Discontinuation of psychotropic medication: a synthesis of evidence across medication classes.

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what's the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

Do you feel up when you go up? A pilot study of a virtual reality manic-like mood induction paradigm.

OBJECTIVES: In order to understand the working mechanisms of mania, it is necessary to perform studies during the onset of manic (-like) mood states. However, clinical mania is difficult to examine experimentally. A viable method to study manic mood like states is mood induction, but mood induction tasks thus far show variable effectiveness. METHODS: In this pilot study, a new paradigm to induce mood through virtual reality (VR) is examined. Both state characteristics, namely changes in emotion, and trait characteristics, such as high and low scores on the hypomanic personality scale (HPS), were measured in 65 students. These students participated in either a neutral VR mood induction or an activating VR mood induction in which excitement, goal directedness, and tension (being aspects of mania) were induced. All participants performed a risk-taking behavioural task, Balloon Analogue Risk Task (BART). RESULTS: The experimental VR task induced excitement and tension. In participants with higher sensitivity to hypomanic personality (HPS), irritation increased in response to activation whereas it decreased in the low HPS group, and excitement increased more steeply in the low HPS group. There were no effects on the behavioural task. CONCLUSIONS: The VR task is effective in inducing relevant state aspects of hypomania and is suitable as a paradigm for future experimental studies. Activation of dual affective states (excitement and tension) is an essential aspect in manic-like mood induction paradigms.

Course of subthreshold manic symptoms and related risk factors in the general population: A three-year follow-up study.

OBJECTIVES: Subthreshold manic symptoms (subM) are a risk factor for the onset and recurrence of bipolar disorder (BD). Individuals with subM may benefit from preventive interventions, however, their development is hampered by a lack of knowledge on subM prevalence and subsequent course. This study examines subM characteristics, course, and risk factors for an unfavourable course. METHODS: In a Dutch representative, population-based sample aged 18-64 (N = 4618), we assessed subM, defined as the occurrence of manic core symptoms (elation/irritability), without meeting full DSM-IV criteria for BD I or II in the past 3 years. Comparison groups had either no manic symptoms (noM) or hypomania/mania in the context of BD (mBD) in the past 3 years. Furthermore, we differentiated a mild and moderate type of subM, based on the number of manic symptoms. A subsequent three-year course was assessed prospectively. RESULTS: SubM had a three-year prevalence of 4.9%. Its prevalence, characteristics, and course were in between noM and mBD, and there were few differences between mild and moderate subM. Over the 3-year follow-up, 25.0% of individuals with subM had persistent subM and another 6.1% transitioned to mBD. Eleven significant risk factors for this unfavourable course were found. The most important were a history of depression/dysthymia (OR 3.75, p ≤ 0.001), living alone (OR 2.61, p ≤ 0.01) and elevated neuroticism score (OR 1.21, p ≤ 0.001). CONCLUSIONS: This study supports the validity and clinical relevance of subM as a BD prodrome. It demonstrates that subM symptoms often persist or increase during follow-up and identifies 11 risk factors that are associated with an unfavourable course.

A multicomponent positive psychology intervention for euthymic patients with bipolar disorder to improve mental well-being and personal recovery: A pragmatic randomized controlled trial.

OBJECTIVE: Mental well-being and personal recovery are important treatment targets for patients with bipolar disorder (BD). The goal of this study was to evaluate the effectiveness of an 8-week group multicomponent positive psychology intervention (PPI) for euthymic patients with BD as an adjunct to treatment as usual (TAU) compared to TAU alone. METHODS: Patients with BD were randomized to receive TAU (n = 43) or the PPI in addition to TAU (n = 54). The primary outcome was well being measured with the Mental Health Continuum-Short Form. Personal recovery was measured with the Questionnaire about the Process of Recovery. Data were collected at baseline, mid-treatment, post-treatment and 6- and 12-month follow-up. Life chart interviews were conducted at 12 months to retrospectively assess recurrence of depression and mania. RESULTS: Significant group-by-time interaction effects for well-being and personal recovery were found favouring the PPI. At post-treatment, between-group differences were significant for well-being (d = 0.77) and personal recovery (d = 0.76). Between-group effects for well-being were still significant at 6-month follow-up (d = 0.72). Effects on well-being and personal recovery within the intervention group were sustained until 12-month follow-up. Survival analyses showed no significant differences in time to recurrence. CONCLUSIONS: The multicomponent PPI evaluated in this study is effective in improving mental well-being and personal recovery in euthymic patients with BD and would therefore be a valuable addition to the current treatment of euthymic BD patients. The fact that the study was carried out in a pragmatic RCT demonstrates that this intervention can be applied in a real-world clinical setting.

Bipolar I and bipolar II subtypes in older age: Results from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project.

OBJECTIVES: The distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD. METHODS: Cross-sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database. The sample included 963 participants aged ≥50 years (714 BD-I, 249 BD-II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g-score) and (3) somatic burden, with study cohort as random intercept. RESULTS: After adjustment for study cohort, BD-II patients more often had a late onset ≥50 years (p = 0.008) and more current severe depression (p = 0.041). BD-I patients were more likely to have a history of psychiatric hospitalization (p < 0.001) and current use of anti-psychotics (p = 0.003). Multivariable analyses showed that BD subtype was not related to GAF, cognitive g-score or somatic burden. CONCLUSION: BD-I and BD-II patients did not differ in terms of general functioning, cognitive impairment or somatic burden. Some clinical differences were observed between the groups, which could be the consequence of diagnostic definitions. The distinction between BD-I and BD-II is not the best way to subtype OABD patients. Future research should investigate other disease specifiers in this population.

Clinical profiles of subsequent stages in bipolar disorder: Results from the Dutch Bipolar Cohort.

INTRODUCTION: The manifestation of bipolar disorder (BD) is hypothesized to be determined by clinical characteristics such as familial loading, childhood abuse, age at onset, illness duration, comorbid psychiatric disorders, addiction, treatment resistance, and premorbid cognitive functioning. Which of these are associated with a more severe course and worse outcome is currently unknown. Our objective is to find a combination of clinical characteristics associated with advancement to subsequent stages in two clinical staging models for BD. METHODS: Using cross-sectional data from the Dutch Bipolar Cohort, staging was applied to determine the progression of bipolar-I-disorder (BD-I; N = 1396). Model A is primarily defined by recurrence of mood episodes, ranging from prodromal to chronicity. Model B is defined by level of inter-episodic functioning, ranging from prodromal to inability to function autonomously. For both models, ordinal logistic regression was conducted to test which clinical characteristics are associated with subsequent stages. RESULTS: For model A, familial loading, childhood abuse, earlier onset, longer illness duration, psychiatric comorbidity, and treatment resistance were all predictors for a higher stage in contrast to addiction and cognitive functioning. For model B, childhood abuse, psychiatric comorbidity, cognitive functioning, and treatment resistance were predictors for a more severe stage, whereas age at onset, illness duration, and addiction were not. DISCUSSION/CONCLUSIONS: Differences in clinical characteristics across stages support the construct validity of both staging models. Characteristics associated with a higher stage largely overlapped across both models. This study is a first step toward determining different clinical profiles, with a corresponding course and outcome.

Illness progression in older-age bipolar disorder: Exploring the applicability, dispersion, concordance, and associated clinical markers of two staging models for bipolar disorder in an older population.

OBJECTIVES: The validity and applicability of two existing staging models reflecting illness progression have been studied in bipolar disorder (BD) in adults, but not in older adult populations. Staging model A is primarily defined by the number and recurrence of mood episodes, model B is defined by the level of inter-episodic functioning. This study aimed to explore the applicability, dispersion, and concordance of, and associations with clinical markers in these two staging models in older-age bipolar disorder (OABD). METHODS: Using cross-sectional data from the Dutch Older Bipolars study, OABD outpatients (N = 126, ≥50 years) were staged using models A and B. Dispersion over the stages and concordance between the models were assessed. Associations were explored between model stages and clinical markers (familial loading, childhood abuse, illness duration, episode density, treatment resistance, Mini-Mental State Examination, and composite cognitive score). RESULTS: Ninety subjects could be assigned to model A, 111 to model B, 80 cases to both. The majority (61%) had multiple relapses (model A, stage 3C) but were living independently (model B, stage I-III). Concordance between models was low. For model A, the markers childhood abuse, illness duration, and episode density significantly increased over subsequent stages. Model B was not associated with a significant change in any marker. CONCLUSIONS: Assigning stages to OABD subjects was possible for both models, with age-related adjustments for model B. Model B as currently operationalized may be less suitable for OABD or may measure different aspects of illness progression, reflected by its low correspondence with model A and lack of associated clinical markers.

Cognitive performance in older-age bipolar disorder: Investigating psychiatric characteristics, cardiovascular burden and psychotropic medication.

OBJECTIVE: This study aimed to explore a large range of candidate determinants of cognitive performance in older-age bipolar disorder (OABD). METHODS: A cross-sectional study was performed in 172 BD patients aged ≥50 years. Demographics, psychiatric characteristics and psychotropic medication use were collected using self-report questionnaires and structured interviews. The presence of cardiovascular risk factors was determined by combining information from structured interviews, physical examination and laboratory assessments. Cognitive performance was investigated by an extensive neuropsychological assessment of 13 tests, covering the domains of attention, learning/ memory, verbal fluency and executive functioning. The average of 13 neuropsychological test Z-scores resulted in a composite cognitive score. A linear multiple regression model was created using forward selection with the composite cognitive score as outcome variable. Domain cognitive scores were used as secondary outcome variables. RESULTS: The final multivariable model (N = 125), which controlled for age and education level, included number of depressive episodes, number of (hypo)manic episodes, late onset, five or more psychiatric admissions, lifetime smoking, metabolic syndrome and current use of benzodiazepines. Together, these determinants explained 43.0% of the variance in composite cognitive score. Late onset and number of depressive episodes were significantly related to better cognitive performance whereas five or more psychiatric admissions and benzodiazepine use were significantly related to worse cognitive performance. CONCLUSION: Psychiatric characteristics, cardiovascular risk and benzodiazepine use are related to cognitive performance in OABD. Cognitive variability in OABD thus seems multifactorial. Strategies aimed at improving cognition in BD should include cardiovascular risk management and minimizing benzodiazepine use.

Exploring the clinical utility of two staging models for bipolar disorder.

OBJECTIVE: To assess the clinical utility of two staging models for bipolar disorder by examining distribution, correlation, and the relationship to external criteria. These are primarily defined by the recurrence of mood episodes (model A), or by intra-episodic functioning (model B). METHODS: In the Dutch Bipolar Cohort, stages according to models A and B were assigned to all patients with bipolar-I-disorder (BD-I; N = 1396). The dispersion of subjects over the stages was assessed and the association between the two models calculated. For both models, change in several clinical markers were concordant with the stage was investigated. RESULTS: Staging was possible in 87% of subjects for model A and 75% for model B. For model A, 1079 participants (93%) were assigned to stage 3c (recurrent episodes). Subdividing stage 3c with cut-offs at 5 and 10 episodes resulted in subgroups containing 242, 510, and 327 subjects. For model B, most participants were assigned to stage II (intra-episodic symptoms, N = 431 (41%)) or stage III (inability to work, N = 451 (43%)). A low association between models was found. For both models, the clinical markers "age at onset," "treatment resistance," and "episode acceleration" changed concordant with the stages. CONCLUSION: The majority of patients with BD-I clustered in recurrent stage 3 of Model A. Model B showed a larger dispersion. The stepwise change in several clinical markers supports the construct validity of both models. Combining the two staging models and sub-differentiating the recurrent stage into categories with cut-offs at 5 and 10 lifetime episodes improves the clinical utility of staging for individual patients.

The characteristics of psychotic features in bipolar disorder.

BACKGROUND: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. METHODS: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. RESULTS: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (ß = -0.09, t = -3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (ß = 0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium.

AIMS: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations. METHODS: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved. RESULTS: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence-based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey. CONCLUSIONS: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60-0.80 mmol/L with the option to reduce it to 0.40-0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80-1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40-0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65-79 years, and to maximally 0.70 mmol/L over age 80 years.

Testing a clinical staging model for bipolar disorder using longitudinal life chart data.

OBJECTIVE: Bipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages. METHODS: Using retrospectively reported longitudinal life chart data of 99 subjects from the Stanley Foundation Bipolar Network Naturalistic Follow-up Study, the occurrence, duration and timely sequence of stages 2-4 were determined per month. A multi-state model was used to calculate progression rates and identify determinants of illness progression. Stages 0, 1 and several other variables were added to the multi-state model to determine their influence on the progression rates. RESULTS: Five years after onset of BD (stage 2), 72% reached stage 3 (recurrent episodes) and 21% had reached stage 4 (continuous episodes), of whom 8% recovered back to stage 3. The progression from stage 2 to 3 was increased by a biphasic onset for both the depression-mania and the mania-depression course and by male sex. CONCLUSIONS: Staging is a useful model to determine illness progression in longitudinal life chart data. Variables influencing transition rates were successfully identified.

Psychometric properties and utility of the Responses to Positive Affect questionnaire (RPA) in a sample of people with bipolar disorder.

OBJECTIVES: To evaluate the psychometric properties of the Responses to Positive Affect (RPA) questionnaire in a sample of persons with bipolar disorder (BD). METHOD: Cross-sectional survey study with 107 persons with BD. The original 3-factor model of the RPA was compared with a 2-factor model. Construct validity was determined with measures of well-being, personal recovery, social role participation, and psychopathology and incremental validity was evaluated. RESULTS: The fit of the 3-factor model was acceptable for most fit indices. Subscores of the RPA revealed a significant relationship with aspects of well-being, personal recovery, and psychopathology. Dampening and self-focused positive rumination explained additional variance in personal recovery above and beyond well-being. CONCLUSIONS: The RPA is an internally consistent and valid tool to assess positive emotion regulation processes in persons with BD. Specifically, the processes of dampening and emotion-focused positive rumination seem to play an important role in BD.

Measuring personal recovery in people with bipolar disorder and exploring its relationship with well-being and social role participation.

The relevance of personal recovery receives increasing attention in mental health care and is also important for people with bipolar disorder (BD). There is a need for reliable and valid instruments measuring personal recovery. Therefore, the current study evaluated the psychometric properties of a Dutch translation of the Questionnaire about the Process of Recovery (QPR) in a sample of people with BD and explored the relationship with constructs of well-being, social role participation, and psychopathology. A cross-sectional survey study was conducted in which 102 people diagnosed with BD completed the QPR. Factor structure of the QPR was evaluated by conducting confirmatory factor analyses (CFA), and internal consistency was assessed by calculating reliability coefficients. Convergent validation measures assessed well-being, social role participation, and symptomatology. Incremental validity was determined by evaluating the ability of the QPR to explain variance in symptomatology above and beyond well-being. Findings of the CFA supported a unidimensional factor structure, and internal consistency estimates were excellent. Scores of the QPR showed strong correlations with convergent measures, but were only weakly associated with manic symptomatology. Moreover, personal recovery explained additional variance in symptoms of depression and anxiety above and beyond well-being, indicating incremental validity. The QPR appears to be a reliable and valid tool to assess personal recovery in people with BD. Our findings underline the importance of personal recovery in the context of treatment of BD. Personal recovery demonstrates a substantial overlap with well-being.

B-positive: a randomized controlled trial of a multicomponent positive psychology intervention for euthymic patients with bipolar disorder - study protocol and intervention development.

BACKGROUND: Bipolar disorder (BD) is characterized by recurrent (hypo)manic and depressive episodes, alternating with euthymic states in which patients are relatively symptom free. Besides clinical recovery, it is important to also strive for improvement of mental well-being and personal recovery. One prominent field focussing on the improvement of well-being is positive psychology. However, studies assessing the effects of positive psychology or personal recovery interventions for people with BD are scarce and have used weak methodological designs. The study described in this protocol article aims to assess the effectiveness of a multicomponent positive psychology intervention ("Living well with bipolar disorder") adjusted for people with BD in the euthymic phase to improve well-being and personal recovery. METHOD: The study concerns a pragmatic randomized multicenter trial. The principle objective of the study is to assess whether the positive psychology intervention offered to BD patients in remission in addition to usual care (CAU) is more effective than CAU. The study will include 112 participants randomized to either the experimental condition receiving the intervention in addition to CAU or the control condition receiving CAU. The study population are patients with BD I or II in the euthymic phase. The inclusion criteria are 1) diagnosis of BD I or BD II, 2) between the ages of 18-65, 3) four or more supportive sessions in the last year, and 4) only residual depressive or manic symptoms. Patients are excluded if they are in a depressive or manic episode, have current addiction problems or have optimal levels of well-being. Measurements take place at baseline, post-intervention and follow-up 6 and 12 months from baseline. Outcomes of measures include positive well-being, personal recovery, psychopathology, self-compassion, positive relationships, dampening of positive affect and relapse. DISCUSSION: The outlined study will be the first RCT examining the effects of a multicomponent positive psychology intervention for patients with bipolar disorder. Several limitations, including generalizability of the results and possible attrition issues, are discussed in advance. TRIAL REGISTRATION: This study has been registered in the Netherlands Trial Register ( NTR6729 ) on 12 October 2017.

Does the number of previous mood episodes moderate the relationship between alcohol use, smoking and mood in bipolar outpatients?

BACKGROUND: Evidence suggests that alcohol use and smoking are negatively associated with mood in bipolar disorders (BD). It is unknown if this relationship is moderated by the number of previous mood episodes. Therefore, this paper aims to examine whether the number of previous mood episodes moderates the relationship between alcohol use and smoking, and mood. METHOD: This study assessed the outcomes of 108 outpatients with BD I and II in a prospective observational cohort study. For 1 year, subjects daily registered mood symptoms and substance use with the prospective Life Chart Method. The relationship between the average daily consumption of alcohol and tobacco units in the whole year and mood were examined by multiple linear regression analyses. Number of previous mood episodes, grouped into its quartiles, was added as effect moderator. Outcome was the number of depressive, hypomanic and manic days in that year. RESULTS: The number of depressive days in a year increased by 4% (adjusted ß per unit tobacco = 1.040; 95% CI 1.003-1.079; p = 0.033) per unit increase in average daily tobacco consumption in that same year. Interaction analyses showed that in those subjects with less than 7 previous mood episodes, the number of manic and hypomanic days increased by 100.3% per unit increase in alcohol consumption (adjusted ß per unit alcohol = 2.003; 95% CI 1.225-3.274; p = 0.006). In those with 7 to 13 previous mood episodes, the number of manic and hypomanic days decreased by 28.7% per unit increase in alcohol consumption (adjusted ß per unit alcohol = 0.713; 95% CI 0.539-0.944; p = 0.019); and in subjects with 14 to 44 previous mood episodes, the number of manic and hypomanic days decreased by 7.2% per unit increase in tobacco consumption (adjusted ß per unit tobacco = 0.928; 95% CI 0.871-0.989; p = 0.021). CONCLUSIONS: The number of previous mood episodes moderates the relationship between alcohol use and smoking and mood; and smoking is adversely associated with the number of depressive days.

Collaborative care for patients with bipolar disorder: randomised controlled trial.

BACKGROUND: A substantial number of people with bipolar disorder show a suboptimal response to treatment. AIMS: To study the effectiveness of a collaborative care programme on symptoms and medication adherence in patients with bipolar disorder, compared with care as usual. METHOD: A two-armed, cluster randomised clinical trial was carried out in 16 out-patient mental health clinics in The Netherlands, in which 138 patients were randomised. Patient outcomes included duration and severity of symptoms and medication adherence, and were measured at baseline, 6 months and 12 months. Collaborative care comprised contracting, psychoeducation, problem-solving treatment, systematic relapse prevention and monitoring of outcomes. Mental health nurses functioned as care managers in this programme. The trial was registered with The Netherlands Trial Registry (NTR2600). RESULTS: Collaborative care had a significant and clinically relevant effect on number of months with depressive symptoms, both at 6 months (z = -2.6, P = 0.01, d = 0.5) and at 12 months (z = -3.1, P = 0.002, d = 0.7), as well as on severity of depressive symptoms at 12 months (z = -2.9, P = 0.004, d = 0.4). There was no effect on symptoms of mania or on treatment adherence. CONCLUSIONS: When compared with treatment as usual, collaborative care substantially reduced the time participants with bipolar disorder experienced depressive symptoms. Also, depressive symptom severity decreased significantly. As persistent depressive symptoms are difficult to treat and contribute to both disability and impaired quality of life in bipolar disorder, collaborative care may be an important form of treatment for people with this disorder.

Relationship of clinical course of illness variables to medical comorbidities in 900 adult outpatients with bipolar disorder.

BACKGROUND: Medical illnesses are highly comorbid with bipolar disorder, but their relationship to illness characteristics has not been previously delineated. METHODS: The incidence of 34 medical conditions and 6 poor prognosis factors (PPFs) was derived from answers to a questionnaire in over 900 outpatients with bipolar disorder who gave informed consent. The relationship of PPFs to the number of medical comorbidities was examined by Mann-Whitney U, Pearson r, and logistic regression. RESULTS: When examined individually, each of the 6 PPFs associated with an adverse course of bipolar disorder was significantly related to the number of medical comorbidities patients had. When age, gender, and independence of their relationships to each other were controlled for via regression, 3 of the PPFs remained significant (anxiety disorder, childhood abuse, and age of onset), and having 20 or more prior episodes was a strong trend. The number of PPFs was correlated with the number of comorbidities, although the above 3 PPFs show a similar magnitude of relationship. CONCLUSION: A history of childhood adversity, early age of onset of bipolar disorder, and an anxiety comorbidity were independently related to the number of medical comorbidities that patients experienced as adults. While the nature and mechanisms of this linkage remain to be further explored, the findings indicate the need for greater attention to and treatment of these 3 PPFs in hopes of ameliorating both the adverse course of bipolar illness and the burden of medical comorbidities with which they are associated.