The impact of body mass index on the clinical features of bipolar disorder: A STEP-BD study.

INTRODUCTION: The effects of body mass index (BMI) on the core symptoms of bipolar disorder (BD) and its implications for disease trajectory are largely unexplored. OBJECTIVE: To examine whether BMI impacted hospitalization rate, medical and psychiatric comorbidities, and core symptom domains such as depression and suicidality in BD. METHODS: Participants (15 years and older) were 2790 BD outpatients enrolled in the longitudinal STEP-BD study; all met DSM-IV criteria for BD-I, BD-II, cyclothymia, BD NOS, or schizoaffective disorder, bipolar subtype. BMI, demographic information, psychiatric and medical comorbidities, and other clinical variables such as bipolarity index, history of electroconvulsive therapy (ECT), and history of suicide attempts were collected at baseline. Longitudinal changes in Montgomery-Åsberg Depression Rating Scale (MADRS) score, Young Mania Rating Scale (YMRS) score, and hospitalizations during the study were also assessed. Depending on the variable of interest, odds-ratios, regression analyses, factor analyses, and graph analyses were applied. RESULTS: A robust increase in psychiatric and medical comorbidities was observed, particularly for baseline BMIs >35. A significant relationship was noted between higher BMI and history of suicide attempts, and individuals with BMIs >40 had the highest prevalence of suicide attempts. Obese and overweight individuals had a higher bipolarity index (a questionnaire measuring disease severity) and were more likely to have received ECT. Higher BMIs correlated with worsening trajectory of core depression symptoms and with worsening lassitude and inability to feel. CONCLUSIONS: In BD participants, elevated BMI was associated with worsening clinical features, including higher rates of suicidality, comorbidities, and core depression symptoms.

Clozapine and the Course of Bipolar Disorder in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

OBJECTIVE: The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two groups, one that received olanzapine and an additional group that received neither drug. METHOD: A total of 4,032 outpatients were available for this analysis. Groups for longitudinal analyses are based on the medication used at each visit. Outcomes assessed were clinical status, symptoms subscales, hospitalizations, and death. We utilized mixed models and generalized estimating equations to adjust for baseline differences and investigate longitudinal differences in symptoms, clinical status, and hospitalization rates between groups. RESULTS: During the study, 1.1% (n = 43) of the patients used clozapine at any time. Those on clozapine had significantly fewer manic and depressive symptoms during follow-up as compared with those on neither clozapine nor olanzapine, while those on olanzapine had more symptoms. The use of clozapine was not associated with an increased risk of hospitalization. No deaths were recorded for clozapine group during the trial. CONCLUSIONS: Although prescribed to very few patients, the impact of clozapine was notable, with fewer symptoms in patients who had more severe illnesses at baseline. Clozapine could prove to be as successful an intervention for late-stage bipolar disorder as it has been in schizophrenia.

An evaluation of the impact of co-occurring anxiety and substance use disorder on bipolar disorder illness outcomes in STEP-BD.

BACKGROUND: Anxiety disorder (AD) and substance use disorder (SUD) highly co-occur with bipolar disorder (BD). AD and/or SUD co-occurrence is associated with poorer clinical outcomes in BD. However, respective associations between AD and/or SUD diagnoses and BD outcomes require clarification. Baseline data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were therefore utilized to investigate independent and simultaneous contributions of ADs and SUDs on clinical variables in BD. METHODS: Two latent factors, "pathological anxiety" and "substance use problems," were derived from presence/absence of lifetime AD and SUD diagnoses. Latent dimensions' associations with clinical variables, obtained from the Affective Disorders Evaluation, Mini-International Neuropsychiatric Interview and Range of Impaired Functioning, were estimated via structural equation modeling (SEM). RESULTS: Modeled independently, pathological anxiety and substance use problems were significantly associated with several variables. Yet when modeled simultaneously, pathological anxiety's associations with functional impairment, past-year rapid cycling, and past-year %time spent anxious and depressed remained while most variables' associations with substance use problems became non-significant. The only significant latent-factor interaction evidenced was for age of BD onset. LIMITATIONS: Analyses were limited to lifetime diagnoses and causality may not be inferred given cross-sectional data. CONCLUSIONS: ADs and SUDs impact on BD was mostly additive rather than synergistic. Findings highlight the potentially understated importance of treating inter-episodic anxiety in BD as it may exacerbate mood symptoms, increasing functional impairment and risk for subsequent mood episodes.

Revisiting the canons of psychiatry: Teaching the fundamentals of CATIE, STAR*D, and STEP-BD to family medicine residents.

Family medicine physicians are often the first providers to encounter and identify mental illness in their patients. Having a solid understanding of three landmark studies-Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), Sequenced Treatment Alternatives to Relieve Depression (STAR*D), and Systemic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)-can significantly improve a family medicine physician's approach to mental illness and treatment choices, ultimately improving patient outcomes. Each of these studies has generated dozens of publications and consolidating the fundamentals of each one is essential for a resident to retain and implement findings in a real-world setting when treating patients with schizophrenia, depression, and bipolar disorder. When presented at the 38th Forum for Behavioral Science in Family Medicine in Chicago, IL, in September 2017, learners answered pre- and post-presentation questions about the treatment and guidelines pertaining to the three studies. Discussion leaders-physicians double-boarded in family medicine and psychiatry-presented key findings, clinical guidelines generated from each study, and updates since their respective publications. At the conclusion of the talk, participants received access to a slide deck and one-page summary for use in teaching at their home residency programs. Here, we present a framework for teaching family medicine residents three important canons of psychiatry with the goal of better management of three commonly encountered mental illnesses in the primary care setting.

An item response theory evaluation of the young mania rating scale and the montgomery-asberg depression rating scale in the systematic treatment enhancement program for bipolar disorder (STEP-BD).

BACKGROUND: The Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) are among the most widely used outcome measures for clinical trials of medications for Bipolar Disorder (BD). Nonetheless, very few studies have examined the measurement characteristics of the YMRS and MADRS in individuals with BD using modern psychometric methods. The present study evaluated the YMRS and MADRS in the Systematic Treatment Enhancement Program for BD (STEP-BD) study using Item Response Theory (IRT). METHODS: Baseline data from 3716 STEP-BD participants were available for the present analysis. The Graded Response Model (GRM) was fit separately to YMRS and MADRS item responses. Differential item functioning (DIF) was examined by regressing a variety of clinically relevant covariates (e.g., sex, substance dependence) on all test items and on the latent symptom severity dimension, within each scale. RESULTS: Both scales: 1) contained several items that provided little or no psychometric information, 2) were inefficient, in that the majority of item response categories did not provide incremental psychometric information, 3) poorly measured participants outside of a narrow band of severity, 4) evidenced DIF for nearly all items, suggesting that item responses were, in part, determined by factors other than symptom severity. LIMITATIONS: Limited to outpatients; DIF analysis only sensitive to certain forms of DIF. CONCLUSIONS: The present study provides evidence for significant measurement problems involving the YMRS and MADRS. More work is needed to refine these measures and/or develop suitable alternative measures of BD symptomatology for clinical trials research.

Family history of a mood disorder indicates a more severe bipolar disorder.

BACKGROUND: In the clinical setting, patients with bipolar disorder (BD) are often asked about potential family history (FH) of mood disorders. The aim of the present study was to examine differences between BD patients with FH of a mood disorder, and those without, on clinical, personality and social functioning characteristics, as well as on the symptomatic course of the disorder. METHODS: Data was collected from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). For this report, we included 2600 patients, 1963 of those reported having a first-degree family member with a mood disorder, and 637 reported of no such FH. We investigated the impact of FH on socio-demographic, clinical, personality and quality of life variables, as well as on symptomatology during the first year of treatment. RESULTS: Patients reporting FH of a mood disorder had an earlier age at onset of depression/mania, more phases, rapid cycling and more suicide attempts. Across different assessments, patients with FH showed consistently elevated depressive symptoms, such as lower concentration and energy, higher suicidal ideation, as well as increased racing thoughts and distractibility within the manic spectrum of symptoms. Further, the FH group had lower quality of life, higher neuroticism and higher personality disorder scores compared to patients without FH. LIMITATIONS: Information on FH was obtained through the proband. CONCLUSIONS: Overall, BD patients reporting FH of a mood disorder showed a worse clinical profile upon presentation for treatment and a more symptomatic course of the disorder.

Clinical, psychological and environmental predictors of prospective suicide events in patients with Bipolar Disorder.

Patients with Bipolar Disorder (BD) have high rates of suicide compared to the general population. The present study investigates the predictive power of baseline clinical, psychological and environmental characteristics as risk factors of prospective suicide events (attempts and completions). Data was collected from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. 3083 bipolar patients were included in this report, among these 140 (4.6%) had a suicide event (8 died by suicide and 132 attempted suicide). Evaluation and assessment forms were used to collect clinical, psychological and socio-demographic information. Chi-square and independent t-tests were used to evaluate baseline characteristics. Potential prospective predictors were selected on the basis of prior literature and using a screening analysis of all risk factors that were associated with a history of suicide attempt at baseline and were tested using a Cox regression analysis. The strongest predictor of a suicide event was a history of suicide attempt (hazard ratio = 2.60, p-value < 0.001) in line with prior literature. Additional predictors were: younger age, a high total score on the personality disorder questionnaire and a high percentage of days spent depressed in the year prior to study entry. In conclusion, the present findings may help clinicians to identify patients at high risk for suicidal behavior upon presentation for treatment.

Revisión del Programa para la Mejoría Sistemática del Tratamiento del Trastorno Bipolar (STEP-BD) / Revision of systematic treatment enhancement program for bipolar disorder (STEP-BD)

El programa STEP-BD es una iniciativa pública que surge de la necesidad de tener datos sobre el trastorno bipolar obtenidos en entornos de investigación pragmáticos o de la vida real. Los objetivos primarios son: investigar la efectividad de las intervenciones terapéuticas en el trastorno bipolar, el impacto en el curso de la enfermedad de estas intervenciones en entornos pragmáticos o de la vida real y aumentar el conocimiento sobre la enfermedad. Incluyó, en seis años, a 4361 pacientes. Este programa no es un estudio en fases, es una infraestructura compuesta por más de 40 estudios publicados y 30 presentaciones en congresos. Estos estudios tienen por objetivo captar la heterogeneidad de la enfermedad en sus presentaciones clínicas, tratamiento, comorbilidades, funcionalidad y calidad de vida. Los pacientes que ingresan al programa tuvieron una evaluación común. El programa consta de dos ramas principales: tratamiento estándar y tratamientos randomizados de depresión bipolar aguda, depresión bipolar refractaria y prevención de recaídas. Además, diversos estudios completan el programa en un intento de darle coherencia a las diferentes presentaciones clínicas de esta enfermedad, a los diferentes tratamientos y las diferentes intervenciones para fenómenos clínicos similares.

The STEP-BD is a public initiative, created to generate data, obtained in pragmatic or real life research environments, from the bipolar disorder. The primary objectives are: to investigate the effectiveness of therapeutic interventions in bipolar disorder, the impact on the disease course of these interventions in the "real life" and to raise the knowledge about the disease. This program included in six years, n = 4361 patients. This program is not a study in phases but an infrastructure for more than 40 published studies and 30 conference presentations. These studies aim to capture the heterogeneity of the disease in their different clinical presentations, treatments, comorbidities, functionality and quality of life. Patients entering the program have a common assessment. The program consists of two main pathways: the standard treatment and randomized treatment of acute bipolar depression, bipolar depression and refractory relapse prevention. In addition several studies completed the program in an attempt to give coherence to the different clinical presentations of this disease, different treatments and interventions for similar clinical phenomena.

Revisión del Programa para la Mejoría Sistemática del Tratamiento del Trastorno Bipolar (STEP-BD) / Revision of systematic treatment enhancement program for bipolar disorder (STEP-BD)

El programa STEP-BD es una iniciativa pública que surge de la necesidad de tener datos sobre el trastorno bipolar obtenidos en entornos de investigación pragmáticos o de la vida real. Los objetivos primarios son: investigar la efectividad de las intervenciones terapéuticas en el trastorno bipolar, el impacto en el curso de la enfermedad de estas intervenciones en entornos pragmáticos o de la vida real y aumentar el conocimiento sobre la enfermedad. Incluyó, en seis años, a 4361 pacientes. Este programa no es un estudio en fases, es una infraestructura compuesta por más de 40 estudios publicados y 30 presentaciones en congresos. Estos estudios tienen por objetivo captar la heterogeneidad de la enfermedad en sus presentaciones clínicas, tratamiento, comorbilidades, funcionalidad y calidad de vida. Los pacientes que ingresan al programa tuvieron una evaluación común. El programa consta de dos ramas principales: tratamiento estándar y tratamientos randomizados de depresión bipolar aguda, depresión bipolar refractaria y prevención de recaídas. Además, diversos estudios completan el programa en un intento de darle coherencia a las diferentes presentaciones clínicas de esta enfermedad, a los diferentes tratamientos y las diferentes intervenciones para fenómenos clínicos similares.(AU)

The STEP-BD is a public initiative, created to generate data, obtained in pragmatic or real life research environments, from the bipolar disorder. The primary objectives are: to investigate the effectiveness of therapeutic interventions in bipolar disorder, the impact on the disease course of these interventions in the "real life" and to raise the knowledge about the disease. This program included in six years, n = 4361 patients. This program is not a study in phases but an infrastructure for more than 40 published studies and 30 conference presentations. These studies aim to capture the heterogeneity of the disease in their different clinical presentations, treatments, comorbidities, functionality and quality of life. Patients entering the program have a common assessment. The program consists of two main pathways: the standard treatment and randomized treatment of acute bipolar depression, bipolar depression and refractory relapse prevention. In addition several studies completed the program in an attempt to give coherence to the different clinical presentations of this disease, different treatments and interventions for similar clinical phenomena.(AU)