Smartphone-Delivered Therapy Improved Negative Symptoms of Schizophrenia Over 16 Weeks

Psychosocial Care for Negative Symptoms Remains Hard to Access

Negative symptoms of schizophrenia include reduced motivation, diminished pleasure, and loss of social interest, along with reduced emotional and verbal expression. In daily life, they can mean losing interest in social activities, finding little enjoyment in everyday experiences, and having less drive to pursue goals and maintain relationships.¹ Guidelines recommend combining medication with evidence-based psychosocial interventions, such as cognitive restructuring of defeatist beliefs, behavioral activation, and social skills training, which aim to rebuild motivation and goal-directed behavior.² These treatments are time-intensive and require specialized clinicians who are not widely available. A digital therapeutic could deliver psychosocial techniques at any time and place.^1,3 Pratap and colleagues tested one such digital option, used alongside antipsychotic treatment, in the phase 3 CONVOKE trial.¹

CT-155 Improved CAINS-MAP Scores More Than Digital Control

The trial explored safety and efficacy of CT-155, a digital therapeutic for negative symptoms of schizophrenia, now FDA-cleared under the brand name Motivista.⁴ This double-blind study (66 US sites) randomized 457 adults receiving antipsychotics 1:1 to CT-155 or a control app with brief educational lessons for 16 weeks. CT-155 combines several evidence-based psychosocial techniques, such as goal setting and behavioral activation. The centrally rated primary endpoint was change in the Clinical Assessment Interview for Negative Symptoms, Motivation and Pleasure subscale (CAINS-MAP), on which higher scores indicate greater severity.^1,3 At week 16, mean scores decreased 6.8 points with CT-155 and 4.2 points with control, a difference of −2.6 (95% CI, −4.0 to −1.2; P < 0.001; Cohen d = −0.36).  Post hoc analyses, unadjusted for multiplicity, favored CT-155 on the Social (−1.44; 95% CI, −2.17 to −0.70) and Recreational (−1.31; 95% CI, −1.97 to −0.65) subdomains but not the Vocational subdomain.¹

Most Stayed Engaged, and No CT-155 Participant Discontinued for Adverse Events

Week 15 retention was somewhat lower with CT-155 (70.4%) than with control (76.5%), although median daily use was higher (6 versus 2 minutes). Treatment-emergent adverse events occurred in 7.9% and 11.7% of CT-155 and control participants, respectively. One event per arm was treatment related. Two control participants and none receiving CT-155 discontinued because of adverse events. Suicidal ideation did not increase in either arm.¹

Durability, Function, and Real-World Use Remain Open Questions

The authors did not report a minimal clinically important difference for the CAINS-MAP, so whether a 2.6-point difference is clinically meaningful remains uncertain.¹ Researchers measured efficacy only through week 16, so the duration of benefit is unknown. Eligibility also required stable antipsychotic dosing, smartphone ownership, and stable housing, while excluding recent psychotherapy.^1,3 These criteria limited variability in symptoms and app use, but they describe a more settled population than is likely seen in routine care. Future studies could examine CT-155 alongside psychotherapy. The trial did not measure functional outcomes and the Vocational subdomain did not separate from control, so whether symptom improvement extends to work, school, and daily functioning is not yet known. Longer follow-up and real-world studies will demonstrate how durable these gains are, if they extend to everyday functioning, and how well they generalize to patients treated in routine care.

References

1. 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.
2. Galderisi S, Kaiser S, Bitter I, et al. EPA guidance on the treatment of negative symptoms in schizophrenia. Eur Psychiatry. 2021;64(1):e21. doi:10.1192/j.eurpsy.2021.13.
3. Lakhan SE, Dorner-Ciossek C, Besedina O, et al. Effectiveness, engagement, and safety of a digital therapeutic (CT-155/BI 3972080) for treating negative symptoms in people with schizophrenia: protocol for the phase 3 CONVOKE randomized controlled trial. JMIR Res Protoc. 2025;14:e81293. doi:10.2196/81293.
4. Click Therapeutics. FDA clears Motivista (CT-155), the first authorized treatment for negative schizophrenia symptoms. News release. October 5, 2026. Accessed October 14, 2026. https://www.biospace.com/press-releases/fda-clears-motivista-ct-155-the-first-authorized-treatment-for-negative-schizophrenia-symptoms.