A Smartphone-Based Intervention as an Adjunct to Standard-of-Care Treatment for Schizophrenia: Randomized Controlled Trial

BACKGROUND: Antipsychotic medications have limited benefits in schizophrenia, and cognitive behavioral therapy may be beneficial as an adjunct. There may be potential for implementing mobile cognitive behavioral therapy–based treatment for schizophrenia in addition to standard antipsychotic medications. OBJECTIVE: This study aims to determine whether PEAR-004, a smartphone-based investigational digital therapeutic, improves the symptoms of an acute psychotic exacerbation of schizophrenia when it is added to standard treatments. METHODS: This was a 12-week, multicenter, randomized, sham-controlled, rater-blinded, parallel group proof‑of‑concept study of 112 participants with moderate acute psychotic exacerbation in schizophrenia. This study was conducted in 6 clinical trial research sites in the United States from December 2018 to September 2019. The primary outcome, change in Positive and Negative Syndrome Scale (PANSS) from baseline to week 12 or the last available visit, was analyzed using the mixed-effects regression model for repeated measures, applied to an intent-to-treat sample. RESULTS: The total PANSS scores slightly decreased from baseline over the study period in both groups; the treatment difference at day 85 between PEAR-004 and sham was 2.7 points, in favor of the sham (2-sided P=.09). The secondary scales found no benefit, except for transient improvement in depressive symptoms with PEAR-004. Application engagement was good, and patient and clinical investigator satisfaction was high. No safety concerns were observed. There was some evidence of study site heterogeneity for the onboarding processes and directions on PEAR-004 product use at baseline and throughout the study. However, these differences did not affect the efficacy results. CONCLUSIONS: In the largest-to-date randomized, sham-controlled study of a digital therapeutic in schizophrenia, PEAR-004 did not demonstrate an effect on the primary outcome—total PANSS scores—when compared with a nonspecific digital sham control. The secondary and exploratory results also did not demonstrate any notable benefits, except for possible temporary improvement in depressive symptoms. This study provided many useful scientific and operational insights that can be used in the further clinical development of PEAR-004 and other investigational digital therapeutics. TRIAL REGISTRATION: ClinicalTrials.gov NCT03751280; https://clinicaltrials.gov/ct2/show/NCT03751280