Background Classic and second generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the “real-world” advantages and disadvantages of these medications Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This paper outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments. The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool. Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus adjunctive personalized treatment (APT), across ten sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. 482 participants were randomized to the study and 364 completed. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants’ ability to pay for study medications. Conclusion We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a second generation antipsychotic with broad-spectrum activity in bipolar disorder and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial.

ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

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Standardized lexical analysis of verbal output has not been applied to verbal fluency tasks in schizophrenia. Performance of individuals with schizophrenia on both a letter (n=139) and semantic (n=137) fluency task was investigated. The lexical characteristics (word frequency, age-of-acquisition, word length, and semantic typicality) of words produced were evaluated and compared to those produced by a healthy control group matched on age, gender, and WAIS-III vocabulary scores (n=20). Overall, individuals with schizophrenia produced fewer words than healthy controls, replicating past research (see Bokat and Goldberg, 2003). Words produced in the semantic fluency task by individuals with schizophrenia were, on average, earlier acquired and more typical of the category. In contrast, no differences in lexical characteristics emerged in the letter fluency task. The results are informative regarding how individuals with schizophrenia access their mental lexicons during the verbal fluency task.

The 7- and 12-item CHRT-SR both had excellent psychometric properties in a sample of symptomatic subjects with bipolar disorder. The scale is highly correlated with depression, functioning, and quality of life, but not with mania. Future research is needed to determine whether the CHRT-SR will be able to predict suicide attempts in clinical practice.