Smartphone App Improves Motivation and Pleasure in Phase 3 Schizophrenia Trial

In a phase 3 randomized clinical trial published in JAMA Network Open, the investigational digital therapeutic CT-155/BI 3972080 (Boehringer Ingelheim and Click Therapeutics) produced a significantly greater reduction in motivation and pleasure (MAP) negative symptoms than a digital control app. Participants were adults with schizophrenia who were taking antipsychotics.

CT-155 is a smartphone app built on psychosocial strategies such as adaptive goal setting, behavioral activation, and cognitive restructuring of defeatist beliefs. The authors noted that no FDA-approved drug is indicated specifically for negative symptoms. The FDA gave CT-155 Breakthrough Device designation in December 2023.

The double-blind CONVOKE trial (NCT05838625) randomized 457 adults at 66 US sites to CT-155 or a digital control for 16 weeks. All participants were on a stable regimen of up to 2 antipsychotics. The control app delivered educational lessons about the disease. The primary endpoint was the change in score on the MAP subscale of the Clinical Assessment Interview for Negative Symptoms (CAINS-MAP) at week 16. Scores fell by a least-squares mean of 6.8 points with CT-155 and 4.2 points with the control, a difference of −2.6 points (95% CI, −4.0 to −1.2; P < 0.001). The authors described this as a small-to-moderate effect size (Cohen d, −0.36).

In post hoc analyses, the social and recreational subdomains drove most of the improvement. The vocational subdomain did not differ significantly between groups. Expressive negative symptoms and positive symptoms also did not differ between groups at week 16. Serious adverse events occurred in 1.3% of the CT-155 group and 2.2% of the control group, and investigators judged none to be treatment-related. One participant in each group had a treatment-related adverse event: psychotic symptoms with CT-155 and irritability with the control.

The authors said generalizability may be limited because the trial required stable antipsychotic treatment and excluded patients with milder negative symptoms. They added that requiring smartphone ownership, internet access, and stable housing may have introduced selection bias and that real-world studies are needed. Boehringer Ingelheim funded the study, and several authors are employed by the sponsors.

Source: Pratap A, Lakhan SE, Snipes C, et al. A digital therapeutic intervention for negative symptoms of schizophrenia: a randomized clinical trial. JAMA Netw Open. 2026;9(9):e2635753. doi:10.1001/jamanetworkopen.2026.35753