Jodi M. Gonzalez

Development of the Bipolar Inventory of Symptoms Scale

Objective:  Most rating scales for bipolar disorders (BDs) do not encompass the spectrum of symptomatology now established as characterizing the illness. We report the rationale, format, reliability and initial validity studies of the Bipolar Inventory of Symptoms Scale (BISS), a 44‐item scale designed to encompass the spectrum of behavioral disturbances in BDs.

Ethnicity/race and outcome in the treatment of depression: results from STAR*D.

Objectives:This secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared rates of remission and response for blacks (n = 495), whites (n = 1853), and Hispanics (n = 327) with nonpsychotic major depressive disorder who were treated with citalopram. Methods:STAR*D included representative outpatients treated in 23 psychiatric and 18 primary care centers. Participants received flexible doses of citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission, using a measurement-based care approach with adjustments based on symptoms and side effects assessed at each visit. Results:There were significant differences among groups on many baseline demographic, sociocultural, and clinical variables. Blacks and Hispanics were more socially disadvantaged and had more comorbidity than whites. Before adjusting for differences, blacks had lower remission rates than whites, with Hispanics intermediate between the 2. After adjustments, remission rates for groups were not significantly different on the 17-item Hamilton Rating Scale for Depression (HRSD), but remained lower for blacks compared with whites with the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR). Blacks took longer to achieve remission or response, though this did not remain after adjusting for baseline differences. Conclusions:Overall, black and to a lesser extent Hispanic participants had a poorer response to citalopram. After adjusting for baseline differences, the remission rates seemed to be more similar on the HRSD, but remained worse for blacks on the QIDS-SR. We discuss the possible biologic and sociocultural factors that may underlie these findings.

Medical Comorbidity Among Youth Diagnosed With Bipolar Disorder in the United States

OBJECTIVE This study examines the number and type of medical comorbidities among youth diagnosed with bipolar disorder. METHOD This is a retrospective data analysis using the 2000-2001 Thomson Medstat MarketScan medical claims and administrative files. The population included a national sample of youth (ages 6-18 years) from privately insured families within the United States. Number of chronic medical conditions and type of medical comorbidity were analyzed in ICD-10-diagnosed youth with bipolar disorder (N = 832) and other types of psychiatric disorders (N = 21,493) using The Johns Hopkins Adjusted Clinical Groups Case Mix System, Version 8.0. RESULTS Thirty-six percent of youth with bipolar disorder had 2 or more chronic health conditions versus 8% of youth with other psychiatric diagnoses. The following categories of medical conditions were significantly more prevalent in youth diagnosed with bipolar disorder: cardiology, gastrointestinal/hepatic, neurologic, musculoskeletal, female reproductive, and respiratory. Toxic effects and adverse events were also higher in youth with bipolar disorder, compared to youth with other psychiatric disorders. CONCLUSIONS Youth with bipolar disorder experience higher rates of several medical illnesses compared to youth with other psychiatric diagnoses. Several factors may explain this phenomenon, including worse medication side effects, unhealthy lifestyle behaviors, poorer access to health care services, socioeconomic status, and biologic susceptibility. Moreover, a diagnosis of bipolar disorder may reflect more frequent health care utilization and therefore more opportunities for additional medical diagnoses. Further understanding regarding reasons for these relatively high rates of comorbidity among youth diagnosed with bipolar disorder may be helpful in improving overall health and quality of life during the early stages/onset of this disorder.

Principal domains of behavioral psychopathology identified by the Bipolar Inventory of Signs and Symptoms Scale (BISS)

Current symptom rating scales and diagnostic categories for bipolar disorder (BD) do not provide dimensional profiles of the types of behavior disturbed in this complex disorder. To overcome these limitations we identified the principal domains of behavioral symptomatology in bipolar individuals, including all mood states, and used a more comprehensive rating scale for BD: the Bipolar Inventory of Signs and Symptoms Scale (BISS). A total of 246 patients with BD (196 with BD type I, and 50 with BD type II) were interviewed using the BISS. Exploratory factor analysis was performed on the BISS results using the maximum likelihood factor extraction method, followed by oblique rotation of the extracted factor loadings. We determined the strength of relationships between factor scores using the Pearson correlation coefficient. The following five factors were extracted: mania, depression, irritability, anxiety and psychosis. Anxiety was significantly correlated with depression and irritability. The mania factor score was only weakly associated with the other four factors. The domains of the BISS capture both the historical categories of depression and mania, plus irritability, psychosis, and an additional principal domain, anxiety. Despite the common occurrence of anxiety in BD, it has not been identified in most prior factor analyses, in part due to limited coverage of anxiety symptoms in the source scales.

Development of the Bipolar Inventory of Symptoms Scale: concurrent validity, discriminant validity and retest reliability

Scales used in studies of bipolar disorder have generally been standardized with major depressive or hospitalized manic patients. A clinician rated scale based on a semi‐structured interview for persons with bipolar disorder, with comprehensive coverage of bipolar symptomatology, is needed. We report concurrent, divergent and convergent psychometric reliability, discriminant validity and relationship to a measure of overall function for a new psychometric rating instrument. A primarily outpatient sample of 224 subjects was assessed using the Bipolar Inventory of Symptoms Scale (BISS). The BISS total score and depression and mania subscales were compared to the Young Mania Rating Scale (YMRS), the Montgomery Asberg Depression Rating Scale (MADRS) and the Global Assessment of Functioning Scale (GAF). Clinical mood states were also compared using the BISS. The BISS scores demonstrated good concurrent validity, with estimates (Pearson correlations) ranging from 0.74 to 0.94 for YMRS and MADRS and test–retest reliability from 0.95 to 0.98. BISS concurrent validity with the GAF was significant for four clinical states, but not mixed states. The BISS discriminated primary bipolar mood states as well as subjects recovered for eight weeks compared to healthy controls. In conclusion, the BISS is a reliable and valid instrument broadly applicable in clinical research to assess the comprehensive domains of bipolar disorder. Future directions include factor analysis and sensitivity to change from treatment studies. Copyright

Aims and Results of the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP‐BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP‐BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP‐BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP‐BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders.

Review of the safety, efficacy, and side effect profile of asenapine in the treatment of bipolar 1 disorder

Objective: Asenapine is approved for acute manic and mixed states in bipolar disorder. The objective is to review the efficacy of asenapine in bipolar disorder, with a particular focus on acceptability and adherence to treatment. Methods: Five clinical trials were conducted in bipolar disorder manic or mixed states: two 3-week trials (n = 976) comparing asenapine to placebo, a 9-week extension (n = 504), and a 40-week extension (n = 107). One trial was conducted comparing asenapine to placebo (n = 326) as adjunctive therapy for subjects with an incomplete response to lithium or valproate. All trials were conducted in the USA and internationally. Results: Asenapine was found to be efficacious for manic and mixed states in bipolar disorder compared with placebo control, and compares equally well to olanzapine on efficacy measures after 3 weeks of treatment. Asenapine was not found to be efficacious for depression symptoms. Common asenapine side effects in the 40-week extension trial were sedation, insomnia, and dizziness, and 31% reported clinically significant weight gain, compared with 55% reporting clinically significant weight gain with olanzapine. Additionally, 18% had clinically significant changes in fasting blood glucose levels compared to 22% of those on olanzapine. In terms of patient acceptability, one concern may be sublingual administration requiring no liquids or food for 10 minutes after dosing and a twice-daily regimen. Suggestions about addressing barriers to adherence and acceptability are provided. Conclusion: Asenapine is a promising new medication in bipolar disorder. Asenapine in the long-term has a more favorable weight gain profile compared to olanzapine. No benefit was seen for depression symptoms, a major patient-reported concern. Some side effects do not remit after the short-term trials in at least 10% of patients.

Caregiver burden as a predictor of depression among family and friends who provide care for persons with bipolar disorder

Over one‐third of caregivers of people with bipolar disorder report clinically significant levels of depressive symptoms. This study examined the causal relationship between depression and caregiver burden in a large sample of caregivers of adult patients with bipolar disorder.

A qualitative assessment of cross-cultural adaptation of intermediate measures for schizophrenia in multisite international studies.

In this substudy of the Measurement and Treatment Research to Improve Cognition in Schizophrenia we examined qualitative feedback on the cross-cultural adaptability of four intermediate measures of functional outcome (Independent Living Scales, UCSD Performance-Based Skills Assessment, Test of Adaptive Behavior in Schizophrenia, and Cognitive Assessment Interview). Feedback was provided by experienced English-fluent clinical researchers at 31 sites in eight countries familiar with medication trials. Researchers provided feedback on test subscales and items which were rated as having adaptation challenges. They noted the specific concern and made suggestions for adaptation to their culture. We analyzed the qualitative data using a modified Grounded Theory approach guided by the International Testing Commission Guidelines model for test adaptation. For each measure except the Cognitive Assessment Interview (CAI), the majority of subscales were reported to require major adaptations in terms of content and concepts contained in the subscale. In particular, social, financial, transportation and health care systems varied widely across countries-systems which are often used to assess performance capacity in the U.S. We provide suggestions for how to address future international test development and adaptation.

Discriminating primary clinical states in bipolar disorder with a comprehensive symptom scale.

Objective:  We assessed the spectrum and severity of bipolar symptoms that differentiated bipolar disorder (BD) clinical states, employing the Bipolar Inventory of Symptoms Scale (BISS) which provides a broader item range of traditional depression and mania rating scales. We addressed symptoms differentiating mixed states from depression or mania/hypomania.