Treatment to Enhance Cognition in Bipolar Disorder (TREC-BD): Efficacy of a Randomized Controlled Trial of Cognitive Remediation Versus Active Control

Objective: Cognitive dysfunction is a core symptom dimension in bipolar disorder and a strong predictor of functional outcomes. Cognitive remediation (CR) produces moderate, durable effects on cognition in patients with schizophrenia; however, studies of CR in patients with bipolar disorder are sparse and findings have been mixed. Thus, the aim of this study was to evaluate the effects of CR versus active control in patients with bipolar disorder with psychosis.

Methods: Patients with a DSM-IV diagnosis of bipolar disorder with psychosis (n = 75) were randomized to a 70-hour computerized CR program or a dose-matched computer control using a parallel design with 1:1 allocation between July 2011 and November 2015. Cognition (primary outcome) and clinical and community functioning (secondary outcomes) were assessed at baseline, at treatment midpoint (after 20-25 hours of training), posttreatment, and at durability (after 6 months of no study contact). Participants and assessment staff were blind to group membership.

Results: 75 participants were randomly assigned to a treatment group, and 72 participants initiated the active phase of treatment and were included in the primary, intent-to-treat analysis (CR: n = 39; Control: n = 33). Linear mixed effects models examining the effects of CR versus Control at posttreatment showed medium to large effects of CR on processing speed (d = 0.42), visual learning and memory (d = 0.92), and the composite (d = 0.80). Superiority of CR over Control on processing speed (d = 0.65) and composite (d = 0.83) was maintained or increased at durability. CR was not associated with change in community functioning, although cognitive change was associated with functional change across the sample.

Conclusions: Cognitive remediation produced significant improvements over an active control in several cognitive domains and the cognitive composite. While both groups improved on several domains relative to baseline, durability of gains was unique to CR.

Trial Registration: ClinicalTrials.gov identifier: NCT01470781