Cognitive Remediation Therapy for Patients with Bipolar Disorder: A Randomised Proof-of-Concept Trial

Abstract

Background: Cognitive remediation therapy (CRT) may benefit people with bipolar disorders but randomised trials of evidenced therapy programmes for those with bipolar type I and II are lacking. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. Methods: This proof-of-concept, single-blind randomised trial recruited participants from the community, primary and secondary care to one centre in London, UK. Participants were aged 18-65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment-as-usual (TAU) with or without individual CRT for 12 weeks. The partly-computerised CRT programme (CIRCuiTS) was therapist-led and evidence-based. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention-to-treat analyses. Trial registration: ISRCTN ID32290525. Findings: 60 participants were recruited (02/2016-06/2018) and randomised to CRT (n=29) or TAU (n=31). Trial withdrawals were equivalent (CRT n=2/29; TAU n=5/31). CRT satisfaction indicated high acceptability. Intention-to-treat analyses (N=60) demonstrated greater improvements for CRT- than TAU-randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in IQ (SES=0·71, 95% CI [0·29,1·13]), working memory (SES=0·70, 95% CI [0·31,1·10]), executive function (SES=0·93, 95% CI [0·33,1·54]), psychosocial functioning (SES=0·49, 95% CI [0·18,0·80]) and goal attainment (SES=2·02, 95% CI [0·89,3·14]). No serious adverse events were reported. Interpretation: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof-of-concept trial encourages further investigation in a definitive trial. Trial Registration Number: ISRCTN ID32290525. Funding: National Institute for Health Research (NIHR) Research for Patient Benefit Programme (PB-PG-0614-34075) and NIHR Maudsley Biomedical Research Centre. Declaration of Interest: TW and CR were involved with the CIRCuiTs programme development; however, neither author had any involvement with undertaking or supervising any assessment procedures or data analysis, or data collection. AHY has received payment for lectures and advisory boards membership from AstraZenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, and Janssen and reports no shareholdings in pharmaceutical companies. He is the lead investigator for the Embolden Study (AZ), BCI Neuroplasticity Sudy, and Aripiprazole Mania Study, and has led investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, and Janssen. RS has received an honorarium for speaking at a Lundbeck-sponsored event. The remaining authors declare no competing interests (DT, JH, TM, NY, PM, JB, KM, MC, JF). Ethical Approval: The trial protocol contains full details of the study methodology as approved by a UK NHS Research Ethics Committee (16/10/2015, reference 15/LO/1557).