique clinical presentations of pediatric-onset patients . RESULTS An open treatment trial involving 20 bipolar adolescents ( 11 boys , 9 girls ; mean age 14.8+/-1.6 ) found that the combination of FFT-A and mood stabilizing medications was associated with improvements in depression symptoms , mania symptoms , and behavior problems over 1 year . LIMITATIONS These early results are based on a small-scale open trial . CONCLUSIONS Results from an ongoing r and omized controlled trial will clarify whether combining FFT-A with pharmacotherapy improves the 2-year course of adolescent bipolar disorder . If the results are positive , then a structured manual-based psychosocial approach will be available for clinicians who treat adolescent bipolar patients in the community OBJECTIVE Mixed depression ( ie , co-occurrence of syndromal depression and subsyndromal mania/hypomania ) is a common variant of bipolar depression . However , its treatment is much understudied . The aim of the study was to assess the efficacy of the antipsychotic and mood-stabilizing agent olanzapine and the efficacy of the combination of an antidepressant ( fluoxetine ) and olanzapine ( olanzapine/fluoxetine combination ; OFC ) for the treatment of bipolar I mixed depression . METHOD We carried out a post hoc analysis of an 8-week , double-blind trial of adult bipolar I depression treated with placebo ( n = 355 ) , olanzapine ( 5 - 20 mg/d ; n = 351 ) , or OFC ( olanzapine/fluoxetine doses : 6/25 , 6/50 , 12/50 mg/d ; n = 82 ) . Study ing mixed depression was not a previous goal of the double-blind trial . Subjects in the trial were diagnosed according to DSM-IV and were r and omly assigned to treatment during the period June 2000 to December 2001 . Mixed depression was defined as the co-occurrence of a major depressive episode and > or = 2 manic/hypomanic symptoms ( ie , > or = 2 Young Mania Rating Scale [ YMRS ] items scoring > or = 2 ) . Response was defined as a > or = 50 % reduction in Montgomery-Asberg Depression Rating Scale score and < 2 concurrent manic/hypomanic symptoms . Switching to mania/hypomania was defined as a YMRS score > or = 15 . RESULTS Frequency of mixed depression was 45.1 % in the OFC arm , 49.3 % in the olanzapine arm , and 46.8 % in the placebo arm ( P = .705 ) . The most frequent manic/ hypomanic symptoms of mixed depression were irritability , reduced need for sleep , talkativeness , and racing thoughts . Response rates in patients with nonmixed depression versus patients with mixed depression were the following : in the OFC arm , 48.9 % versus 43.2 % ( OR = 1.24 ; 95 % CI , 0.51 - 2.98 ) ; in the olanzapine arm , 39.9 % versus 26.6 % ( OR = 1.84 ; 95 % CI , 1.17 - 2.90 ) ; in the placebo arm , 27.5 % versus 16.3 % ( OR = 1.94 ; 95 % CI , 1.15 - 3.28 ) . Response rates in the sample s of patients with mixed depression were the following : OFC versus olanzapine , OR = 2.00 ( 95 % CI , 0.96 - 4.19 ) ; OFC versus placebo , OR = 3.91 ( 95 % CI , 1.80 - 8.49 ) ; olanzapine versus placebo , OR = 1.95 ( 95 % CI , 1.14 - 3.34 ) . It was found that no baseline manic/hypomanic symptom of mixed depression predicted treatment response . A higher number of baseline concurrent manic/hypomanic symptoms predicted a lower response rate in the olanzapine and placebo arms , but not in the OFC arm . The rates of switching were the following : in the OFC arm , 8.5 % ; in the olanzapine arm , 6.8 % ; and in the placebo arm , 7.9 % ( P = .808 ) . The rates of dropouts in patients with mixed depression versus patients with nonmixed depression were not significantly different within any of the treatment arms . The rates of dropouts in the sample s of patients with mixed depression were the following : in the OFC arm , 29.7 % ; in the olanzapine arm , 53.8 % ; and in the placebo arm , 59.6 % ( olanzapine vs OFC : OR = 2.66 ; 95 % CI , 1.23 - 5.75 ; placebo vs OFC : OR = 3.48 ; 95 % CI , 1.61 - 7.54 ; placebo vs olanzapine : OR = 1.30 ; 95 % CI , 0.84 - 2.01 ) . CONCLUSION Olanzapine/fluoxetine combination may be an effective treatment for bipolar I mixed depression . Statistically , the efficacy of OFC was not significantly different from that of olanzapine , but inspection of the 95 % CI showed a trend in favor of a possible superiority of OFC . Supporting the study findings are the similar efficacy of OFC in bipolar mixed depression independent of the number of concurrent manic/hypomanic symptoms , a lower dropout rate , and a similarly low switching rate compared to olanzapine . Contrary to other current limited evidence , an antidepressant ( fluoxetine ) showed efficacy and did not worsen bipolar mixed depression if combined with a mood-stabilizing agent ( olanzapine ) BACKGROUND There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive . This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospect ively for an average of three years . METHOD Detailed life-charting data were obtained from 138 patients with bipolar disorder . Mood states were characterized as euthymic , subsyndromal , minor or major affective episodes based on rigorously defined criteria . The amount of time spent in these mood states during follow-up was examined . RESULTS Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic . The remainder of the time was spent in varying severity of mood states . However , the majority of time was spent with minor and subsyndromal symptoms , both manic and depressive . Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal , minor and manic symptoms . There was no difference in time spent with depressive symptoms between the two groups . CONCLUSIONS Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal . Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder 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 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 OBJECTIVES Previous studies have identified behavioral phenotypes that predispose genetically vulnerable youth to a later onset of bipolar I or II disorder , but few studies have examined whether early psychosocial intervention can reduce risk of syndromal conversion . In a one-year open trial , we tested a version of family-focused treatment adapted for youth at high risk for bipolar disorder ( FFT-HR ) . METHODS A referred sample of 13 children ( mean 13.4±2.69 years ; 4 boys , 9 girls ) who had a parent with bipolar I or II disorder participated at one of two outpatient specialty clinics . Youth met DSM-IV criteria for major depressive disorder ( n=8 ) , cyclothymic disorder ( n=1 ) , or bipolar disorder not otherwise specified ( n=4 ) , with active mood symptoms in the past month . Participants were offered FFT-HR ( 12 sessions in four months ) with their parents , plus psychotropic medications as needed . Independent evaluators assessed depressive symptoms , hypomanic symptoms , and global functioning at baseline and then every four months for one year , with retrospective severity and impairment ratings made for each week of the follow-up interval . RESULTS Families were mostly adherent to the treatment protocol ( 85 % retention ) , and therapists administered the FFT-HR manual with high levels of fidelity . Youth showed significant improvements in depression , hypomania , and psychosocial functioning scores on the Adolescent Longitudinal Interval Follow-up Evaluation . They also showed significant improvements in Young Mania Rating Scale and Children 's Depression Rating Scale scores . CONCLUSIONS FFT-HR is a promising intervention for youth at high risk for BD . Larger-scale r and omized trials that follow youth into young adulthood will be necessary to determine whether early psychosocial intervention can reduce the probability of developing bipolar I or II disorder among genetically vulnerable youth BACKGROUND The treatment of psychotic symptoms in patients with mood disorders is a complex challenge . Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms ( EPS ) , worsening of depression , and functional impairment .  Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS . The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in out patients with psychosis . METHOD In this 4-month , multicenter , open-label trial , patients were r and omly assigned in a 3:1 ratio of quetiapine to risperidone , and both drugs were flexibly dosed . Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses , including schizoaffective disorder , bipolar I disorder , major depressive disorder , delusional disorder , Alzheimer 's dementia , schizophreniform disorder , vascular dementia , and substance abuse dementia . Patients were classified as mood disordered if they had bipolar disorder , major depressive disorder , or schizoaffective disorder .  Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale . The Hamilton Rating Scale for Depression ( HAM-D ) was used to assess the level of depressive symptoms . The primary tolerability assessment was presence or absence of substantial EPS , defined as EPS severe enough to require an alteration in treatment . RESULTS A total of 554 patients were r and omly assigned to quetiapine and 175 to risperidone . Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone . Although both agents produced improvements in mean HAM-D scores , quetiapine produced a greater improvement than risperidone in all patients ( p = .0015 ) . Within the mood-diagnosed population , incidences of both substantial EPS ( p = .001 ) and at least moderate EPS ( p = .0373 ) occurred significantly less frequently among patients taking quetiapine . For patients with non-mood diagnoses , incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone ( p = .062 ) ; however , this was not statistically significant . CONCLUSION These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis OBJECTIVE To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder . METHOD The Treatment of Early Age Mania ( TEAM ) study is a multicenter , prospect i ve , r and omized , masked comparison of divalproex sodium ( VAL ) , lithium carbonate ( LI ) , and risperidone ( RISP ) in an 8-week parallel clinical trial . A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder , mixed or manic , aged 6 to 15 years were enrolled . The primary outcome measure was improvement on the Clinical Global Impression scale for depression ( CGI-BP-I-D ) . Secondary outcome measures included the Children 's Depression Rating Scale ( CDRS-R ) and suicidality status . Statistics included longitudinal analysis of outcomes using generalized linear mixed models with r and om intercept both for the complete data set and by using last observation carried forward . RESULTS CGI-BP-I-D ratings were better in the RISP group ( 60.7 % ) as compared to the LI ( 42.2 % ; p = .03 ) or VAL ( 35.0 % ; p = .003 ) groups from baseline to the end of the study . CDRS scores in all treatment groups improved equally by study end . In week 1 , scores were lower with RISP compared to VAL ( mean = 4.72 , 95 % CI = 2.67 , 6.78 ) , and compared to LI ( mean = 3.63 , 95 % CI = 1.51 , 5.74 ) , although group differences were not present by the end of the study . Suicidality was infrequent , and there was no overall effect of treatment on suicidality ratings . CONCLUSION Depressive symptoms , present in the acutely manic or mixed phase of pediatric bipolar disorder , improved with all 3 medications , though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome . Clinical trial registration information- Study of Outcome and Safety of Lithium , Divalproex and Risperidone for Mania in Children and Adolescents ( TEAM ) ; http:// clinical trials.gov ; NCT00057681 OBJECTIVE Patients with bipolar disorder have recurrent major depression , residual mood symptoms , and limited treatment options . Building on promising pilot data , the authors conducted a 6-week r and omized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression . The aims were to determine remission rate , depression symptom level , and rate of mood polarity switch , as well as to explore sleep quality . METHOD The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication ( excluding patients with hypomania or mania , mixed symptoms , or rapid cycling ) . Patients were r and omly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light ( N=23 for each group ) . Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement ( SIGH-ADS ) , the Mania Rating Scale , and the Pittsburgh Sleep Quality Index . Remission was defined as having a SIGH-ADS score of 8 or less . RESULTS At baseline , both groups had moderate depression and no hypomanic or manic symptoms . Compared with the placebo light group , the group treated with bright white light experienced a significantly higher remission rate ( 68.2 % compared with 22.2 % ; adjusted odds ratio=12.6 ) at weeks 4 - 6 and significantly lower depression scores ( 9.2 [ SD=6.6 ] compared with 14.9 [ SD=9.2 ] ; adjusted β=-5.91 ) at the endpoint visit . No mood polarity switches were observed . Sleep quality improved in both groups and did not differ significantly between them . CONCLUSIONS The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression Treatment of bipolar disorder often results in patients taking several drugs in an attempt to alleviate residual depressive symptoms , which can lead to an accumulation of side effects . New treatments for bipolar depression that do not increase the side effect burden are needed . One nonpharmacological treatment with few side effects , bright light therapy , has been shown to be an effective therapy for seasonal affective disorder , yet has not been extensively studied for other forms of depression . Forty-four adults with bipolar disorder , depressed phase were r and omized to treatment with bright light therapy , low-density or high-density negative ion generator for 8 weeks . The primary measure of efficacy was the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement ( SIGH-ADS ) . Adverse events were assessed using the Young Mania Rating Scale ( YMRS ) and Systematic Assessment for Treatment Emergent effects ( SAFTEE ) . All outcome variables were statistically analyzed using a mixed model repeated measure analysis of variance ( ANOVA ) . The results showed no statistically significant differences between groups in any outcome measures at study end point ; adverse events , including switches into hypomania , were rare . Further research is needed to determine the efficacy of bright light therapy in this population 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 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 BACKGROUND Of the 2 reports in the literature on anger attacks in bipolar depression , one found them to be uncommon ( 12 % ) compared with the rate in bipolar mixed states and unipolar depression ( 40%-60 % ) , whereas the other found them to be common ( 62 % ) . We examined anger attacks among participants in an 8-week trial of open-label citalopram  added to mood stabilizer for the treatment of bipolar depression . We also examined trait anger , hypomanic symptoms , and depressive symptoms as predictors of anger attacks . We hypothesized that if anger attacks were related to hypomanic symptoms they would respond unfavorably to citalopram , whereas if they were related to trait anger or depressive symptoms they would respond favorably . METHOD In 45 participants with a DSM-IV diagnosis of bipolar I or II depression , anger attacks , hypomanic symptoms , and depressive symptoms were assessed using a modified Anger Attacks Question naire , Young Mania Rating Scale , and Hamilton Rating Scale for Depression , respectively . Trait anger was measured using the State-Trait Anger Inventory . Posttreatment data were collected at the end of 8 weeks of treatment with citalopram or at dropout from the trial . The first participant study visit was in November 1998 , and the final participant study visit was in December 2000 . RESULTS Before treatment with citalopram , 17 ( 38.6 % ) of 44 participants reported anger attacks ( data on anger attacks were missing for 1 participant before treatment and 4 after treatment ) . Significantly fewer participants reported anger attacks after treatment ( 6 of 41 , 14.6 % ; McNemar test , p < .05 , 2-tailed ) . At pretreatment and post-treatment , trait anger was the only significant predictor of anger attacks ( p < .05 ) . CONCLUSIONS These findings suggest that in bipolar depression anger attacks are common , may respond favorably to acute treatment with citalopram added to mood stabilizer , and are better predicted by trait anger than hypomanic or depressive symptoms . Further studies are needed to clarify the diagnostic and treatment implication s of anger attacks in bipolar depression OBJECTIVE Previous studies have found that family-focused treatment is an effective adjunct to pharmacotherapy in stabilizing symptoms in adult bipolar disorder . The authors examined whether pharmacotherapy and family-focused treatment for adolescents with bipolar disorder was more effective than pharmacotherapy and brief psychoeducation ( enhanced care ) in decreasing time to recovery from a mood episode , increasing time to recurrence , and reducing symptom severity over 2 years . METHOD A total of 145 adolescents ( mean age , 15.6 years ) with bipolar I or II disorder and a DSM-IV-TR manic , hypomanic , depressive , or mixed episode in the previous 3 months were r and omly assigned , with family members , either to pharmacotherapy and family-focused treatment , consisting of psychoeducation ( i.e. , recognition and early intervention with prodromal symptoms ) , communication enhancement training , and problem-solving skills training , delivered in 21 sessions over 9 months ; or to pharmacotherapy and three weekly sessions of enhanced care ( family psychoeducation ) . Independent evaluators assessed participants at baseline , every 3 months during year 1 , and every 6 months during year 2 , using weekly ratings of mood . RESULTS Twenty-two participants ( 15.2 % ) withdrew shortly after r and omization . Time to recovery or recurrence and proportion of weeks ill did not differ between the two treatment groups . Secondary analyses revealed that participants in family-focused treatment had less severe manic symptoms during year 2 than did those in enhanced care . CONCLUSIONS After an illness episode , intensive psychotherapy combined with best- practice pharmacotherapy does not appear to confer advantages over brief psychotherapy and pharmacotherapy in hastening recovery or delaying recurrence among adolescents with bipolar disorder OBJECTIVE The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder . METHOD A 20-month , double-blind , parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex . Sixty patients were r and omly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type ( bipolar I versus bipolar II disorder ) . RESULTS Of the 254 patients enrolled in the open-label acute stabilization phase , 76 % discontinued the study prematurely ( poor adherence : 28 % ; nonresponse : 26 % [ of whom 74 % remained depressed and 26 % remained in a hypomanic/manic/mixed episode ] , intolerable side effects : 19 % ) . Of the 60 patients ( 24 % ) r and omly assigned to double-blind maintenance monotherapy , 53 % relapsed ( 59 % into depression and 41 % into a hypomanic/manic/mixed episode ) , 22 % completed the study , 10 % had intolerable side effects , and 10 % were poorly adherent . The rates of relapse into any mood episode for those given lithium versus divalproex were 56 % and 50 % , respectively ; the rates were 34 % and 29 % for a depressive relapse and 19 % and 22 % for a hypomania/mania relapse . There were no significant differences in time to relapse . The proportion discontinuing prematurely because of side effects was 16 % for lithium and 4 % for divalproex . CONCLUSIONS The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data . Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder Maintenance therapy in bipolar disorder ( BD ) is usually required to prevent relapses and improve residual symptoms . Therefore , in this study , we describe patterns of pharmacological maintenance treatment and identify associated clinical features . This prospect i ve multicentre epidemiological study recruited a cohort of 739 consecutive out- patients with clinical ly stable BD . Clinical stability was assessed at baseline with the Clinical Global Impression scale for BD and depressive symptoms with the Hamilton Depression Rating Scale .  Psychotropic medications were classified and analysed according to their mechanism as well as use . Logistic regression models were used to examine the associations between pharmacological strategies and clinical features . Longer time since last episode [ odds ratio ( OR ) 1.002 , p < 0.0001 ] and family history of psychiatric disorders ( OR 1.911 , p = 0.028 ) were associated with lithium in monotherapy ;  manic polarity of the most recent episode ( OR 3.300 , p = 0.006 ) and longer duration of clinical stability ( OR 1.009 , p = 0.034 ) with antipsychotic in monotherapy ;  depressive polarity of the most recent episode ( OR 2.567 , p = 0.003 ) and bipolar II disorder diagnosis ( OR 2.278 , p = 0.008 ) with antidepressant combination ;  no ongoing psychiatric co-morbidity ( OR 0.230 , p = 0.004 ) with lithium and anticonvulsant ;  manic polarity of the most recent episode ( OR 3.774 , p < 0.0001 ) with lithium and antipsychotic ;  manic polarity of the most recent episode ( OR 2.907 , p = 0.028 ) with lithium , anticonvulsant and antipsychotic . The pharmacological patterns followed published recommendations , except for the excessive use of antidepressants . This study reveals clinical factors closely related to prescription patterns OBJECTIVE To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD ( n = 710 ) . Those with this comorbidity who were acutely manic or in mixed states were r and omly assigned in a 6-week double-blind , placebo-controlled trial to aripiprazole ( n = 18 ) or placebo ( n = 25 ) . Primary outcome measures were assessed weekly and included the Young Mania Rating Scale ; the Swanson , Nolan , and Pelham Scale-Version IV ; and weight . Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale , the Child Mania Rating Scale-Parental Version ( CMRS-P ) , the Children 's Depression Rating Scale-Revised , the Kutcher Adolescent Depression Scale , and adverse events . The trial was conducted at the Hospital de Clínicas de Porto Alegre , Rio Gr and e do Sul , Brazil , from January 2005 to November 2007 . RESULTS The group receiving aripiprazole showed a significantly greater reduction in YMRS scores ( P = .02 , effect size [ ES ] = 0.80 ) , CMRS-P scores ( P = .02 ; ES = 0.54 ) , and CGI-S scores ( P = .04 ; ES = 0.28 ) from baseline to endpoint than the placebo group . In addition , higher rates of response ( P = .02 ) and remission ( P = .01 ) were found for the aripiprazole group . No significant between-group differences were found in weight , ADHD symptoms , and depressive symptoms . Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea . CONCLUSION Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain . No significant treatment effect in ADHD symptoms was observed . Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116259 Long-chain ω-3 polyunsaturated fatty acid ( LCn-3PUFA ) supplementation may improve symptoms of depression in children and bipolar disorder ( BD ) in adults . No studies have examined the effectiveness of LCn-3PUFA supplementation in the treatment of mania and depression in juvenile BD ( JBD ) when given as an adjunct to st and ard pharmacological treatment . Eighteen children and adolescents with JBD received supplements containing 360 mg per day eicosapentaenoic acid ( EPA ) and 1560 mg per day docosahexaenoic acid ( DHA ) for 6 weeks in an open-label study . Intake and fasting red blood cell ( RBC ) LCn-3PUFA , mania , depression and global function were assessed before and after supplementation . RBC EPA and DHA were significantly higher following supplementation . Clinician ratings of mania and depression were significantly lower and global functioning significantly higher after supplementation . Parent ratings of internalizing and externalizing behaviours were also significantly lower following supplementation . A larger r and omized controlled trial appears warranted in this participant population Aripiprazole has been approved by regulatory agencies for the treatment of schizophrenia and bipolar I disorder . Although it is a dopamine partial agonist , it also has substantial binding affinity for the serotonin 5HT2A receptor . Several double-blind r and omized clinical trials have established the efficacy and tolerability of aripiprazole within the dose range of 10–30 mg/day for schizophrenia , and 15–30 mg/day for manic or mixed states associated with bipolar I disorder . Relatively few comparative trials with other second-generation antipsychotics have been published for schizophrenia , with none available for bipolar disorder . The evidence so far suggests that in terms of efficacy for schizophrenia , aripiprazole is superior to placebo and haloperidol ( long term ) , similar to perphenazine and risperidone , and inferior to olanzapine .  Its tolerability profile in patients with schizophrenia appears superior to haloperidol , perphenazine , risperidone , and olanzapine .  Efficacy in treating manic or mixed states was established in placebo-controlled trials . Among some patients with bipolar disorder  , akathisia and gastrointestinal ( GI ) complaints can emerge at the start of treatment ; however , the GI symptoms were time-limited in many instances . Appropriate dosing may also be important in individualizing therapy to improve tolerability , with lower starting doses becoming more important when adding to , or switching from , another antipsychotic . Aripiprazole appears to have a low propensity for weight gain , a favorable metabolic profile , and no association with hyperprolactinemia BACKGROUND Offspring of parents with bipolar disorder , by virtue of their high-risk status for developing bipolar disorder , merit an investigation of the efficacy of treatment with mood stabilizers . Behavioral and mood difficulties in this population may represent prodromal forms of bipolar disorder . We studied the efficacy of divalproex in treating child and adolescent bipolar offspring with mood or behavioral disorders who did not yet meet criteria for bipolar I or II disorder . METHOD We studied 24 children aged 6 - 18 years ( mean = 11.3 years ; 17 boys/7 girls ) with at least 1 biological parent with bipolar disorder . Participants were diagnosed by the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia with at least 1 of the following DSM-IV disorders : major depressive disorder , dysthymic disorder , cyclothymic disorder , or attention-deficit/hyperactivity disorder . Subjects all had at least moderate affective symptoms ( 28-item Hamilton Rating Scale for Depression or Young Mania Rating Scale score > 12 ) . After a 2-week washout period , subjects were treated with divalproex for 12 weeks , titrated to achieve serum levels of 50 - 120 micro g/mL ( mean final dose = 821 mg/day ; mean final serum level = 79.0 micro g/mL ) . RESULTS One subject discontinued after 2 weeks due to continuation of symptoms . Of the remaining 23 subjects , 18 ( 78 % ) were considered responders by primary outcome criteria ( " very much improved " or " much improved " on the Clinical Global Impressions-Improvement scale ) . Divalproex was well tolerated with no discontinuations due to adverse effects . CONCLUSION Bipolar offspring with mood or behavioral disorders and at least mild affective symptoms may respond to divalproex treatment . Our study was limited by the open treatment , lack of a placebo group , and the heterogeneous nature of the sample . Controlled studies are warranted in the use of divalproex in symptomatic bipolar offspring BACKGROUND Psychosocial interventions for bipolar disorder are frequently unavailable and re source intensive . Mobile technology may improve access to evidence -based interventions and may increase their efficacy . We evaluated the feasibility , acceptability and efficacy of an augmentative mobile ecological momentary intervention targeting self-management of mood symptoms . METHODS This was a r and omized single-blind controlled trial with 82 consumers diagnosed with bipolar disorder who completed a four-session psychoeducational intervention and were assigned to 10 weeks of either : 1 ) mobile device delivered interactive intervention linking patient-reported mood states with personalized self-management strategies , or 2 ) paper- and -pencil mood monitoring . Participants were assessed at baseline , 6 weeks ( mid-point ) , 12 weeks ( post-treatment ) , and 24 weeks ( follow up ) with clinician-rated depression and mania scales and self-reported functioning . RESULTS Retention at 12 weeks was 93 % and both conditions were associated with high satisfaction . Compared to the paper- and -pencil condition , participants in the augmented mobile intervention condition showed significantly greater reductions in depressive symptoms at 6 and 12 weeks ( Cohen׳s d for both were d=0.48 ) . However , these effects were not maintained at 24-weeks follow up . Conditions did not differ significantly in the impact on manic symptoms or functional impairment . LIMITATIONS This was not a definitive trial and was not powered to detect moderators and mediators . CONCLUSIONS Automated mobile-phone intervention is feasible , acceptable , and may enhance the impact of brief psychoeducation on depressive symptoms in bipolar disorder . However , sustainment of gains from symptom self-management  mobile interventions , once stopped , may be limited There is growing evidence that atypical antipsychotics may be effective in the treatment of acute bipolar depression . Results from r and omized , placebo-controlled trials support the use of quetiapine monotherapy and a combination of olanzapine-fluoxetine in the depressed phase of bipolar disorder , while only limited data exists regarding the use of aripiprazole in this population . To assess the potential effectiveness of aripiprazole in treating acute bipolar depression , a chart review was conducted on 12 patients with treatment-resistant bipolar disorder ( I , II , and not otherwise specified [ NOS ] ) who received aripiprazole augmentation for the relief of an acute major depressive episode . After 8 weeks of treatment , 4 of 12 ( 33 % ) patients demonstrated a response , defined as a 50 % reduction in the Montgomery-Asberg Depression Rating Scale ( MADRS ) score . In addition , 5 of 12 ( 42 % ) patients newly developed akathisia . This report , though limited by its small sample size and naturalistic design , suggests that the usefulness of aripiprazole in the treatment of bipolar depression may be limited by akathisia Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic . Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression , but there are limited data for its use in continuation treatment . This study examined the effectiveness of open-label adjunctive quetiapine therapy for continuation treatment in patients with bipolar disorder . Prospect ively collected life chart data from 63 out patients with bipolar disorders , most recent episodes depressed , manic , or cycling , who received adjunctive quetiapine therapy as part of st and ard acute treatment were analyzed . Patients had 4 or more weeks of prequetiapine baseline data and at least 2 weeks of quetiapine treatment with no other medication changes . Patients were grouped by baseline symptoms ; depression only , mania only , or both mania and depression ( cycling group ) . Owing to small mania and well groups ( n=4 ) , differences between depression and cycling groups were examined and mania and well groups excluded . Fifty-five patients were included in the analyses . The primary outcome measure was change in mood severity from baseline to change in treatment regimen , as measured by the NIMH Life Charting Method . Patients received adjunctive quetiapine for a mean of 122 ( SD=149 ) days . Both groups showed significant improvement in depression ratings and time spent depressed by week 10 . Both groups showed significant improvement in overall mood . No between-group differences in improvement were found . Adjunctive quetiapine may be useful as continuation treatment in bipolar population s with both pure depressive and cycling symptoms . Further controlled studies are warranted BACKGROUND Many patients with bipolar disorder ( BD ) do not regain full function following an acute illness episode , but the extent to which this impairment is the result of persistent symptoms has not been well established . This study examined factors associated with persistent subsyndromal symptoms in a well characterized group of BD patients who were prospect ively followed for an average of 3 years . METHODS Detailed life charting data from 138 patients with BD were review ed . Patients were categorized into euthymic , subsyndromal or syndromal groups according to the clinical state during their most recent year of follow-up . The three groups were then examined with respect to comorbidity , function and treatment received . RESULTS Patients with subsyndromal symptoms had high rates of comorbid anxiety disorders , and were more likely to have increased rates of eating disorders as well . Patients with subsyndromal symptoms had lower global assessment of function ( GAF ) scores than euthymic patients , and had as many clinic contacts and medication trials as patients with full episodes of illness . CONCLUSIONS Persistent subsyndromal symptoms in BD patients are associated with high rates of comorbidity that is important to recognize and treat in order to optimize mood and functioning BACKGROUND Use of antipsychotic medication intermittently or over the long term may be necessary in treating patients with bipolar disorder whose symptoms have responded suboptimally to st and ard mood-stabilizing agents .  Quetiapine fumarate is an effective novel antipsychotic with mixed serotonergic ( 5-HT2 ) and dopaminergic ( D2 ) activity . This is an open-label , 12-week prospect i ve study to assess the efficacy and tolerability of quetiapine in the treatment of patients with bipolar and schizoaffective disorder who were suboptimally responsive to mood stabilizers alone . METHOD Participants in the study were in patients or out patients with a DSM-IV diagnosis of bipolar or schizoaffective disorder . Baseline psychopathology was evaluated with the Brief Psychiatric Rating Scale ( BPRS ) , the Young Mania Rating Scale ( YMRS ) , and the Hamilton Rating Scale for Depression ( HAM-D ) . Involuntary movements were rated with the Simpson-Angus Neurologic Rating Scale . Quetiapine was added on an open-label basis and increased to optimum clinical dosage . Psychopathology and Abnormal Involuntary Movement Scale ratings were repeated weekly for the first 4 weeks and then again at weeks 8 and 12 . RESULTS Ten individuals with bipolar disorder and 10 with schizoaffective disorder received quetiapine therapy . Overall , patients improved , with significant improvement in BPRS ( p < .001 ) , YMRS ( p = .043 ) , and HAM-D scores ( p = .002 ) . Simpson-Angus score also significantly decreased ( p = .02 ) . Overall . quetiapine was well tolerated by patients in this group with serious mood disorders . The mean + /- SD quetiapine dose was 202.9 + /- 124.3 mg/day ( range , 50 - 400 mg/day ) . Mean weight gain was 10.9 lb ( 4.9 kg ) . CONCLUSION Although limited by its small size , open-label design , and relative gender homogeneity , this study suggests that quetiapine therapy may be useful in the treatment of individuals with serious mood disorders who are suboptimally responsive to mood stabilizers alone . These preliminary findings should be explored in larger , controlled trials OBJECTIVES A growing number of publications describe cerebellar abnormalities in patients with bipolar disorder ( BD ) . The aim of the following paper was to examine the functional aspects of that issue by focusing on implicit learning - a cognitive function with significant cerebellar underpinnings . METHODS 27 patients with BD and 26 healthy controls ( HC ) , matched for age and sex took part in the study .  Implicit motor learning was assessed by the serial reaction time task ( SRTT ) , in which participants were unconsciously learning a sequence of motor reactions . The indicators of procedural learning were the decrease of reaction time ( RT ) across the repetition of the sequence and the rebound of RT when the sequence changed into a r and om set of stimuli . RESULTS BD patients did not present any indicators of the implicit learning , their RT increased across repetitions of the sequence and it decreased when the sequence changed to r and om . Contrary , in the control group RT decreased across the sequence repetitions and increased when the stimuli begun to appear r and omly . LIMITATIONS A low subject count and a non-drug naïve patients group , medicated with atypical antipsychotic and mood stabilizers , are the most significant limitations of this study . CONCLUSIONS BD patients did not acquire procedural knowledge while performing the task , whereas HC did . To our knowledge this is the first study that shows the impairment of implicit motor learning in patients with BD . This indicates the possible cerebellar dysfunction in this disease and may provide a new neuropsychiatric approach to bipolar disorder OBJECTIVES Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders . We addressed these issues by examining data from a prospect i ve longitudinal community study to ( i ) determine the cumulative incidence of mood episodes and disorders in the first three decades of life ; ( ii ) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa ; and ( iii ) determine the clinical and treatment characteristics of these subjects . METHODS Using the Munich-Composite International Diagnostic Interview , clinical ly trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects ( aged 14 - 24 at baseline and 21 - 34 at third follow-up ) . RESULTS The estimated cumulative incidence at age 33 was 2.9 % for manic , 4.0 % for hypomanic , 29.4 % for major depressive , and 19.0 % for minor depressive episodes ; overall , 26.0 % had unipolar major depression , 4.0 % bipolar depression , 1.5 % unipolar mania , and 3.6 % unipolar hypomania ( no major depression ) . Overall , 0.6 % and 1.8 % had unipolar mania or hypomania , respectively , without indication for even minor depression . A total of 3.6 % of the initial unipolar major depression cases subsequently developed (hypo)mania , with particularly high rates in adolescent onset depression ( < 17 years : 9 % ) . A total of 49.6 % of the initial unipolar mania cases subsequently developed major depression and 75.6 % major or minor depression . While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases , bipolar cases did not significantly differ in mania characteristics from unipolar mania cases . CONCLUSIONS Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood , a time period when both the recognition and the intervention rates by the healthcare system are rather low . ' Conversion ' to bipolar disorder is limited in initial unipolar depression , but common in initial unipolar mania . The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings
RESULTS There is sufficient evidence for a Grade A recommendation of the use of olanzapine plus fluoxetine at reducing depressive symptoms in bipolar depression and of quetiapine at high doses for depressive symptoms occurring during mixed episodes .
These results mostly overlap with the approved treatments for bipolar depression in adults
BACKGROUND The management of depressive and mixed symptoms in children and adolescents with bipolar disorder ( BD ) remains a matter of debate .
The goal of this review is , thus , to systematic ally examine the impact of atypical antipsychotics ( AAPs ) and mood stabilisers in the treatment of bipolar depression and /or mixed states .