Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A Randomized Controlled Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Different profile of substance abuse in relation to predominant polarity in bipolar disorder: The Vitoria long-term follow-up study. Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination. Pharmacotherapy and family-focused treatment for adolescents with bipolar I and II disorders: a 2-year randomized trial. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group. Randomised controlled trial of efficacy of teaching patients with bipolar disorder to identify early symptoms of relapse and obtain treatment Daily electronic monitoring of subjective and objective measures of illness activity in bipolar disorder using smartphones– the MONARCA II trial protocol: a randomized controlled single-blind parallel-group trial Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder. Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder Impact of depressive episodes on cognitive deficits in early bipolar disorder: data from the Systematic Treatment Optimization Programme for Early Mania (STOP-EM). Antidepressant-associated switches from depression to mania in severe bipolar disorder. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders. Frequency of hospitalisations and inpatient care costs of manic episodes Lithium carbonate and imipramine in prevention of affective episodes. A comparison in recurrent affective illness. Comparison of rapid-cycling and non-rapid-cycling bipolar disorder based on prospective mood ratings in 539 outpatients. Impact of caregiver group psychoeducation on the course and outcome of bipolar patients in remission: a randomized controlled trial. Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression 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. Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.
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 Background : This study evaluated the effectiveness of adjunctive cognitive behavioral group therapy ( CBGT ) to prevent recurrence of episodes in euthymic patients with bipolar disorder . Methods : A r and omized controlled single-blind trial was conducted with 50 patients with bipolar disorder types I and II followed up for at least 12 months in an outpatient service and whose disease was in remission . An experimental CBGT manual was developed and added to treatment as usual ( TAU ) , and results were compared with TAU alone . Results : Intention-to-treat analysis showed that there was no difference between groups in terms of time until any relapse ( Wilcoxon = 0.667 ; p = 0.414 ) . When considering type of relapse , there was still no difference in either depressive ( Wilcoxon = 3.328 ; p = 0.068 ) or manic episodes ( Wilcoxon = 1.498 ; p = 0.221 ) . Although occurrence of episodes also did not differ between groups ( χ2 = 0.28 ; p = 0.59 ) , median time to relapse was longer for patients treated with CBGT compared to TAU ( Mann-Whitney = –2.554 ; p = 0.011 ) . Conclusions : Time to recurrence and number of episodes were not different in the group of patients treated with CBGT . However , median time to relapse was shorter in the TAU group . Studies with larger sample s may help to clarify whether our CBGT approach prevents new episodes of bipolar disorder . Our findings also indicated that CBGT is feasible in euthymic patients with bipolar disorder and should be investigated in future studies . To our knowledge , this is the first publication of a controlled trial of CBGT for euthymic patients with bipolar disorder BACKGROUND Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials . This double-blind , placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder . METHODS After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued , patients were r and omized to lamotrigine ( 100 - 400 mg daily ) , lithium ( 0.8 - 1.1 mEq/L ) , or placebo as double-blind maintenance treatment for as long as 18 months . RESULTS Of 349 patients who met screening criteria and entered the open-label phase , 175 met stabilization criteria and were r and omized to double-blind maintenance treatment  ( lamotrigine , 59 patients ; lithium , 46 patients ; and placebo , 70 patients ) . Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode  ( lamotrigine vs placebo , P = .02 ; lithium vs placebo , P = .006 ) . Lamotrigine was superior to placebo at prolonging the time to a depressive episode ( P = .02 ) . Lithium was superior to placebo at prolonging the time to a manic , hypomanic , or mixed episode ( P = .006 ) . The most common adverse event reported for lamotrigine was headache . CONCLUSIONS Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode . The results indicate that lamotrigine is an effective , well-tolerated maintenance treatment for bipolar disorder , particularly for prophylaxis of depression BACKGROUND There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms , especially the course of comorbid alcohol/substance abuse . METHOD A naturalistic sample of bipolar I patients ( n=120 ) was followed prospect ively for up to 10years . At baseline , number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes , respectively . 25 patients were excluded from the analyses . Outcomes including episodes , hospitalisations and suicide attempts were recorded at bimonthly visits . Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients . RESULTS Of the 95 patients analyzed , 44 ( 46.3 % ) had predominantly manic episodes and 51 ( 53.7 % ) had predominantly depressive episodes . At baseline , the predominantly depressive group had more history of suicide attempts ( 45.1 % vs. 20.5 % ; p=0.021 ) and more family history of affective disorders ( 64.7 % vs. 38.6 % ; p=0.020 ) , but they had fewer previous hospitalisations than the manic group ( mean 0.38 vs. 0.50 ; p=0.025 ) . During the 10-year follow-up , the predominantly depressive group was associated with more episodes ( p=0.001 ) , more hospitalisations ( p=0.004 ) and more suicide attempts ( p=0.002 ) . At baseline , there were no differences between the manic and depressive groups in the frequency of alcohol abuse ( 43.2 % and 35.3 % , p=0.565 ) or other substance abuse ( 13.6 % and 9.8 % , p=0.794 ) . During the 10-year follow-up , the frequency of alcohol and other substance abuse decreased significantly in the manic group only , after controlling by age at onset and civil ( marital ) status . CONCLUSION Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients , with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse . These differences should be considered when design ing treatment approaches for bipolar patients with comorbid alcohol/substance abuse In a double-blind , long-term follow-up study , 117 bipolar patients received lithium carbonate , imipramine hydrochloride , or both and 150 unipolar patients received lithium carbonate , imipramine , both lithium carbonate and imipramine , or placebo . With bipolar patients , lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes . The combination treatment provided no advantage over lithium carbonate alone . With unipolar patients , imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences . The combination treatment provided no advantage over imipramine alone . The lithium carbonate-treated group had fewer manic episodes than the other groups . Treatment outcome , which was evaluated primarily in terms of the occurrence of major depression or manic episodes , was significantly related to characteristics of the index episode , ie , the episode that brought the patient into the study 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 BACKGROUND Long-term outcomes are often poor in patients with bipolar disorder despite treatment ; more effective treatments are needed to reduce recurrences and morbidity . This study compared the efficacy of divalproex , lithium , and placebo as prophylactic therapy . METHODS A r and omized , double-blind , parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period . Patients who met the recovery criteria within 3 months of the onset of an index manic episode ( n = 372 ) were r and omized to maintenance treatment with divalproex , lithium , or placebo in a 2:1:1 ratio . Psychotropic medications were discontinued before r and omization , except for open-label divalproex or lithium , which were gradually tapered over the first 2 weeks of maintenance treatment . The primary outcome measure was time to recurrence of any mood episode . Secondary measures were time to a manic episode , time to a depressive episode , average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania , and Global Assessment of Function scores . RESULTS The divalproex group did not differ significantly from the placebo group in time to any mood episode .  Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode .  Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores . CONCLUSIONS The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy . Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures Abstract Objective : To determine the efficacy of teaching patients with bipolar disorder ( manic-depressive psychosis ) to identify early symptoms of relapse and seek prompt treatment from health services . Design : Single blind r and omised controlled trial with matching on four baseline variables using a minimisation algorithm . Setting : Mental health services in four NHS trusts ( one teaching , three non-teaching ) . Subjects : 69 patients with bipolar disorder who had had a relapse in the previous 12 months . Interventions : Seven to 12individual treatment sessions from a research psychologist plus routine care or routine care alone . Main outcome measures : Time to first manic or depressive relapse , number of manic or depressive relapses , and social functioning examined by st and ardised interviews every six months for 18 months . Results : 25th centile time to first manic relapse in experimental group was 65weeks compared with 17weeks in the control group . Event curves of time to first manic relapse significantly differed between experimental and control groups ( log rank 7.04 , df=1 , P=0.008 ) , with significant reductions in the number of manic relapses over 18months ( median difference 30 % ( 95 % confidence interval 8 % to 52 % ) , P=0.013 ) . The experimental treatment had no effect on time to first relapse or number of relapses with depression , but it significantly improved overall social functioning ( mean difference 2.0(0.7to 3.2 ) , P=0.003 ) and employment ( mean difference 0.7(0.1to 1.3 ) , P=0.030 ) by 18months . Conclusion : Teaching patients to recognise early symptoms of manic relapse and seek early treatment is associated with important clinical improvements in time to first manic relapse , social functioning , and employment Background Patients with bipolar disorder often show decreased adherence with mood stabilizers and frequently interventions on prodromal depressive and manic symptoms are delayed . Recently , the MONARCA I r and omized controlled trial investigated the effect of electronic self-monitoring using smartphones on depressive and manic symptoms . The findings suggested that patients using the MONARCA system had more sustained depressive symptoms than patients using a smartphone for normal communicative purpose s , but had fewer manic symptoms during the trial . It is likely that the ability of these self-monitored measures to detect prodromal symptoms of depression and mania may be insufficient compared to automatically generated objective data on measures of illness activity such as phone usage , social activity , physical activity , and mobility . The Monsenso system , for smartphones integrating subjective and objective measures of illness activity was developed and will be tested in the present trial . Methods The MONARCA II trial uses a r and omized controlled single-blind parallel-group design . Patients with bipolar disorder according to ICD-10 who previously have been treated at the Copenhagen Clinic for Affective Disorder , Denmark are included and r and omized to either daily use of the Monsenso system including an feedback loop between patients and clinicians ( the intervention group ) or to the use of a smartphone for normal communicative purpose s ( the control group ) for a 9-month trial period . The trial was started in September 2014 and recruitment is ongoing . The outcomes are : differences in depressive and manic symptoms ; rate of depressive and manic episodes ( primary ) ; automatically generated objective data on measures of illness activity ; number of days hospitalized ; psychosocial functioning ( secondary ) ; perceived stress ; quality of life ; self-rated depressive symptoms ; self-rated manic symptoms ; recovery ; empowerment and adherence to medication ( tertiary ) between the intervention group and the control group during the trial . Ethical permission has been obtained . Positive , neutral and negative findings will be published . Discussion If the system is effective in reducing depressive and /or manic symptoms ( and other symptoms of bipolar disorder ) and the rate of episodes , there will be basis for extending the use to the treatment of bipolar disorder in general and in larger scale . Trial registration Clinical Trials.gov NCT02221336 . Registered 26th of September 2014 OBJECTIVE The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder . METHOD Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this r and omized , placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind r and omized withdrawal period . The target asenapine dosage was 10 mg b.i.d . in the open-label period but could be titrated down to 5 mg b.i.d . After completing the open-label period , subjects meeting stabilization/stable-responder criteria were r and omized to asenapine or placebo treatment in the double-blind period . The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period . Kaplan-Meier estimation was performed , and 95 % confidence intervals were determined . Safety was assessed throughout . RESULTS A total of 549 subjects entered the open-label period , of whom 253 enrolled in the double-blind r and omized withdrawal period ( 127 in the placebo group ; 126 in the asenapine group ) .  Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects . In post hoc analyses , significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes . The most common treatment-emergent adverse events were somnolence ( 10.0 % ) , akathisia ( 7.7 % ) , and sedation ( 7.7 % ) in the open-label period and mania ( 11.9 % of the placebo group compared with 4.0 % of the asenapine group ) and bipolar I disorder ( 6.3 % compared with 1.6 % ) in the double-blind period . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated 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 BACKGROUND Although manic episodes reportedly contribute to cognitive deficits in bipolar I disorder , the contribution of depressive episodes is poorly research ed . AIMS We investigated the impact of depressive episodes on cognitive function early in the course of bipolar I disorder . METHOD A total of 68 patients and 38 controls from the Systematic Treatment Optimization Programme for Early Mania ( STOP-EM ) first-episode mania programme were examined . We conducted ( a ) a cross-sectional analysis of the impact of prior depressive episodes on baseline cognitive function and ( b ) a prospect i ve analysis assessing the contribution of depression recurrence within 1 year following a first episode of mania on cognitive functioning . RESULTS The cross-sectional analysis showed no significant differences between patients with past depressive episodes compared with those without , on overall or individual domains of cognitive function ( all P>0.09 ) . The prospect i ve analysis failed to reveal a significant group × time interaction for cognitive decline from baseline to 1 year ( P = 0.99 ) in patients with a recurrence of depressive episodes compared with those with no recurrence . However , impaired verbal memory at baseline was associated with a depression recurrence within 1 year . CONCLUSIONS Although deficits in all domains of cognitive function are seen in patients early in the course of bipolar disorder , depressive episodes do not confer additional burden on cognitive function . However , poorer verbal memory may serve as a marker for increased susceptibility to depression recurrence early in the course of illness 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 anticonvulsant lamotrigine was previously shown to be effective for bipolar depression . This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder . METHOD During an 8- to 16-week open-label phase , lamotrigine ( titrated to 200 mg/day ) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I out patients ( N = 966 ) and concomitant drugs were gradually withdrawn . Patients stabilized on open-label treatment ( N = 463 ) were then r and omly assigned to lamotrigine ( 50 , 200 , or 400 mg/day ; N = 221 ) , lithium ( 0.8 - 1.1 mEq/L ; N = 121 ) , or placebo ( N = 121 ) monotherapy for up to 18 months . The primary outcome measure was time from r and omization to intervention ( addition of pharmacotherapy ) for any mood episode ( depressive , manic , hypomanic , or mixed ) . Data were gathered from September 1997 to August 2001 . RESULTS Time to intervention for any mood episode was statistically superior ( p = .029 ) for both lamotrigine and lithium compared with placebo-median  survival times were 200 , 170 , and 93 days , respectively . Intervention for depression was more frequent than for mania by a factor of nearly 3:1 . Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode ( p = .047 ) . The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57 % , lithium 46 % , and placebo 45 % . Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode ( p = .026 ) . The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77 % , lithium 86 % , and placebo 72 % . Headache was the most frequent adverse event for all 3 treatment groups . CONCLUSION Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients , with lamotrigine predominantly effective against depression and lithium predominantly effective against mania Background We sought to test the hypothesis that antidepressants ( ADs ) may show preferential efficacy and safety among patients with type II bipolar disorder ( BD , BD-II ) more than patients with type I BD ( BD-I ) . Methods Patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , BD-I ( n = 21 ) and BD-II ( n = 49 ) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then r and omized openly to continue or discontinue ADs for up to 3 years . Outcomes were episode recurrences and changes in st and ardized symptom ratings . Results In follow-up averaging 1.64 years , both subgroups showed improvement in depressive episode frequency with AD continuation , but contrary to the hypothesis , more improvement was seen in BD-I than in BD-II ( for type II , mean [ st and ard deviation ] decrease in depressive episodes per year , 0.21 [ 0.26 ] ; for type I , mean ( SD ) decrease , 0.35 [ 0.15 ] ) . Subjects with BD-II who continued on ADs had slightly more depressive , but fewer manic/hypomanic , episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission . Conclusions The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I , except somewhat lower risk of manic/hypomanic episodes 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 Abstract Background : Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment . However , very few recent studies have investigated the economic burden of the disease . Objective : To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France . Method : A cost-of-illness study was conducted based on available data using a hospital payer perspective . The lifetime prevalence of manic episodes was estimated from published epidemiological data using a r and om-effects meta- analysis . Data were obtained by a computerised literature search using the main scientific and medical data bases . Additional epidemiological references were identified from published studies and textbooks . Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital . Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris , France for the year 1999 . Results : Extrapolating from international data on the average prevalence of bipolar I disorder , the proportion of rapid cycling patients and the average cycle duration , we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265 000 in France . Based on hospital data in Paris , the proportion of manic episodes that require hospitalisation was estimated to be around 63 % . The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs ( € 1.3 billion ) [ 1999 values ] . Conclusion : Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France . As the lifetime prevalence of bipolar I disorder may be as high as 3 % among adults , further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France Patients with recurrent affective illness ( N-122 ) were r and omly assigned to lithium carbonate , imipramine , or placebo therapy for two years following discharge from hospitalization for acute depression . Patients were classified as bipolar or unipolar based on the presence or absence of a history of mania . With bipolar patients lithium carbonate was significantly more effective than imipramine or placebo in preventing affective episodes ( ie , manic or depressive attacks severe enough to require hospitalization or use of non study drugs ) . There was a relatively high incidence of manic episodes on imipramine . Unipolar patients responded equally well to lithium carbonate or imipramine . Both treatments were significantly more effective than placebo . The difference between treatments was due primarily to depressive episodes ; manic episodes occurred infrequently and were evenly distributed across treatment groups . There was no significant difference between  lithium carbonate and imipramine  among unipolar patients OBJECTIVE To detect risk factors for rapid cycling in bipolar disorder , the authors compared characteristics of  rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective . METHOD Out patients with bipolar I disorder ( N=419 ) , bipolar II disorder ( N=104 ) , and bipolar disorder not otherwise specified ( N=16 ) were prospect ively evaluated with daily mood ratings  for 1 year . Subjects were classified as having rapid cycling ( defined by the DSM-IV criterion of four or more manic or depressive episodes within 1 year ) or not having rapid cycling , and the two groups ' demographic and retrospective and prospect i ve illness characteristics were compared . Associated factors were also evaluated in relationship to episode frequency . RESULTS Patients with rapid cycling ( N=206 ; 38.2 % ) significantly differed from those without rapid cycling ( N=333 ) with respect to the following independent variables : history of childhood physical and /or sexual abuse , bipolar I disorder subtype , number of lifetime manic or depressive episodes , history of rapid cycling , and history of drug abuse . The prevalence of these characteristics increased progressively with episode frequency . The proportion of  women  was greater than the proportion of men only among patients with eight or more episodes per year . The average time spent manic/hypomanic increased as a function of episode frequency , but the average time spent depressed was comparable in patients with one episode and in those with more than one episode . Brief episodes were as frequent as full- duration DSM-IV-defined episodes . CONCLUSIONS A number of heterogeneous risk factors were progressively associated with increasing episode frequency . Depression predominated in all bipolar disorder patients , but patients with rapid cycling were more likely to be characterized by manic features . The findings overall suggest that rapid cycling is a dimensional course specifier arbitrarily defined on a continuum of episode frequency OBJECTIVE Although there are some r and omized controlled trials that highlight the positive role of family-focused treatment added to pharmacotherapy in bipolar disorder , no trials using contemporary method ologies have analyzed the specific effect of working with caregiver-only groups . The aim of this study was to assess the efficacy of a psychoeducational group intervention focused on caregivers of euthymic bipolar patients . METHOD A total of 113 medicated euthymic bipolar out patients who lived with their caregivers were r and omized into an experimental and a control group . Caregivers in the experimental group received twelve 90-min group psychoeducation sessions focused on knowledge of bipolar disorder and training in coping skills . The patients did not attend the groups . Caregivers assigned to the control group did not receive any specific intervention . Patients were assessed monthly during both the intervention and the 12 months of follow-up . The primary outcome was time to any mood recurrence . RESULTS Psychoeducation group intervention focused on the caregivers of bipolar patients carried a reduction of the percentage of patients with any mood recurrence ( chi2 = 6.53 ; p = 0.011 ) and longer relapse-free intervals ( log-rank chi(2 ) = 4.04 ; p = 0.044 ) . When different types of episodes were analyzed separately , the effect was significant for both the number of patients who experienced a hypomanic/manic recurrence ( chi2 = 5.65 ; p = 0.017 ) and the time to such an episode ( log-rank chi2 = 5.84 ; p = 0.015 ) . The differences in preventing depressive and mixed episodes were not significant . CONCLUSIONS A psychoeducation group intervention for the caregivers of bipolar patients is a useful adjunct to usual treatment for the patients in reducing the risk of recurrences , particularly mania and hypomania , in bipolar disorder Breakthrough depression is a common problem in the treatment of bipolar disorder . Only one , recently published , double-blind , placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients . This report describes , in further detail , the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder . A r and omized , double-blind , parallel-group , multicenter study was conducted over a 52-week maintenance period . Bipolar I patients , who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode , were r and omized to maintenance treatment with divalproex , lithium , or placebo in a 2 : 1 : 1 ratio . Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase . Outcome measures were the rate of early discontinuation for depression , time to depressive relapse , proportion of patients with depressive relapse , mean change in Depressive Syndrome Scale score , proportion of patients receiving antidepressants , and time in the study . Among patients taking an antidepressant , a higher percentage of patients on placebo than divalproex discontinued early for depression .  Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period . Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance . Indices of severity of pre study illness course predicted worse outcome in all treatment groups . Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder , particularly in patients who had responded to divalproex when manic , and among patients with a more severe course of illness 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 The authors compared the efficacy of olanzapine and lithium in the prevention of  mood episode relapse/recurrence . METHOD Patients with a diagnosis of bipolar disorder ( manic/mixed ) , a history of two or more manic or mixed episodes within 6 years , and a Young Mania Rating Scale total score > or = 20 entered the study and received open-label co-treatment with olanzapine and lithium for 6 - 12 weeks . Those meeting symptomatic remission criteria ( Young Mania Rating Scale score < or = 12 ; 21-item Hamilton depression scale score < or = 8) were r and omly assigned to 52 weeks of double-blind monotherapy with olanzapine , 5 - 20 mg/day ( N=217 ) , or lithium ( target blood level : 0.6 - 1.2 meq/liter ) ( N=214 ) . RESULTS Symptomatic relapse/recurrence ( score > or = 15 on either the Young Mania Rating Scale or Hamilton depression scale ) occurred in 30.0 % of olanzapine-treated and 38.8 % of lithium-treated patients . The noninferiority of olanzapine relative to lithium ( primary objective ) in preventing relapse/recurrence was met , since the lower limit of the 95 % confidence interval on the 8.8 % risk difference ( -0.1 % to 17.8 % ) exceeded the predefined noninferiority margin ( -7.3 % ) . Secondary results showed that compared with lithium , olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence . Depression relapse/recurrence occurred in 15.7 % of olanzapine-treated and 10.7 % of lithium-treated patients . Mean weight gain during open-label co-treatment was 2.7 kg ; during double-blind monotherapy , weight gain was significantly greater with olanzapine ( 1.8 kg ) than with lithium ( -1.4 kg ) . CONCLUSIONS These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment . Both agents were comparable in preventing depression relapse/recurrence
This review shows a beneficial effect of EWS in time to recurrence , percentage of people hospitalised and functioning in people with bipolar disorder .
BACKGROUND Recurrence rates for bipolar disorder are high despite effective treatments with mood stabiliser drugs .
Self-help treatments and psychological treatments that teach patients to recognise and manage early warning symptoms and signs ( EWS ) of impending manic or depressive episodes are popular with patients .
The main aim of such interventions is to intervene early and prevent bipolar episodes , thereby increasing the time to the next recurrence and preventing hospitalisation .
OBJECTIVES To compare the effectiveness of an EWS intervention plus treatment as usual ( TAU ) versus TAU ( involving and not involving a psychological therapy ) on time to manic , depressive and all bipolar episodes ( the primary outcome ) , hospitalisation , functioning , depressive and manic symptoms .