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.
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
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 .