Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials. Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial. Open-label adjunctive topiramate in the treatment of bipolar disorders Efficacy of Topiramate, Valproate, and Their Combination on Aggression/Agitation Behavior in Patients With Psychosis Use of topiramate, a new anti-epileptic as a mood stabilizer. A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder. Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. Topiramate as an adjuvant treatment for obsessive compulsive symptoms in patients with bipolar disorder: a randomized double blind placebo controlled clinical trial. Topiramate versus Valproate Sodium as Adjunctive Therapies to a Combination of Lithium and Risperidone for Adolescents with Bipolar I Disorder: Effects on Weight and Serum Lipid Profiles Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES). Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder Integrated family and individual therapy for bipolar disorder: results of a treatment development study. Clinical factors associated with treatment noncompliance in euthymic bipolar patients. A history of substance abuse complicates remission from acute mania in bipolar disorder. Long-term symptomatic status of bipolar I vs. bipolar II disorders. Pharmacotherapy and family-focused treatment for adolescents with bipolar I and II disorders: a 2-year randomized trial. Open-Label Adjunctive Topiramate in the Treatment of Unstable Bipolar Disorder Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomised controlled trial. Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study Bipolar outcome in the course of depressive illness. Phenomenologic, familial, and pharmacologic predictors. The epidemiology of bipolar disorder: sociodemographic, disability and service utilization data from the Australian National Study of Low Prevalence (Psychotic) Disorders. Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania.
OBJECTIVE To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder . METHODS In four trials , adults hospitalized with acute mania , a diagnosis of bipolar I disorder , history of > or = 1 previous manic or mixed episodes , and > or = 20 Young Mania Rating Scale ( YMRS ) score were r and omized to double-blind treatment with topiramate ( target doses : 200 , 400 , or 600 mg/day ) or placebo ; two trials included an active comparator ( lithium , 1500 mg/day ) . The core study duration in all trials was 3 weeks ; three trials also had 9-week double-blind extensions . The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study . RESULTS Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo ( mean YMRS reductions , -5.1 to -8.4 ) . Mean YMRS reductions in lithium-treated groups were significantly greater ( p < or = 0.001 versus placebo and topiramate ) . A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions . Paresthesia , appetite decrease , dry mouth , and weight loss were more frequently associated with topiramate than with placebo . CONCLUSIONS These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder . Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression . Lithium was confirmed as an effective therapy in this population OBJECTIVE To investigate the efficacy and safety of topiramate versus placebo as adjunctive therapy for the outpatient management of bipolar I disorder . METHOD In this 12-week , r and omized , double-blind , placebo-controlled trial , adults with bipolar I disorder ( DSM-IV criteria ) experiencing a manic or mixed episode with a Young Mania Rating Scale ( YMRS ) score of > or= 18 while taking therapeutic levels of valproate or lithium received adjunctive topiramate or placebo . Topiramate was titrated from 25 to 400 mg/day over 8 weeks and was continued for 4 additional weeks . The study was conducted from October 2001 through October 2003 . The primary outcome measure was the change in YMRS score from baseline to last study visit during the double-blind phase . RESULTS The mean + /- SD change in YMRS score from baseline was -10.1 + /- 8.7 ( -40.1 % ) in the topiramate group ( N = 143 ) and -9.6 + /- 8.2 ( -40.2 % ) in the placebo group ( N = 144 , p = .797 ) . Greater than 50 % reduction in YMRS was achieved by 39 % of the topiramate group and 38 % of the placebo group ( p = .914 ) . No significant treatment differences were observed for secondary efficacy measures . Compared with adjunctive placebo , adjunctive topiramate did not worsen mania or induce depression . Paresthesia , diarrhea , and anorexia were more common in the topiramate group . The topiramate group achieved greater reductions than the placebo group in body weight ( -2.5 vs. 0.2 kg , p < .001 ) and body mass index ( -0.84 vs. 0.07 kg/m(2 ) , p < .001 ) . CONCLUSION In patients treated with lithium or valproate , there was no difference in the reduction of YMRS score in the topiramate and placebo groups . Both groups showed declines of 40 % . Topiramate reduced body weight significantly relative to placebo without worsening depressive or manic symptoms BACKGROUND To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder , we evaluated the response of 56 bipolar out patients in the Stanley Foundation Bipolar Outcome Network ( SFBN ) who had been treated with adjunctive topiramate in an open-label , naturalistic fashion . METHODS In this case series , response to topiramate was assessed every 2 weeks for the first 3 months according to st and ard ratings in the SFBN , and monthly thereafter while patients remained on topiramate .  Patients ' weights , body mass indices ( BMI s ) , and side effects were also assessed . RESULTS Of the 54 patients who completed at least 2 weeks of open-label , add-on topiramate  treatment , 30 had manic , mixed , or cycling symptoms , 11 had depressed symptoms , and 13 were relatively euthymic at the time topiramate was begun . Patients who had been initially treated for manic symptoms displayed significant reductions in st and ard ratings scores after 4 weeks , after 10 weeks , and at the last evaluation . Those patients who were initially depressed or treated while euthymic showed no significant changes . Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4 , to week 10 , and to the last evaluation . The most common adverse side effects were neurologic and gastrointestinal . CONCLUSIONS These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder , and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician . Controlled studies of topiramate 's acute and long-term efficacy and side effects in bipolar disorder appear warranted Abstract : Topiramate is an antiepileptic drug , recently also used in the treatment of psychiatric diseases . Inasmuch as topiramate and valproate , which are currently used for aggressive behavior , share several pharmacological mechanisms ( positive modulatory effect on the GABA activity and negative modulatory effect on glutamatergic neurotransmission ) , the objective of the present study was to compare the pharmacological effects of topiramate with those of valproate and their combination in patients with psychiatric disorders showing marked aggression and agitation . A retrospective , case-controlled , mirror-image study was carried out in a sample of 45 in patients affected by schizophrenia , schizoaffective and bipolar disorder , and hospitalized in a maximum-security Canadian psychiatry hospital .  Overt Aggression Scale , Agitation-Calmness Evaluation Scale , number and intensity of psychotic episodes , number of episodes of withdrawal from group activities per week , and number of therapeutic isolation per week and of strict surveillance intervention per week were evaluated before and after the treatments . Results indicate that patients treated with topiramate show a decrease in the average score of the Overt Aggression Scale , a decrease of episodes of agitation and of strict surveillance interventions . This effect was similar to the group treated with valproate or with the combination of valproate-topiramate . However , valproate therapy , but not topiramate therapy , decreased the intensity of agitation episodes measured by the Agitation-Calmness Evaluation Scale ;  valproate and the combination topiramate-valproate decreased the number of psychotic disorganization episodes as well . These results suggest that topiramate could be a valid medicine in the control of aggression in psychosis . Double-blind , r and omized , placebo-controlled studies need to further assess this pharmacological indication RATIONALE Because some anti-epileptic drugs ( AEDs ) are effective in bipolar affective disorders , the new AED topiramate ( TPM ) may be effective in psychiatric illnesses . TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs . METHODS Charts of 58 consecutive patients , 39 out patients ( 15 males , 24 females ) and 19 in patients ( 6 males , 13 females ) were review ed .  TPM 25 mg . b.i.d . was added to existing therapy and titrated in 50 mg increments every 3 - 7 days . Improvement was rated on a Likert global assessment scale of marked , moderate , mild , or no improvement or worse , based on quality of sleep , appetite , mood , and concentration . RESULTS Of the 58 patients with psychiatric disorders , 44 patients had rapid cycling bipolar disorders characterized by manic , hypomanic , or mixed episodes . Eighteen patients had previously failed to respond to lamotrigine and /or gabapentin in addition to conventional mood stabilizers . Fourteen were Bipolar I , six Bipolar II , and seven mixed , ten patients had cyclothymic disorder , seven had bipolar disorder not otherwise specified . Of the remaining 14 patients , nine had schizoaffective disorder , three patients had dementia and two had psychosis . Mean duration of TPM treatment was 16.0 weeks ; mean TPM dosage approximately 200 mg/day . Thirty-six of 58 ( 62 % ) patients exhibited marked or moderate improvement , usually within days or weeks . Twenty-three of 44 ( 52 % ) patients with bipolar affective disorders showed marked or moderate improvement . Minimal/no improvement was observed in 16 ; six were rated as worse . Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM ( 800 mg ) and tranylcypromine sulfate ( 170 mg ) combined with alcohol . Other adverse effects were minor and included : paresthesias , somnolence , fatigue , impaired concentration and memory , nausea , and diarrhoea . LIMITATIONS This study was performed in a nonr and om open and retrospective fashion . Therefore , any findings are limited by the design of this study . CONCLUSION TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation OBJECTIVE To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD This double-blind , placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy . Efficacy end points included the Young Mania Rating Scale ( YMRS ) , Brief Psychiatric Rating Scale for Children , Children 's Depression Rating Scale , Children 's Global Assessment Scale , and Clinical Global Impressions-Improvement . RESULTS Fifty-six children and adolescents ( 6 - 17 years ) with a diagnosis of bipolar disorder type I received topiramate ( n=29 , 52 % ) or placebo ( n=27 , 48 % ) . The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS ( p=.003 ) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 ( -14.9 versus-5.9 , p=.048 ) using observed data . Adverse events with topiramate included decreased appetite , nausea , diarrhea , and paresthesia . CONCLUSIONS Topiramate was well tolerated ; however , the results are inconclusive because of premature termination result ing in a limited sample size . Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents OBJECTIVE Antiepileptic drugs ( AEDs ) are commonly employed in the treatment of bipolar disorder . The efficacy and tolerability of topiramate , a novel anticonvulsant , and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions ( rater-blinded ) in patients meeting DSM-IV criteria for bipolar I/II depression . METHODS A total of 36 out- patients with Hamilton Depression Rating Scale ( HDRS-17 ) scores > or = 16 were r and omized to receive escalating doses of either topiramate ( 50 - 300 mg/day ) or bupropion SR ( 100 - 400 mg/day ) for 8 weeks . Data were analyzed on an intent-to-treat basis using the last observation carried forward method . RESULTS The percentage of patients meeting a priori response criteria ( > or = 50 % decrease from baseline in mean HDRS-17 total score ) was significant for both topiramate ( 56 % ) and bupropion SR ( 59 % ) [ t(17 ) = 2.542 , p = 0.04 and t(17 ) = 2.661 , p = 0.03 , respectively ] . Baseline demographic and clinical parameters were comparable between the two treatment groups . The mean doses of study medication were 176 mg/day ( SD = 102 mg/day ) for the topiramate-treated group and 250 mg/day ( SD = 133 mg/day ) for the bupropion SR-treated group . A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment , according to a > or = 50 % reduction in the HDRS-17 . Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups ( p = 0.001 ) , however , differences between the topiramate-treated group and the bupropion SR-treated group were not significant [ t(36 ) = 1.754 , p = 0.097 ] . Both topiramate and bupropion SR were generally well tolerated .  Thirteen patients discontinued the study : 2 because of lack of efficacy  , 1 due to withdrawal of consent and 10 following side-effects ( six in the topiramate and four in the bupropion SR-treated group ) . There were no cases of affective switch in either arm . Weight loss was experienced by patients in both groups ( mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate ) [ t(17 ) = 2.325 , p = 0.061 and t(17 ) = 2.481 , p = 0.043 , respectively ] . CONCLUSIONS These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression . The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation BACKGROUND It has not been examined trialed whether obsessive compulsive symptoms in patients with bipolar disorder respond to topiramate as an adjuvant treatment . METHODS This 4-month double-blind placebo-controlled r and omized clinical trial examined the efficacy and safety of augmentation with topiramat for treating the patients with bipolar disorder , manic phase type-I , and obsessive compulsive disorder symptoms . Both groups received lithium+olanzapine+clonazepam . However , one group received topiramate and the other group placebo as adjuvant medications . Yale Brown obsessive compulsive behavior scale was used to assess the outcome . Adverse effects were also recorded . RESULTS A total of 32 patients completed this trial . The mean score decreased from 24.2(4.8 ) to 17.6(8.7 ) in the topiramate group ( P<0.003 ) and from 20.9(2.9 ) to 9.6(3.5 ) in the placebo group during this trial ( P<0.0001 ) . Additionally , 9(52.9 % ) out of 17 patients in the topiramate group and 2(12.5 % ) out of 16 patients in the placebo group showed more than 34 % decline in YBOC score ( x2=6.0 , df=1 , P<0.01 ) . No serious adverse effects were detected . LIMITATIONS The limitations of the present study were its small sample size and the fact that it was conducted in a single center . CONCLUSIONS The combination of lithium+olanzapine+clonazepam decreased the symptoms of obsessive compulsive disorder in the patients with bipolar disorder type I. However , topiramate had a more significant effect than placebo on improvement of the patients with bipolar disorder and obsessive compulsive symptoms . This combination seems to be without serious adverse effects Objective To compare the effects of topiramate versus valproate sodium as an add-on therapy to a combination of lithium and risperidone ( Li+Ris ) on body weight and serum lipid profile in children and adolescents with bipolar disorder . Methods In a single-blind r and omized clinical trial , thirty children and adolescents with bipolar disorder type I in the manic or mixed phase , treated with the combination of Li+Ris at therapeutic doses for at least 4 weeks who had the indication of add-on therapy due to a recurrent episode ; a partial response or non response in the current episode or relapse were included . Participants were r and omly assigned to receive either topiramate or sodium valproate as the third drug add-on therapy for a total of 6 weeks . Weight , height and serum lipid profiles were determined at baseline and at the end of week 6 . Results Differences in the mean levels of lipid profiles at baseline and after week 6 evaluation were not significant in both treatment groups . BMI z-score increased in both treatment groups , being significant only in the Li+Ris/Valproate group , increasing from ( mean±SD ) 0.38±0.55 to 0.72±1.23 ( p<0.05 ) . Between group changes in BMI z-score was not significant . Among the BMI percentile categories , participants in the normal weight subgroup showed a significant increase in BMI z-score during the 6 week trial , compared to overweight/obese subgroup , in both Li+Ris/Valproate and Li+Ris/Topiramate treatment groups . Elevated mean serum level of triglyceride and a high proportion of participants with elevated total cholesterol ( ≥ 170 mg/dl ) , triglyceride ( ≥ 110 mg/dl ) , and BMI percentile 85-<95 at baseline ( before r and omization ) and at the end of 6 week study were noted . Conclusion When topiramate and valproate sodium are used for six weeks as adjunctive treatment to a combination of Li+Ris , they act alike on lipid milieu of children and adolescents with bipolar disorder . Both Li+Ris/Valproate and Li+Ris/Topiramate therapies can lead to an increase in BMI z-score . This increase is statistically significant with Li+Ris/Valproate therapy . This suggests that topiramate could attenuate the ongoing weight  gain from lithium and risperidone . In this study , the majority of participants who gained weight were those with BMI less than 85th percentile . This suggests that normal weight patients may have greater weight gain potential than overweight/obese patients .High proportion of metabolic abnormalities among the patients at baseline , which remained elevated throughout the trial , warrants cardiometabolic monitoring in this population 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 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 Several studies have established the efficacy of psychosocial interventions as adjuncts to pharmacotherapy in the symptom maintenance of bipolar disorder . This study concerned a new psychosocial approach - integrated family and individual therapy ( IFIT ) - that synthesizes family psychoeducational sessions with individual sessions of interpersonal and social rhythm therapy . METHOD Shortly after an acute illness episode , 30 bipolar patients ( DSM-IV criteria ) were assigned to open treatment with IFIT ( up to 50 weekly sessions of family and individual therapy ) and mood-stabilizing medications in the context of a treatment development study . Their outcomes over 1 year were compared with the outcomes of 70 patients from a previous trial who received st and ard community care , consisting of 2 family educational sessions , mood-stabilizing medications , and crisis management ( CM ) . Patients in both sample s were evaluated as to symptomatic functioning at entry into the project and then every 3 months for 1 year . RESULTS Patients in IFIT had longer survival intervals ( time without relapsing ) than patients in CM . They also showed greater reductions in depressive symptoms over 1 year of treatment relative to their baseline levels . The results could not be explained by group differences in baseline symptoms or pharmacologic treatment regimens . CONCLUSION Combining family and individual therapy with medication may protect episodic bipolar patients from early relapse and ongoing depressive symptoms . Further examination of this integrative model within r and omized controlled trials is warranted BACKGROUND Noncompliance with medication is a very common feature among bipolar patients . Rates of poor compliance may reach 64 % for bipolar disorders , and noncompliance is the most frequent cause of recurrence . Knowledge of the clinical factors associated with noncompliance would enhance clinical management and the design of strategies to achieve a better outcome for bipolar patients . Although most patients withdraw from medication during maintenance treatment , compliance studies in euthymic bipolar sample s are scarce . METHOD Compliance treatment and its clinical correlates were assessed at the end of 2-year follow-up in 200 patients meeting Research Diagnostic Criteria for bipolar I or bipolar II disorder by means of compliance-focused interviews , measurements of plasma concentrations of mood stabilizers  , and 2 structured interviews : the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM-III-R Axis II disorders . Well-compliant patients and poorly compliant patients were compared with respect to several clinical and treatment variables . RESULTS The rate of mildly and poorly compliant patients was close to 40 % . Comorbidity with personality disorders was strongly associated with poor compliance . Poorly compliant patients had a higher number of previous hospitalizations , but reported fewer previous episodes . The type of treatment was not associated with compliance . CONCLUSION Clinical factors , especially comorbidity with personality disorders , are more relevant for treatment compliance than other issues such as the nature of pharmacologic treatment . Compliant patients may have a better outcome in terms of number of hospitalizations , but not necessarily with respect to the number of episodes . Bipolar patients , especially those with personality disorders , should be monitored for treatment compliance BACKGROUND Substance abuse frequently complicates the course of bipolar illness , promotes mixed states , and contributes to poor outcome in mania . Preliminary open trials suggest that anticonvulsant mood stabilizers may enhance remission rates and outcome for bipolar patients with substance abuse . This study compared remission patterns for mixed or pure manic episodes among bipolar in patients with or without substance abuse histories . METHOD Hospital records were retrospectively review ed for 204 DSM-III-R bipolar I in patients . Clinical features were compared for those with or without substance abuse/dependence histories predating the index manic episode . Time until remission was analyzed by Kaplan-Meier survival analysis . Naturalistic treatment outcome with lithium or anticonvulsant mood stabilizers was compared for those with or without past substance abuse . RESULTS Past substance abuse was evident in 34 % of the bipolar sample and comprised most often alcoholism ( 82 % ) , followed by cocaine ( 30 % ) , marijuana ( 29 % ) , sedative-hypnotic or amphetamine ( 21 % ) , and opiate ( 13 % ) abuse . Substance abuse was more common among men ( p < .05 ) and those with mixed rather than pure mania ( p < .05 ) . Remission during hospitalization was less likely among patients with prior substance abuse ( p < .05 ) , especially alcohol or marijuana abuse , and among mixed manic patients with past substance abuse ( p < .05 ) . Bipolar patients with substance abuse histories who received divalproex or carbamazepine  remitted during hospitalization more often than did those who received lithium as the sole mood stabilizer ( p < .05 ) . CONCLUSION These findings support previous reports suggesting that bipolar patients with past substance abuse have poorer naturalistic treatment outcomes , but may show a better response to anticonvulsant mood stabilizers than lithium Weekly affective symptom severity and polarity were compared in 135 bipolar I ( BP I ) and 71 bipolar II ( BP II ) patients during up to 20 yr of prospect i ve symptomatic follow-up . The course of BP I and BP II was chronic ; patients were symptomatic approximately half of all follow-up weeks ( BP I 46.6 % and BP II 55.8 % of weeks ) . Most bipolar disorder research has concentrated on episodes of MDD and mania and yet minor and subsyndromal symptoms are three times more common during the long-term course . Weeks with depressive symptoms predominated over manichypomanic symptoms in both disorders ( 31 ) in BP I and BP II at 371 in a largely depressive course ( depressive symptoms=59.1 % of weeks vs. hypomanic=1.9 % of weeks ) . BP I patients had more weeks of cyclingmixed polarity , hypomanic and subsyndromal hypomanic symptoms . Weekly symptom severity and polarity fluctuated frequently within the same bipolar patient , in which the longitudinal symptomatic expression of BP I and BP II is dimensional in nature involving all levels of affective symptom severity of mania and depression . Although BP I is more severe , BP II with its intensely chronic depressive features is not simply the lesser of the bipolar disorders ; it is also a serious illness , more so than previously thought ( for instance , as described in DSM-IV and ICP-10 ) . It is likely that this conventional view is the reason why BP II patients were prescribed pharmacological treatments significantly less often when acutely symptomatic and during intervals between episodes . Taken together with previous research by us on the long-term structure of unipolar depression , we su bmi t that the thrust of our work during the past decade supports classic notions of a broader affective disorder spectrum , bringing bipolarity and recurrent unipolarity closer together . However the genetic variation underlying such a putative spectrum remains to be clarified 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 : To assess open-label adjunctive topiramate in the treatment of out patients with unstable bipolar disorder ( BD ) . Method : Out patients with DSM-IV – defined BD ( I or II ) exhibiting mood instability were enrolled in this 16-week , open-label , multicentre study . Topiramate was added to existing mood stabilizers and other psychotropic treatments . The primary effectiveness measure was the Clinical Global Impression of Severity ( CGI-S ) scale ; other scales included the Young Mania Rating Scale ( YMRS ) and the Montgomery – Asberg Depression Rating Scale ( MADRS ) . Safety assessment s included monitoring adverse events , measuring tremor , monitoring vital signs and weight , and laboratory indices . We also evaluated patient satisfaction with treatment . Results : A total of 109 patients were enrolled . Intent-to-treat analysis showed significant improvement from baseline in the CGI-S , YMRS , and MADRS , starting at Week 2 ( P < 0.001 ) , with further accrual of benefit between Week 2 and Week 16 ( P < 0.001 ) . The mean modal dosage of topiramate during the stable dosing period was 180 mg daily . There was a mean 1.8 kg decrease in patient weight  from topiramate initiation to Week 16 ( P < 0.001 ) . Topiramate was well tolerated by most patients ; 11 % withdrew from the study owing to adverse events . We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment ( P < 0.005 ) ; no notable changes in vital signs were observed . At Week 16 , 50 % of the patients were “ completely satisfied ” with topiramate treatment . Conclusions : Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms , as well as reducing tremor and weight in out patients with BD I or II BACKGROUND Efficacy trials suggest that structured psychological therapies may significantly reduce recurrence rates of major mood episodes in individuals with bipolar disorders . AIMS To compare the effectiveness of treatment as usual with an additional 22 sessions of cognitive-behavioural therapy ( CBT ) . METHOD We undertook a multicentre , pragmatic , r and omised controlled treatment trial ( n=253 ) . Patients were assessed every 8 weeks for 18 months . RESULTS More than half of the patients had a recurrence by 18 months , with no significant differences between groups ( hazard ratio=1.05 ; 95 % CI 0.74 - 1.50 ) . Post hoc analysis demonstrated a significant interaction ( P=0.04 ) such that adjunctive CBT was significantly more effective than treatment as usual in those with fewer than 12 previous episodes , but less effective in those with more episodes . CONCLUSIONS People with bipolar disorder and comparatively fewer previous mood episodes may benefit from CBT . However , such cases form the minority of those receiving mental healthcare Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania . The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting . Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study . In order to assess the efficacy and the extrapyramidal symptoms ( EPS ) , the Young Mania Rating Scale ( YMRS ) , Clinical Global Impression ( CGI ) and Simpson-Angus Rating Scale ( SARS ) were measured at the baseline and at weeks 1 , 3 and 6 . From the baseline to the endpoint , the YMRS and CGI scores were reduced by 67.9 % and 56.6 % in the topiramate plus risperidone group ( TPMG ) . The YMRS and CGI scores were also reduced by 63.7 % and 58.2 % in the divalproex plus risperidone group ( DVPG ) . The weight and body mass index ( BMI ) increased significantly by 3.6 % and 3.3 % from the baseline to the endpoint in the DVPG , while they decreased by 0.5 % and 0.4 % , respectively , with no significant difference in the TPMG . There were no serious adverse events in either group . Despite the method ological limitations , topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer ( MS ) such as divalproex Twenty percent of a cohort of 206 outpatient depressives with no past bipolar history switched during prospect i ve observation . These 41 prob and s developed manic periods on the average of 6.4 years ( median 4 , range 1 - 25 ) after their first depressive episode . The change in polarity occurred throughout the life span , but was most common in adolescence and early adulthood . The following variables were found useful in predicting this outcome : onset less than or equal to 25 years , bipolar family history , loaded pedigrees , precipitation by childbirth , hypersomnic-retarded phenomenology , and pharmacologically-mobilized hypomania . Although the respective sensitivities of these findings were relatively low ( 32 - 71 % ) , their specificities ranged from 69 % to 100 % for bipolar outcome ; the diagnostic specificity of any 3 of these variables when combined was 98 % . When compared with nonbipolar depression , bipolar disorder was seldom chronologically secondary to nonaffective psychiatric disorders . These findings suggest that many young depressives with lethargy and oversleeping are not manifesting a " neurotic " disorder , but rather a precursor of primary bipolar affective disorder . Finally , a psychotically depressed adolescent or young adult with positive bipolar family history should be observed for eventual bipolar outcome , especially when the clinical presentation is that of stupor OBJECTIVES Data from the Australian National Study of Low Prevalence ( Psychotic ) Disorders were used to describe the clinical and sociodemographic profile of individuals with bipolar disorder , their levels of impairment and disability , and use of medication and treatment services .  METHODS A 1-month census of contacts with mental health services , private psychiatric and general practice s , as well as contact points in marginalized setting s , was conducted in a national catchment of 1.1 million adults . The census yielded 3,800 individuals who screened positive for psychosis , of whom a r and om sample of 980 were administered a comprehensive semi-structured interview schedule . Results are presented on 112 persons with an ICD-10 diagnosis of bipolar disorder . RESULTS Overall , 69.6 % of the 112 persons who met the ICD-10 criteria for bipolar disorder reported a recurrent episodic illness , 25.0 % had a chronic course without clear remissions , and 5.4 % had a single episode of mania . Assessed on a lifetime basis , suicidal ideation was common ( 78.6 % ) and levels of drug and alcohol abuse/dependence were high ( 32.1 % ) . The majority ( 84.8 % ) had had at least one contact with inpatient , outpatient or emergency services in the previous year . Those with serious impairment had levels of service utilization similar to the rest of the sample , but were more likely to report a poorer quality of life and unmet service needs . While the percentage experiencing social and occupational dysfunction was substantial and similar for both sexes , women appeared to be better integrated socially than men . Comparisons with schizophrenia patients within the same survey sample highlighted less chronic impairment but equal or greater utilization of services by bipolar patients . CONCLUSIONS Despite low levels of chronicity , the burden of social disablement associated with bipolar disorder is high . The data suggest a number of important gaps in the provision of services for this predominantly treated population Background The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder . Methods A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed , with the combination of the words ' aripiprazole ' and ' bipolar ' . Results The search returned 184 articles and was last up date d on 15 April 2009 . An additional search included repositories of clinical trials and previous systematic review s specifically in order to trace unpublished trials . There were seven placebo-controlled r and omised controlled trials ( RCTs ) , six with comparator studies and one with add-on studies . They assessed the usefulness of aripiprazole in acute mania , acute bipolar depression and during the maintenance phase in comparison to placebo , lithium or haloperidol . Conclusion Aripiprazole appears effective for the treatment and prophylaxis against mania . The data on bipolar depression are so far negative , however there is a need for further study at lower dosages . The most frequent adverse effects are extrapyramidal signs and symptoms , especially akathisia , without any significant weight gain , hyperprolactinaemia or laboratory test changes OBJECTIVE The therapeutics for bipolar disorders are still far from adequate , and new options with improved effectiveness , safety , and tolerability in a wide range of patients are necessary . Preliminary data have suggested a role for dysfunctions targeting the purinergic system in mood disorders . This study aim ed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania . METHOD A r and omized , placebo-controlled , double-blind study was performed in adult in patients ( N = 180 ) with a DSM-IV-TR diagnosis of bipolar I disorder , current episode manic with or without psychotic features ( rapid cyclers and mixed episodes were not included ) . No antipsychotic agent was used during the study . Subjects were given fixed oral doses of either allopurinol 600 mg/day ( N = 60 ) , dipyridamole 200 mg/day ( N = 60 ) , or placebo ( N = 60 ) added to lithium for 4 weeks . Subjects were rated at baseline and days 7 , 14 , 21 , and 28 using the Young Mania Rating Scale ( YMRS ) as the primary efficacy measure . The study was conducted between September 2003 and September 2006 . RESULTS Allopurinol result ed in greater mean reductions in YMRS scores from baseline to day 21 ( p < .001 ) and day 28 ( p = .003 ) compared with placebo using a linear model analysis ( d = 0.32 , 95 % CI = 0.07 to 0.57 ) . Remission rates were significantly higher for allopurinol compared with dipyridamole and placebo ( p = .008 ) . Lithium showed a significant antimanic efficacy even in the placebo group . Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group ( p < .001 ) . CONCLUSION Allopurinol is clinical ly effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania , especially for those presenting tolerability and safety issues with antipsychotics . The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of bipolar disorder . Further placebo-controlled studies with allo-purinol compared with st and ard mood stabilizers in mania and maintenance are warranted . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00560079
It is not possible to draw any firm conclusions about the use of topiramate in clinical practice from this evidence .
BACKGROUND Bipolar disorder is a common recurrent illness with high levels of chronicity .
Previous trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder .
This is an up date of a previous Cochrane review ( last published 2006 ) on the role of topiramate in bipolar disorder .
OBJECTIVES To assess the effects of topiramate for acute mood episodes  in bipolar disorder in adults compared to placebo , alternative pharmacological treatment , and combination pharmacological treatment as measured by treatment of symptoms on specific rating scales for individual episodes .