Efficacy of Acceptance and Commitment Therapy in Daily Life (Act-Dl) in Early Psychosis: Results from the Multi-Centre Interact Randomized Controlled Trial

Background: Treatment in the early stages of psychosis is crucial to prevent poor clinical and social outcomes. The aim of this study was to investigate the efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in reducing psychotic distress in a multi-centre randomised controlled trial of individuals with an Ultra-high Risk for Psychosis (UHR) or a first-episode of psychosis (FEP).  Methods: Individuals aged 15-65 years with a clinically established UHR or FEP status were recruited from secondary mental health services in 5 regions and were randomly assigned to treatment as usual (TAU) or ACT-DL+TAU. ACT-DL consisted of 8 ACT sessions augmented with an EMI app. The primary outcome was a reduction in psychotic distress as assessed with CAARMS at post-intervention, 6- and 12-month follow-up. Secondary outcomes were symptom severity, functioning and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. Findings: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomised to ACT-DL+TAU (n=71) or TAU (n=77). 115 (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of a greater reduction in CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3)=2·38; p=0·50). However, momentary psychotic distress (χ2(3)=21·56; p<0·001) and negative symptom severity (χ2(3)=15·96; p=0·001) was reduced and global functioning improved (χ2(3)=8·72; p=0·033) in ACT-DL+TAU compared to TAU. No serious adverse events directly related to the therapy occurred.  Interpretation: Although the trial did not support a significant effect on psychotic distress as assessed with the CAARMS, significant improvements were found for momentary psychotic distress, global functioning and negative symptomatology. These results are promising given that these latter problems are among the hardest to treat. Clinical Trial Registration Details: The trial was prospectively registered in the Netherlands Trial Register (NTR4252).  Funding Information: This work was supported by an ERC Consolidator Grant (ERC-2012-StG, project 309767—INTERACT) to IMG as well as an NWO VENI Grant (no. 451– 13-022) and DFG Heisenberg professorship (no. 389624707) to UR. Declaration of Interests: The study received ethical approval from the MERC at Maastricht University Medical Centre (MUMC), the Netherlands (reference: NL46439.068.13) and the University Clinic Leuven, Belgium (reference: B322201629214). Ethics Approval Statement: A week after being fully informed by a researcher, informed consent was obtained.