Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force

Abstract

ObjectivesTo aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus‐based guidance paper for the methodology and design of cognition trials in bipolar disorder.MethodsThe task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face‐to‐face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.ResultsKey methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non‐study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.ConclusionsThis ISBD task force guidance paper provides the first consensus‐based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.

Executive functions and memory in bipolar disorders I and II: new insights from meta‐analytic results

“…The comprehensiveness issue stems from the fact that several observational studies do not use euthymia as an inclusion criterion, or choose to admit patients with subsyndromal mood symptoms. The inclusion of these patients in clinical trials has actually been recommended in some cases, in the interest of recruitment feasibility and generalization of results (71). As such, since one aim of this study was precisely to provide a more comprehensive review of the literature than has been previously attempted, it was important to include studies which evaluated non-euthymic as well as euthymic samples.…”

Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: An overview of evidence

“…It is now widely recognized that a substantial proportion of individuals with bipolar disorder (BD) experience cognitive impairments that persist even beyond the resolution of mood symptoms . Although it is becoming increasingly clear that these impairments adversely impact psychosocial functioning, key questions remain regarding their cause, trajectory and correlates.…”

“…It is now widely recognized that a substantial proportion of individuals with bipolar disorder (BD) experience cognitive impairments that persist even beyond the resolution of mood symptoms. 1,2 Although it is becoming increasingly clear that these impairments adversely impact psychosocial functioning, key questions remain regarding their cause, trajectory and correlates. A better understanding of the factors associated with impairments in cognition is critically needed to progress the development of intervention strategies directly targeted at remediating cognitive dysfunction and preventing subsequent cognitive decline in the illness.…”

Thinking about cognitive impairment in bipolar disorder: A clinical perspective

“…Interest in the cognitive impairment seen in euthymic bipolar individuals has exploded over the last few years as evidenced by the number of papers on this topic published in Bipolar Disorders, and by the two recent International Society for Bipolar Disorders (ISBD) task force papers on clinical evaluation and treatment and clinical trial design of cognitive impairment . This increased interest and attention is both welcome, and, frankly, delayed.…”

“…Interest in the cognitive impairment seen in euthymic bipolar individuals has exploded over the last few years as evidenced by the number of papers on this topic published in Bipolar Disorders, and by the two recent International Society for Bipolar Disorders (ISBD) task force papers on clinical evaluation and treatment and clinical trial design of cognitive impairment. 1,2 This increased interest and attention is both welcome, and, frankly, delayed. Our colleagues studying schizophrenia have been focusing on this area of research for many years, assuredly due to the greater overall impairment in schizophrenia and the consistent evidence that cognitive impairment explains a substantial proportion of the functional impairment of schizophrenic individuals.…”