title: Assessing cognitive function in bipolar disorder: challenges and recommendations for clinical trial design.
abstract: OBJECTIVE
  Neurocognitive impairment in schizophrenia has been recognized for more than a century. In contrast, only recently have significant neurocognitive deficits been recognized in bipolar disorder. Converging data suggest the importance of cognitive problems in relation to quality of life in bipolar disorder, highlighting the need for treatment and prevention efforts targeting cognition in bipolar patients. Future treatment trials targeting cognitive deficits will be met with methodological challenges due to the inherent complexity and heterogeneity of the disorder, including significant diagnostic comorbidities, the episodic nature of the illness, frequent use of polypharmacy, cognitive heterogeneity, and a lack of consensus regarding measurement of cognition and outcome in bipolar patients. Guidelines for use in designing future trials are needed.
  
  
  METHODS
  The members of the consensus panel (each of the bylined authors) were selected based upon their expertise in bipolar disorder. Dr Burdick is a neuropsychologist who has studied cognition in this illness for 15 years; Drs Ketter, Calabrese, and Goldberg each bring considerable expertise in the treatment of bipolar disorder, both within and outside of controlled clinical trials. This consensus statement was derived from work together at scientific meetings (eg, symposium presentation at the 2014 Annual Meeting of the American Society of Clinical Psychopharmacology, among others) and ongoing discussions by conference call. With the exception of the public presentations on this topic, these meetings were closed to outside participants.
  
  
  METHODS
  A literature review was undertaken by the authors to identify illness-specific challenges relevant to the design and conduct of treatment trials targeting neurocognition in bipolar disorder. Expert opinion from each of the authors guided the consensus recommendations.
  
  
  METHODS
  Consensus recommendations, reached by unanimous opinion of the authors, are provided here as a preliminary guide for future trial design. Recommendations comprise exclusion of certain syndromal-level comorbid diagnoses and current affective instability, restrictions on numbers and types of medications, and use of prescreening assessment to ensure enrollment of subjects with adequate objective evidence of baseline cognitive impairment.
  
  
  CONCLUSIONS
  Clinical trials to address cognitive deficits in bipolar disorder face distinctive design challenges. As such trials move from proof-of-concept to confirmation of clinical efficacy, it will be important to incorporate distinctive design modifications to adequately address these challenges and increase the likelihood of demonstrating cognitive remediation effects. The field is now primed to address these challenges, and a comprehensive effort to formalize best practice guidelines will be a critically important next step.
authors.affiliation: One Gustave L. Levy Pl, Box 1230, New York, NY 10029 Katherine.burdick@mssm.edu.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burdick
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Goldberg
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D001714:Bipolar Disorder / Q000150:complications*; D002986:Clinical Trials as Topic / Q000592:standards*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D032921:Consensus; D017408:Guidelines as Topic; D006801:Humans; D012107:Research Design / Q000592:standards*
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