Bipolar disorder (BD) is a chronic and recurrent illness characterized by manic, mixed or depressive episodes, alternated with periods of euthymia. Several prognostic factors are associated with higher rates of relapse, which is crucial for the identification of high-risk individuals. This study aimed at systematically reviewing the existing literature regarding the impact of sociodemographic, clinical and environmental factors, in clinical relapses, recurrences and hospitalizations due to mood episodes in BD.

A systematic search of electronic databases (PubMed, Cochrane library and Web of Science) was conducted to integrate current evidence about the impact of specific risk factors in these outcomes.

Fifty-eight articles met the inclusion criteria. Studies were grouped by the type of factors assessed. Family and personal psychiatric history, more severe previous episodes, earlier age of onset, and history of rapid cycling are associated with clinical relapses, along with lower global functioning and cognitive impairments. Unemployment, low educational status, poorer social adjustment and life events are also associated with higher frequency of episodes, and cannabis with a higher likelihood for rehospitalization.

Small sample sizes, absence of randomized clinical trials, diverse follow-up periods, lack of control for some confounding factors, heterogeneous study designs and diverse clinical outcomes.

Although current evidence remains controversial, several factors have been associated with an impaired prognosis, which might allow clinicians to identify patients at higher risk for adverse clinical outcomes and find modifiable factors. Further research is needed to elucidate the impact of each risk factor in the mentioned outcomes.

Aim of this study was to assess the cost-effectiveness and cost-utility of mindfulness-based cognitive therapy (MBCT) and treatment as usual (TAU) compared to TAU alone in adults with Bipolar disorder (BD).

An economic evaluation with a time horizon of 15 months was conducted from a societal perspective. Outcomes were expressed in costs per quality adjusted life years (QALYs) and costs per responder using the inventory of depressive symptomatology clinician rating score.

People with BD (N = 144) were included in this study. From a societal perspective, the difference of total costs between MBCT + TAU and TAU was €615, with lower costs in the MBCT + TAU group. Only healthcare costs differed significantly between the two groups. A small difference in QALYs in favor of MBCT + TAU was found combined with lower costs (-€836; baseline adjusted) for MBCT + TAU compared to TAU, resulting in a dominant incremental cost-utility ratio. The probability that the MBCT + TAU was cost-effective was 65%. All sensitivity analyses attested to the robustness of the base case analyses.

Concludingly, MBCT + TAU seems to be cost-effective compared to TAU alone, indicated by a small or neglectable difference in effect, in favor of MBCT + TAU, while resulting in lower costs.

Alcohol consumption has a key role in more than 200 diseases and health injuries, being an important factor for social and public health costs. Studies with clinical populations show an association between alcohol use disorders (AUD) and bipolar disorder. In this meta-analysis we included studies, reports, or summaries identified in Google Scholar, Lilacs, Medline, and MedCaribe that reported original data published up to 31 January 2023. We included cross-sectional and longitudinal observational studies that investigated the prevalence of AUD in patients with bipolar disorder. We calculated the prevalence rates and conducted a meta-analysis using a random effects model. The meta-analysis included 20 unique studies conducted in 12 countries, with a total sample of 32,886 individuals with bipolar disorder, comprising 17,923 women and 13,963 men, all aged 18 years or older. The prevalence of AUD in individuals with bipolar disorder was found to be 29.12%, while the prevalence of Alcohol Dependence (AD) was 15.87% and the prevalence of Alcohol Abuse (AA) was 18.74%. The high prevalence of AUD individuals with bipolar disorder is important because it highlights the need for targeted interventions to prevent and address comorbid conditions, which may improve treatment outcomes, reduce harm, and promote public health.

Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on RC-BD and extracted associated definitions, prevalence, risk-factors, and clinical outcomes. We assessed study quality (NIH Quality Assessment Tool) and levels of evidence (Oxford criteria). Of 146 identified reviews, 22 fulfilling selection criteria were included, yielding 30 studies involving 13,698 BD patients, of whom 3777 (27.6% [CI: 26.8-28.3]) were considered RC-BD, as defined in 14 reports by ≥4 recurrences/year within the past 12 months or in any year, without considering responsiveness to treatment. Random-effects meta-analytically pooled one-year prevalence was 22.3% [CI: 14.4-32.9] in 12 reports and lifetime prevalence was 35.5% [27.6-44.3] in 18 heterogenous reports. Meta-regression indicated greater lifetime prevalence of RC-BD among women than men (p=0.003). Association of RC-BD with suicide attempts, and unsatisfactory response to mood-stabilizers was supported by strong evidence (Level 1); associations with childhood maltreatment, mixed-features, female sex, and type-II BD had moderate evidence (Level 2). Other factors: genetic predisposition, metabolic disturbances or hypothyroidism, antidepressant exposure, predominant depressive polarity (Level 3), along with greater illness duration and immune-inflammatory dysfunction (Level 4) require further study. RC-BD was consistently recognized as having high prevalence (22.3%-35.5% of BD cases) and inferior treatment response. Identified associated factors can inform clinical practice. Long-term illness-course, metabolic factors, and optimal treatment require further investigation.

Comorbidity rates in Bipolar disorder rank highest among major mental disorders, especially comorbid substance use. Besides cannabis, alcohol is the most frequent substance of abuse as it is societally accepted and can be purchased and consumed legally. Estimates for lifetime comorbidity of bipolar disorder and alcohol use disorder are substantial and in the range of 40-70%, both for Bipolar I and II disorder, and with male preponderance. Alcohol use disorder and bipolarity significantly influence each other's severity and prognosis with a more complicated course of both disorders. Modern treatment concepts acknowledge the interplay between these disorders using an integrated therapy approach where both disorders are tackled in the same setting by a multi-professional team. Motivational interviewing, cognitive behavioral and socio- therapies incorporating the family and social environment are cornerstones in psychotherapy whereas the accompanying pharmacological treatment aims to reduce craving and to optimize mood stability. Adding valproate to lithium may reduce alcohol consumption whereas studies with antipsychotics or naltrexone and acamprosate did not affect mood fluctuations or drinking patterns. In summary, there is a continuous need for more research in order to develop evidence-based approaches for integrated treatment of this frequent comorbidity.

Large-scale studies on phenotypic differences between bipolar disorder type I (BDI) and type II (BDII) are scarce.

Individuals with BDI (N = 4806) and BDII (N = 3960) were compared with respect to clinical features, illness course, comorbid conditions, suicidality, and socioeconomic factors using data from the Swedish national quality assurance register for bipolar disorders (BipoläR).

BDII had higher rate of depressive episodes and more frequent suicide attempts than BDI. Furthermore, the BDII group were younger at first sign of mental illness and showed higher prevalence of psychiatric comorbidity but were more likely to have completed higher education and to be self-sustaining than the BDI group. BDII more frequently received psychotherapy, antidepressants, and lamotrigine. BDI patients had higher rate of hospitalizations and elated episodes, higher BMI, and higher rate of endocrine, nutritional, and metabolic diseases. BDI were more likely to receive mood stabilizers, antipsychotic drugs, electroconvulsive therapy, and psychoeducation.

These results demonstrate clear differences between BDI and II and counter the notion that BDII is a milder form of BDI, but rather a more complex condition with regard to clinical course and comorbidity.

Over the last three decades burgeoning research has shown that anxiety disorder comorbidity is not only highly prevalent in bipolar disorder (BD), but it also adversely impacts the course, outcome, and treatment of BD. The present review provides an overview of the current trends in research on comorbid anxiety and BDs based on prior reviews and meta-analyses (n = 103), epidemiological surveys, and large-scale clinical studies. The results reiterated the fact that at least half of those with BD are likely to develop an anxiety disorder in their lifetimes and a third of them will manifest an anxiety disorder at any point of time. All types of anxiety disorders were equally common in BD. However, there was a wide variation in rates across different sources, with most of this discrepancy being accounted for by methodological differences between reports. Comorbid anxiety disorders negatively impacted the presentation and course of BD. This unfavourable clinical profile led to poorer outcome and functioning and impeded treatment of BD. Despite the extensive body of research there was paucity of data on aetiology and treatment of anxiety disorder comorbidity in BD. Nevertheless, the substantial burden and unique characteristics of this comorbidity has important clinical and research implications.

Objective: Bipolar disorder is highly comorbid with anxiety disorders, however current and lifetime comorbidity patterns of each anxiety disorder and their associated features are not well studied. Here, we aimed to conduct a meta-analysis and meta-regression study of current evidence. Method: We searched PubMed to access relevant articles published until September 2015, using the keywords "Bipolar disorder" or "Affective Psychosis" or "manic depressive" separately with "generalized anxiety," "panic disorder," "social phobia," "obsessive compulsive," and "anxiety." Variables for associated features and prevalence of anxiety disorders were carefully extracted. Results: Lifetime any anxiety disorder comorbidity in BD was 40.5%; panic disorder (PD) 18.1%, generalized anxiety disorder (GAD) 13.3%, social anxiety disorder (SAD) 13.5% and obsessive compulsive disorder (OCD) 9.7%. Current any anxiety disorder comorbidity in BD is 38.2%; GAD is 15.2%, PD 13.3%, SAD 11.7%, and OCD 9.9%. When studies reporting data about comorbidities in BDI or BDII were analyzed separately, lifetime any anxiety disorder comorbidity in BDI and BDII were 38% and 34%, PD was 15% and 15%, GAD was 14% and 16.6%, SAD was 8% and 13%, OCD was 8% and 10%, respectively. Current any DSM anxiety disorder comorbidity in BDI or BDII were 31% and 37%, PD was 9% and 13%, GAD was 8% and 12%, SAD was 7% and 11%, and OCD was 8% and 7%, respectively. The percentage of manic patients and age of onset of BD tended to have a significant impact on anxiety disorders. Percentage of BD I patients significantly decreased the prevalence of panic disorder and social anxiety disorder. A higher rate of substance use disorder was associated with greater BD-SAD comorbidity. History of psychotic features significantly affected current PD and GAD. Conclusions: Anxiety disorder comorbidity is high in BD with somewhat lower rates in BDI vs BDII. Age of onset, substance use disorders, and percentage of patients in a manic episode or with psychotic features influences anxiety disorder comorbidity.

Reported relapse and recurrence rates in bipolar disorder (BD) differ significantly between studies. Most data originate from highly selective patients participating in sponsored randomized controlled trials with narrow inclusion criteria. To estimate the true risk of a subsequent mood episode (SME) under real-world conditions, we conducted a meta-analysis of rates of SME as reported in naturalistic BD studies.

PubMed, ScienceDirect, Scopus, and Web of Knowledge were searched until July 2015. Studies reporting the time until the emergence of an SME, from which individual data or Kaplan-Meier plots with censors marked could be retrieved, were included.

Twelve studies comprising 5,837 patients met the inclusion criteria. The median time to an SME in adults after an index episode was 1.44 years. The risk of an SME was 44% during the first year. Not having a SME during this first year lowered this risk to 19% in the second year. The risk was higher in bipolar II disorder (BD-II) than in bipolar I disorder (BD-I; HR = 1.5). In BD-I, the risk of a subsequent manic, mixed, or depressive mood episode was higher after an index episode of the same polarity (HR = 1.89-5.14). The overall risk of an SME was higher in patients with persisting subsyndromal symptoms (HR = 2.17).

The data from this study provide a more reliable estimate of the risk of an SME in BD in real-world settings. Further research into the longitudinal course of BD-II is warranted to confirm its role as a risk factor for SME.

This paper includes a short description of the important clinical aspects of Bipolar Disorder with emphasis on issues that are important for the therapeutic considerations, including mixed and psychotic features, predominant polarity, and rapid cycling as well as comorbidity.

The workgroup performed a review and critical analysis of the literature concerning grading methods and methods for the development of guidelines.

The workgroup arrived at a consensus to base the development of the guideline on randomized controlled trials and related meta-analyses alone in order to follow a strict evidence-based approach. A critical analysis of the existing methods for the grading of treatment options was followed by the development of a new grading method to arrive at efficacy and recommendation levels after the analysis of 32 distinct scenarios of available data for a given treatment option.

The current paper reports details on the design, method, and process for the development of CINP guidelines for the treatment of Bipolar Disorder. The rationale and the method with which all data and opinions are combined in order to produce an evidence-based operationalized but also user-friendly guideline and a specific algorithm are described in detail in this paper.

Suicide attempts are common in patients with bipolar disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with bipolar I disorder (BDI) versus bipolar II disorder (BDII)).

Outpatients referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype.

Among 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes.

American tertiary bipolar disorder clinic referral sample, cross-sectional design.

Further studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII.

Assess reported risk of suicide attempts by patients with bipolar disorder (BD).

Systematic searching yielded 101 reports from 22 countries (79 937 subjects). We analyzed for risk (%) and incidence rates (%/year) of attempts, comparing sex and diagnostic types, including by meta-analysis.

Attempt risk averaged 31.1% [CI: 27.9-34.3] of subjects, or 4.24 [3.78-4.70]%/year. In BD-I (43 studies) and BD-II subjects (30 studies), risks (29.9%, 31.4%) and incidence rates (4.01, 4.11%/year) were similar and not different by meta-analysis. Among women vs. men, risks (33.7% vs. 25.5%) and incidence (4.50 vs. 3.21%/year) were greater (also supported by meta-analysis: RR = 1.35 [CI: 1.25-1.45], P < 0.0001). Neither measure was related to reporting year, % women/study, or to onset or current age. Risks were greater with longer exposure, whereas incidence rates decreased with longer time at risk, possibly through 'dilution' by longer exposure.

This systematic update of international experience underscores high risks of suicide attempts among patients with BD (BD-I = BD-II; women > men). Future studies should routinely include exposure times and incidence rates by diagnostic type and sex for those who attempt suicide or not.

Bipolar disorder (BD) is a recurrent, lifelong illness with high risks of disability and excess mortality. Despite many treatment options with demonstrated short-term efficacy, evidence concerning long-term treatment effectiveness in BD remains limited and the relative value of naturalistic studies versus randomized, controlled trials (RCTs) in its assessment, uncertain. Systematic computer-searching yielded 10 naturalistic studies and 15 RCTs suitable for analysis of recurrence rates and their association with treatments and selected clinical factors. In naturalistic studies (3904 BD subjects, 53.3% women, 85.8% BD-I, mean onset age 29.1, followed up to 2.1 years), the pooled recurrence rate was 55.2% (26.3%/year). In RCTs (4828 subjects, 50.9% women, 96.0% BD-I, mean onset age 23.1, followed up to 1.9 years), the pooled recurrence rate was 39.3% (21.9%/year) with mood-stabilizing drug-treatment versus 60.6% (31.3%/year) with placebo; drug-versus-placebo outcomes favored antipsychotics over lithium, and disfavor an approved anticonvulsant. Depressive episode-polarity increased from 27.7% at intake to 52.0% at first-recurrence (p<0.0001). Recurrence rate (%/year) did not differ by study-type, was greater with younger onset and rapid-cycling, and paradoxically declined with longer observation. In short, recurrences of major affective episodes up to two years during putative mood-stabilizing treatment of BD patients in prospective, naturalistic studies and RCTs were substantial and similar (26.3 vs. 21.9%/year). Episode-polarity shifted strongly toward depressive first-recurrences. These findings support the value of naturalistic studies to complement long-term RCTs, and add to indications that control of depression in BD remains particularly unsatisfactory.

Dropout is a common problem in the treatment of psychiatric illnesses including bipolar disorders (BD). The aim of the present study is to investigate illness perceptions of dropout patients with BD. A cross sectional study was done on the participants who attended the Mood Disorder Outpatient Clinic at least 3 times from January 2003 through June 2008, and then failed to attend clinic till to the last one year, 2009, determined as dropout. Thirty-nine dropout patients and 39 attendent patients with BD were recruited for this study. A sociodemographic form and brief illness perception questionnaire were used to capture data. The main reasons of patients with BD for dropout were difficulties of transport (31%), to visit another doctor (26%), giving up drugs (13%) and low education level (59%) is significant for dropout patients. The dropout patients reported that their illness did not critically influence their lives, their treatment had failed to control their illnesses, they had no symptoms, and that their illness did not emotionally affect them. In conclusion, the nonattendance of patients with serious mental illness can result in non-compliance of therapeutic drug regimens, and a recurrence of the appearance symptoms. The perception of illness in dropout patients with BD may be important for understanding and preventing nonattendance.

The long-term outcome of bipolar disorder (BD) has been extensively investigated. However, previous studies may be biased towards hospitalized patients with bipolar I disorder (BD-I), and generalizability to the current treatment era remains uncertain. In this naturalistic study, we followed a secondary-care cohort of patients with BD.

In the Jorvi Bipolar Study, 191 patients with BD-I and bipolar II disorder (BD-II) were followed using a life-chart method. Interviews were conducted at six months, 18 months, and five years. Time to full remission, time to first recurrence, total time ill, their predictors, and BD-I versus BD-II differences were investigated among the 151 patients remaining in follow-up.

Nearly all subjects recovered from the index episode, but almost all (90%) had a recurrence, and most had multiple recurrences. The patients spent about one-third of their time in illness episodes and 15% of their time with subthreshold symptoms; half of the time they were euthymic. After controlling for confounders, no difference in time spent in depressive states between patients with BD-I and BD-II persisted. Among patients with a depressive index phase, cluster C personality disorders [hazard ratio (HR) = 0.452, p = 0.040] and higher 17-item Hamilton Depression Scale score (HR = 0.951, p = 0.022) predicted longer time to remission, whereas lifetime psychotic symptoms (HR = 2.162, p = 0.016) predicted shorter time to first recurrence.

Among patients with BD, chronicity as uninterrupted persistence of illness was rare, but multiple recurrences were the norm. Patients with BD spent only half of their time euthymic. Patients with BD-I and BD-II may differ little in proneness to depressive states. Severity of depression, cluster C personality disorders, and psychotic symptoms predicted outcome.

Bipolar disorder (BD) may result in a greater burden than all forms of cancer, Alzheimer's disease and epilepsy. Cost-of-illness (COI) studies provide useful information on the economic burden that BD imposes on a society. Furthermore, COI studies are pivotal sources of evidence used in economic evaluations. This study aims to give a general overview of COI studies for BD and to discuss methodological issues that might potentially influence results. This study also aims to provide recommendations to improve practice in this area, based on the review.

A search was performed to identify COI studies of BD. The following electronic databases were searched: MEDLINE, EMBASE, PsycInfo, Cochrane Database of Systematic Reviews, HMIC and openSIGLE. The primary outcome of this review was the annual cost per BD patient. A narrative assessment of key methodological issues was also included. Based on these findings, recommendations for good practice were drafted.

Fifty-four studies were included in this review. Because of the widespread methodological heterogeneity among included studies, no attempt has been made to pool results of different studies. Potential areas for methodological improvement were identified. These were: description of the disease and population, the approach to deal with comorbidities, reporting the rationale and impact for choosing different cost perspectives, and ways in which uncertainty is addressed.

This review showed that numerous COI studies have been conducted for BD since 1995. However, these studies employed varying methods, which limit the comparability of findings. The recommendations provided by this review can be used by those conducting COI studies and those critiquing them, to increase the credibility and reporting of study results.

Aims. Little is known about how the rates and characteristics of mental health service users in unpaid work, training and study compare with those in paid employment. Methods. From staff report and patient records, 1353 mental health service users of seven Community Mental Health Teams in two London boroughs were categorized as in paid work, unpaid vocational activity or no vocational activity. Types of work were described using Standard Occupational Classifications. The characteristics of each group were reported and associations with vocational status were explored. Results. Of the sample, 5.5% were in paid work and 12.7% were in unpaid vocational activity, (including 5.3% in voluntary work and 8.1% in study or training). People in paid work were engaged in a broader range of occupations than those in voluntary work and most in paid work (58.5%) worked part-time. Younger age and high educational attainment characterized both groups. Having sustained previous employment was most strongly associated with being in paid work. Conclusions. Rates of vocational activity were very low. Results did not suggest a clear clinical distinction between those in paid and unpaid activity. The motivations for and functions of unpaid work need further research.

Antipsychotics are commonly used in bipolar disorder, with newer (SGA) agents increasingly replacing FGA antipsychotics, particularly in bipolar depression. There are few data on differences between FGA and SGA antipsychotics in terms of their relationship to suicidal behavior in bipolar disorder.

This was a retrospective chart review of 161 bipolar veterans treated naturalistically with antipsychotics at a university-affiliated VA hospital and clinics for up to 8 years. Charts were reviewed to determine monthly antipsychotic use and occurrence of suicidal behavior: completed suicide, attempted suicide or hospitalization to prevent suicide. Suicidal behavior events were compared across patients during treatment with individual antipsychotics and FGAs or SGAs as a class.

Non-lethal suicide events were more common during FGA than SGA monotherapy (9 events/110 months of exposure vs. 6 events/381 months of exposure; χ(2)=9.65, p=0.002). Suicide event rates did not differ between FGAs and SGAs when used in conjunction with mood stabilizers. Event rates were lower with lithium than anticonvulsants when used in conjunction with antipsychotics. No differences were found between olanzapine, risperidone and quetiapine.

The retrospective chart review methodology may have led to confounding by indication and diagnostic inaccuracy. No completed suicides occurred. Study participants were primarily male veterans. Results may not be generalizable to SGAs marketed since 2003.

FGA antipsychotic monotherapy may be associated with higher suicidal behavior risk than SGA antipsychotic monotherapy. Antipsychotics used in conjunction with mood stabilizers, particularly lithium, are associated with lower rates, independent of antipsychotic subtype.

Effective, long-term therapy for bipolar disorders is a critical goal of mental health care, but achieving this goal is complicated by numerous factors in real clinical settings. The aim of this study was to investigate dropout patterns and their associated factors in patients with bipolar disorders.

The study participants were 275 patients with DSM-IV bipolar disorders, receiving planned maintenance treatment among patients at the Mood Disorders Clinic of Seoul National University Bundang Hospital between January 2005 and December 2007. The rates of dropout in patients were prospectively examined for 3 years. The factors affecting the dropouts were analyzed using a Cox regression model.

The dropout rates were 10.9%, 20.4%, 24.7%, 33.8%, 44.0%, and 50.2% at 1, 3, 6, 12, 24, and 36 months after treatment entry, respectively. The dropout rates increased rapidly during the first three months and slowed after 12 months. Past psychotic symptoms (HR 0.523, 95% CI 0.339-0.807), longer illness duration (HR 0.975, 95% CI 0.955-0.966), past psychiatric diagnoses (bipolar disorder, HR 0.242, 95% CI 0.120-0.490; other axis I disorders 0.434, 95% CI 0.268-0.701), and a past history of dropouts (HR 1.746, 95% CI 1.028-2.965) significantly influenced the time to dropout in bipolar patients. The main reasons for dropout were 'denial of therapeutic need' (34.8%) and 'lack of treatment efficacy' (23.2%). Dropout from the maintenance phase of treatment was mainly attributed to the patients' poor understanding of the effects of their treatment.

A high early dropout rate for subjects with bipolar disorders was observed in this study, suggesting an increased risk for insufficient maintenance treatment. These results may support the role of psychoeducational approaches in enhancing adherence to treatment, as well as social approaches to improving public awareness. Following the early evaluation of a patient's concept of bipolar disorders, individualized psychoeducational strategies are necessary to improve the long-term outcomes for subjects with bipolar disorders.

To characterize the extent and impact of bipolar I and II disorders and rapid cycling in a managed care population using both coded diagnostic claims and clinical screening.

The Mood Disorder Questionnaire (MDQ) was used to identify bipolar disorder among patients attending the psychiatry service of a large Midwestern health system. Suicidal ideation screening questions were also asked, along with a brief set of relevant history and medication questions. Patients scoring positive on the MDQ or identified as bipolar-positive according to DSM-IV criteria by the screening clinician were administered the Work and Social Adjustment Scale and an Employment questionnaire. Descriptive statistics were used to summarize results. The study was conducted from July 2004 to November 2004.

Seventy (6.4%) of 1087 patients had bipolar disorder, 59 of whom completed the entire study. For these patients, the mean time with bipolar disorder was 9.3 (SD 10.2) years. The mean length of the current episode was 10.4 (SD 14.4) weeks, with 22% of patients experiencing a mixed episode, 5% manic-predominant, 12% hypomanic-predominant, and 46% a depressive-predominant episode. Twenty-four percent of patients with bipolar disorder were rapid cycling at the time of their visit; for 5 of these patients, rapid cycling was thought to be related to antidepressant use. Sixty-one percent of patients with bipolar disorder were taking an antidepressant; 69.5% were taking a mood stabilizer. Of these patients with bipolar disorder, 19% were evaluated as high suicidality risk, while 47% were considered moderate risk. Bipolar disorder patients reported problems with employment/employability and social adjustment. About one quarter of these patients ranked problems with family and relationships as marked or severe. Fifty percent of these bipolar disorder patients reported missing at least 1 week of work during the past month; 41% reported fearing the loss of their current job due to their emotional state; and 20% reported being fired/laid off during the past 5 years due to their emotional state.

This research documents some of the clinical features and social and labor-force impact of bipolar disorder in a managed care population and adds several dimensions to data published to date. Fully two thirds of our study subjects with bipolar disorder were found to be at substantial risk of suicide, and bipolar disorder patients in this study reported substantial problems with employment/employability and social functioning.

Bipolar disorder is associated with a high rate of suicide attempt, and alcohol use disorders have also been associated with elevated risk for suicidal behavior. Whether risk for suicidal behavior is elevated when these conditions are comorbid has not been addressed in epidemiologic studies.

1,643 individuals with a DSM-IV lifetime diagnosis of bipolar disorder were identified from 43,093 general-population respondents who were interviewed in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Assessments were made using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). Lifetime prevalence of reported history of suicide attempt and suicidal thoughts among bipolar disorder respondents with and without DSM-IV lifetime alcohol use disorders (abuse or dependence) was assessed using chi-squared and adjusted odds ratios with confidence intervals. Logistic regression was used to test the relevance of other comorbid clinical conditions to suicide risk in bipolar respondents with and without comorbid alcohol use disorders.

More than half of the respondents (54%) who met criteria for bipolar disorder also reported alcohol use disorder. Bipolar individuals with comorbid alcohol use disorder were at greater risk for suicide attempt than those individuals without alcohol use disorder (adjusted odds ratio=2.25; 95% CI, 1.61-3.14) and were more likely to have comorbid nicotine dependence and drug use disorders. Nicotine dependence and drug use disorders did not increase risk for suicidal behavior among those with bipolar disorder, nor did they confer additional risk among bipolar respondents who also reported alcohol use disorder. Despite greater psychopathological burden, individuals with comorbid bipolar disorder and alcohol use disorder did not receive more treatment or more intensive treatment.

Suicidal behavior is more likely to occur in bipolar respondents who also suffer from alcohol use disorder. Interventions to reduce suicide risk in bipolar disorder need to address the common and high-risk comorbidity with alcohol use disorders.

To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood.

In the Jorvi Bipolar Study (JoBS), 191 secondary-care outpatients and inpatients with DSM-IV bipolar I disorder (BD-I) or bipolar II disorder (BD-II) were evaluated with the Structured Clinical Interview for DSM-IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD-I, 79 BD-II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM-IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM-IV-based scales of substance use and eating disorders.

In the SEM, depression and anxiety exhibited strong cross-sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16-0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15-0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001).

Depression and anxiety covary strongly cross-sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.

The prevalence of suicide attempts (SA) in bipolar II disorder (BPII), particularly in comparison to the prevalence in bipolar I disorder (BPI), is an understudied and controversial issue with mixed results. To date, there has been no comprehensive review of the published prevalence data for attempted suicide in BPII.

We conducted a literature review and meta-analysis of published reports that specified the proportion of individuals with BPII in their presentation of SA data. Systematic searching yielded 24 reports providing rates of SA in BPII and 21 reports including rates of SA in both BPI and BPII. We estimated the prevalence of SA in BPII by combining data across reports of similar designs. To compare rates of SA in BPII and BPI, we calculated a pooled odds ratio (OR) and 95% confidence interval (CI) with random-effect meta-analytic techniques with retrospective data from 15 reports that detailed rates of SA in both BPI and BPII.

Among the 24 reports with any BPII data, 32.4% (356/1099) of individuals retrospectively reported a lifetime history of SA, 19.8% (93/469) prospectively reported attempted suicide, and 20.5% (55/268) of index attempters were diagnosed with BPII. In 15 retrospective studies suitable for meta-analysis, the prevalence of attempted suicide in BPII and BPI was not significantly different: 32.4% and 36.3%, respectively (OR = 1.21, 95% CI: 0.98-1.48, p = 0.07).

The contribution of BPII to suicidal behavior is considerable. Our findings suggest that there is no significant effect of bipolar subtype on rate of SA. Our findings are particularly alarming in concert with other evidence, including (i) the well-documented predictive role of SA for completed suicide and (ii) the evidence suggesting that individuals with BPII use significantly more violent and lethal methods than do individuals with BPI. To reduce suicide-related morbidity and mortality, routine clinical care for BPII must include ongoing risk assessment and interventions targeted at risk factors.

We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in- and out-patients.

In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in- and out-patients, 160 patients (85.1%) could be followed up for 18 months with a life chart.

After adjusting for confounders, no marked differences in illness-related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12-16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16-0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22-3.27).

Men and women with type I and II BD have fairly similar illness-related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium-term follow-up, females appear to have a higher hazard of recurrence than males.

Bipolar patients recruited for studies are usually picked from Bipolar Disorder Units, which only contain a fraction of the total population of patients with bipolar disorder. The purpose of this study was to determine whether the course of the illness is comparable in patients from a Community Mental Health Center (CMHC) and those from a Bipolar Disorder Unit (BDU).

This study was carried out at the La Fe Teaching Hospital BDU and two CMCH. Data were collected from the patients' clinical records and were completed by a face-toface interview. When the latter was not possible, a telephone interview was carried out. Demographic, clinical and course-of-illness variables were gathered.

There were no differences in demographic characteristics between the two patient groups. Differences were found in clinical data: BDU patients were younger at illness onset (p<0.005), were admitted more frequently (p<0.05), and stayed longer in the hospital (p<0.005).

Bipolar patients treated at a CMHC show clear differences compared with those from a BDU. Consequently, care should be exercised when generalizing the clinical course of bipolar patients using BDU samples. These patients are not representative of the total bipolar patient population, as their clinical course is more complicated.

Lamotrigine (LTG) is characterized by prophylactic efficacy against bipolar depression (BPD). We evaluated retro- and prospectively the naturalistic treatment outcome with LTG analysing lifecharts of patients from the bipolar outpatient clinic.

Lifechart-data of 20 patients routinely treated with LTG for the first time were evaluated, comparing number and duration of manic, depressive and mixed episodes prior to LTG and after initiation of treatment (mirror-image evaluation). The mean prospective evaluation period based on the lifechart was 18.1 months. Also we compared the number and severity of "switches" from depression in mania. Additionally, CGI-BP, YMRS, IDS-C and GAF scores at the monthly visits were compared for time after LTG initiation.

We found no significant differences in the absolute number of manic, depressive and mixed episodes, respectively, before and after initiation of LTG. The number of "switches" did not differ significantly. A significant difference in duration of time patients suffered from a depressive state before and after initiation of LTG was observed in favour of LTG treatment (p=.006). A similar finding was observed for the time spent in mixed episodes (p<.001). No significant difference was observed for scores of mood scales at the monthly visits (CGI-BP, YMRS, IDS-C, GAF).

Generalizability of these results is limited due to the uncontrolled design and the issues in comparing prospective and retrospective data.

These data underline not only the antidepressant profile of LTG, but also the usefulness of the Lifechart-Methodology (LCM) in the evaluation of treatment outcome under routine conditions.

There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning.

A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM-IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups.

The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested.

These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.

Differences in the incidence of suicide attempts during various phases of bipolar disorder (BD), or the relative importance of static versus time-varying risk factors for overall risk for suicide attempts, are unknown.

We investigated the incidence of suicide attempts in different phases of BD as a part of the Jorvi Bipolar Study (JoBS), a naturalistic, prospective, 18-month study representing psychiatric in- and outpatients with DSM-IV BD in three Finnish cities. Life charts were used to classify time spent in follow-up in the different phases of illness among the 81 BD I and 95 BD II patients.

Compared to the other phases of the illness, the incidence of suicide attempts was 37-fold higher [95% confidence interval (CI) for relative risk (RR): 11.8-120.3] during combined mixed and depressive mixed states, and 18-fold higher (95% CI: 6.5-50.8) during major depressive phases. In Cox's proportional hazards regression models, combined mixed (mixed or depressive mixed) or major depressive phases and prior suicide attempts independently predicted suicide attempts. No other factor significantly modified the risks related to these time-varying risk factors; their population-attributable fraction was 86%.

The incidence of suicide attempts varies remarkably between illness phases, with mixed and depressive phases involving the highest risk by time. Time spent in high-risk illness phases is likely the major determinant of overall risk for suicide attempts among BD patients. Studies of suicidal behavior should investigate the role of both static and time-varying risk factors in overall risk; clinically, management of mixed and depressive phases may be crucial in reducing risk.

To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference.

In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated.

Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states.

In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II.

This study examined whether presenting diagnosis and treatment in intensive settings (hospitalization, partial hospitalization, or residential programs) are correlated with the subsequent treatment of bipolar I disorder.

Claims data were studied retrospectively (fiscal years 1994-2000) for 2,644 patients with bipolar I disorder who had been enrolled in Medicaid at least six months before their first observed bipolar diagnosis. Logistic regression models estimated the association between the presenting diagnosis and initial treatment setting and the subsequent treatment up to one year after the first observed bipolar diagnosis. Measures included receipt of guideline-recommended care (antimanic agent plus psychotherapy) or care discouraged by guidelines (an antidepressant without an antimanic agent).

Only one-third of enrollees received both guideline-recommended treatments after the first observed bipolar diagnosis. Patients were less likely to receive both recommended treatments if the first observed mental health service occurred in an intensive setting. Enrollees presenting with a bipolar diagnosis were less likely to receive psychotherapy, whereas rates of antimanic medication use were similar to those with other presenting diagnoses. Presenting with depression or anxiety or other, nonbipolar diagnoses was associated with a higher likelihood of receiving pharmacotherapy discouraged by guidelines.

This study raises general concerns for the treatment quality of bipolar I disorder in this medically complicated, largely disabled Medicaid population. Also, how bipolar I patients enter treatment can be associated with subsequent differences in treatment quality--information that can be useful to clinicians and policy makers when planning quality improvements to treatment programs.

Much controversy has surrounded the diagnosis of bipolar disorder (BD) in children and adolescents. However, recent work from an affective neuroscience perspective has advanced what is known about the boundaries of emotion regulation in BD compared to typically developing youth. In this article, we first briefly review the clinical issues that have contributed to this diagnostic controversy. Second, we discuss our phenotyping system, which can be used to guide neurobiological research designed to address these controversial issues. Third, we review what is known about the fundamentals of emotion regulation in human and nonhuman primate models. Fourth, we present recent data demonstrating how children and adolescents with BD differ from those without psychopathology on measures of emotion regulation. Taken as a whole, this work implicates a neural circuit encompassing the prefrontal cortex, amygdala, and striatum in the pathophysiology of pediatric BD.

This paper reports two studies concerned with the development and validation of the Hypomania Interpretations Questionnaire (HIQ) designed to assess positive self-dispositional appraisals for hypomania-relevant experiences.

Study 1: 203 late adolescent participants completed the HIQ along with additional measures of general symptom interpretation, dysfunctional attitudes and hypomanic personality. Study 2: 56 adults with a self-reported diagnosis of bipolar disorder and 39 controls completed a revised HIQ and a measure of current mood symptoms.

Study 1: The final 10 item HIQ had two subscales: a) positive self-dispositional appraisals (HIQ-H); and b) normalising appraisals (HIQ-NE). Internal and test-retest reliability were adequate. Hypomanic personality scores were significantly and uniquely predicted by recent hypomania-relevant experiences and HIQ-H score. Study 2: HIQ remained internally reliable within this sample. Bipolar participants (BD) reported more subsyndromal mood symptoms than controls (C) and scored significantly higher on HIQ-H even after covarying for these. HIQ-H was the primary predictor of diagnostic group. Its ability to discriminate BD from C was confirmed by ROC analysis.

The studies are cross-sectional and did not include non-bipolar psychiatric control groups.

HIQ appears to be a reliable and valid measure for the assessment of positive self-dispositional appraisals which seem to be linked to both hypomanic personality and bipolar disorder. The relevance of such appraisals for symptom exacerbation, relapse and psychological treatment would merit future investigation.

Patients (n=302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score.

YMRS score improved with quetiapine at Day 21 (-12.29 versus -8.32 for placebo; P<0.01). The difference in favor of quetiapine increased by Day 84 (-17.52 versus -9.48; P<0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P<0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day.

Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.

There has been limited research on anxiety in pediatric bipolar disorder (BPD). Adult BPD studies suggest comorbid anxiety disorders are common and impact treatment outcome. We explored the association of comorbid anxiety with two phenotypes of pediatric BPD.

We studied two groups of children. The first group (BPD; N = 31) represents the "narrow phenotype" of pediatric BPD, meeting stringent DSM-IV criteria for mania, including duration and elevated/expansive mood. The second group (ED; N = 32) exhibited chronic, non-episodic irritability without elation or grandiosity ("broad phenotype").

Both samples demonstrate high prevalence of anxiety (BPD 77.4%; ED 46.9%). In the BPD sample, anxiety predates BPD onset, and those with comorbid anxiety have earlier age of onset of BPD than those without. Children with BPD plus anxiety have more hospitalizations than those without anxiety. ED subjects with and without comorbid anxiety did not differ with respect to onset of ED symptoms or number of hospitalizations.

Narrow and broad phenotype BPD children have high rates of comorbid anxiety, although only in the narrow phenotype group is comorbid anxiety associated with greater functional impairment BPD plus comorbid anxiety may represent a particularly severe phenotype of pediatric BPD.

Different from lithium, there is little known so far on the effect of (newer) anticonvulsants on suicidality in bipolar patients. We evaluated data of 128 patients with bipolar disorders for suicidal ideation. These patients were treated with various mood-stabilizing medications for at least 3 months. No suicide attempt or completed suicide occurred in this cohort during prospective follow up for an average of 13.3 +/- 12.1 years. Compared to lithium, the relative risk of suicidal ideation was numerically slightly higher for valproate, carbamazepine and a small group treated with either levetiracetam, oxcarbazepine or topiramate, but lower in patients treated with lamotrigine, without reaching statistical significance. Confounding variables in more intensive care of these patients participating in a naturalistic study may blur small differences and contribute to a generally favorable outcome.

The course of bipolar I disorder is characterized by frequently fluctuating levels of manic and depressive symptoms. In the current study, we sought to characterize the month-by- month course of this disorder in 61 patients who were originally enrolled in a clinical trial and were followed for a mean of 23.7 months (SD = 6.1). All patients in the trial received medication management; some received family psychosocial interventions as well. On a monthly basis, we assessed symptom severity using the Modified Hamilton Rating Scale for Depression (MHRSD) and the Bech-Rafaelson Mania Scale (BRMS). Each month, we categorized each participant as fully symptomatic, partially symptomatic, or asymptomatic in terms of both depressed and manic symptoms. We found that the median percent time fully symptomatic was 8%, the median percent time partially symptomatic was 22%, and the median percent time asymptomatic was 59%. Using DSM-IV-TR criteria for defining an acute mood episode, we found that the median length of episode was 1 month, and participants experienced, on average, one episode every 8 months. Estimates concerning percent time fully symptomatic and asymptomatic converge with those reported in other datasets.

To obtain a comprehensive view of the clinical epidemiology of bipolar I and II disorder in secondary-level psychiatric settings.

In the Jorvi Bipolar Study (JoBS), 1630 non-schizophrenic psychiatric in- and outpatients in three Finnish cities were screened for bipolar I and II disorders with the Mood Disorder Questionnaire. Diagnoses were made using semistructured SCID-I and -II interviews. Information collected included clinical history, current episode, symptom status, and other characteristics.

A total of 191 patients with bipolar disorder (90 bipolar I and 101 bipolar II) were included in the JoBS. The majority of bipolar II (50.5%) and many bipolar I (25.6%) patients were previously undiagnosed; the remainder had a median 7.8 years delay from first episode to diagnosis. Despite several lifetime episodes, 26 and 58% of bipolar I and II patients, respectively, had never been hospitalized. A polyphasic episode was current in 51.3%, rapid cycling in 32.5%, and psychotic symptoms in 16.2% of patients. Mixed episodes occurred in 16.7% of bipolar I, and depressive mixed states in 25.7% of bipolar II patients.

Even in psychiatric settings, bipolar disorders usually go undetected, or recognized only after a long delay. A significant proportion of not only bipolar II, but also bipolar I patients are never hospitalized. Polyphasic episodes and rapid cycling are prevalent in both types. Depressive mixed states are at least as common among bipolar II patients as mixed episodes among bipolar I.

With costs of approximately 5.8 billion EUR annually, bipolar disorders represent a substantial burden on German society. The costs are mainly due to high indirect costs caused by morbidity-related unemployment, suicide-related losses of productivity, time off from work, and early retirement. Inpatient care, with a considerable average length of stay for patients with bipolar disorders, accounts for two-thirds of direct costs. This paper refers to statistics on use of healthcare services based primarily on the International Statistical Classification of Diseases, Tenth Revision. Representing a relatively narrow definition of bipolar disorders in comparison with the clinically relevant spectrum, this classification leads to a conservative estimate of the total costs. The significant lag between first acute episode and a correct diagnosis causes a delayed onset of maintenance treatment that leads to increased costs. Increasing public awareness, destigmatizing the disease, and educating physicians are necessary steps to limit the substantial economic burden for society.

Although patients with bipolar disorder have been shown to benefit from psychosocial interventions, the proportion that utilizes these interventions is unknown. We set out to clarify the determinants of psychosocial service utilization in adults with bipolar disorder.

We investigated psychosocial service utilization among the first 500 patients admitted to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

In the 3 months prior to enrollment in STEP-BD, a majority of the patients (54%) were engaged in at least one psychosocial service modality in addition to pharmacotherapy. In order of decreasing frequency, these were therapy with a psychologist, self-help group, therapy with a social worker, and therapy with another type of provider. Bipolar patients with personality disorders (80% vs 20%, p = 0.0002), alcohol/drug abuse disorders (76% vs 24%, p = 0.0022), and anxiety disorders (60% vs 40%, p = 0.0043) received more psychosocial services than those without. Poorer global functioning also increased the likelihood of receiving services, whereas being married decreased service utilization.

Psychosocial service utilization by outpatients with bipolar disorder is strongly linked to greater severity/complexity of illness. Potential moderators, such as insurance status and availability of care, should be examined in future studies.

To compare responses to long-term treatment of rapid-cycling (RC) vs. non-RC bipolar disorder patients and assess relative effectiveness of specific agents in RC patients.

Studies identified by literature searching were analyzed for effects of RC status and treatment-type on clinical outcome (recurrence or non-improvement per exposure-time), using random-effects methods to estimate pooled rates and their 95% CI for quantitative meta-analytic modeling.

Data were obtained from 16 reports with 25 trial-arms involving 1856 (905 RC and 951 non-RC) patients treated with carbamazepine, lamotrigine, lithium, topiramate, or valproate, alone or with other agents over an average of 47.5 months (7347 total patient-years). Estimated RC prevalence was 15.4%. Crude rates (%/month) of recurrence (2.31/1.20) and clinical non-improvement (1.93/0.49) averaged 2.9-fold greater in RC vs. non-RC subjects. The pooled RC/non-RC risk ratio (RR) for inferior treatment-response (in 13 direct comparisons) was 1.40 (CI 1.26-1.56; P < 0.0001). Pooled crude recurrence and non-improvement rates suggested no clear advantage for any treatment, nor superiority for anticonvulsants over lithium. However, only lithium vs. carbamazepine could be directly compared (in four treatment-arms) meta-analytically in RC patients (RR = 0.93, CI 0.74-1.18, indicating no difference in effectiveness).

As expected, RC was associated with lower effectiveness of all treatments evaluated. Direct comparisons of specific treatment alternatives for RC patients were rare, and provided no secure evidence of superiority of any treatment. Additional long-term studies comparing RC/non-RC patients randomized to specific treatments are required.