Digital Therapy CT-155 Shows Promise for Negative Symptoms of Schizophrenia in Randomized Trial

A digital therapeutic designed to target some of the most stubborn and disabling features of schizophrenia has delivered encouraging results in a randomized clinical trial, according to findings published in JAMA Network Open. The intervention, known as CT-155, improved what clinicians call motivation and pleasure negative symptoms, with an effect size described as small to moderate and comparable to what is typically achieved with established psychosocial interventions and pharmacologic treatments in psychiatry. The trial also found the therapy to be well tolerated and safe, positioning it as a potential novel adjunctive option for people living with schizophrenia.

Negative symptoms represent one of the most challenging dimensions of schizophrenia. Unlike positive symptoms such as hallucinations and delusions, which involve the presence of abnormal experiences, negative symptoms involve the absence or diminution of normal functioning. These include avolition, or a reduced drive to initiate and sustain goal-directed activity, anhedonia, or a diminished capacity to experience pleasure, asociality, blunted affect, and poverty of speech. For many patients, these symptoms persist even when antipsychotic medications successfully control hallucinations and delusions, and they are strongly linked to social isolation, unemployment, and reduced quality of life.

The scarcity of effective treatments for negative symptoms has long frustrated clinicians and researchers. Most antipsychotic drugs, which primarily act on dopamine systems to suppress positive symptoms, offer little benefit for motivational and pleasure deficits. Psychosocial approaches such as cognitive behavioral therapy and social skills training can help, but their effects are often modest, and access to trained therapists remains a barrier in many health systems. This treatment gap has made the development of scalable, evidence-based interventions for negative symptoms a major priority in mental health research.

CT-155 was developed as a digital therapeutic, a class of software-based interventions intended to deliver therapeutic benefit through structured engagement, often on a computer or tablet. Digital therapeutics differ from general wellness apps in that they are designed to be evaluated in clinical trials with the same rigor expected of medical treatments, measuring safety and efficacy against defined endpoints. In this trial, the intervention was tested specifically against motivation and pleasure negative symptoms, the domain that most directly shapes a patient’s ability to pursue goals, enjoy daily activities, and maintain social connections.

The randomized clinical trial design is the gold standard for determining whether an intervention produces genuine benefit beyond placebo effects or the natural course of a condition. By randomly assigning participants to receive either the digital therapeutic or a comparator, researchers can isolate the specific contribution of the active intervention. In this study, the trial demonstrated that CT-155 improved motivation and pleasure negative symptoms to a degree the investigators characterized as small to moderate. While such effect sizes may sound modest, in psychiatry they are consistent with the magnitude of benefit typically observed for approved psychosocial interventions and pharmacologic treatments, which underscores the clinical relevance of the finding.

Safety and tolerability are equally critical considerations for any new schizophrenia treatment, particularly because patients often take multiple medications and may be sensitive to side effects. The trial reported that CT-155 was well tolerated and safe, an outcome that is notable for a software-based intervention that does not add pharmacologic burden. Because the therapy works through structured digital engagement rather than drug action on brain chemistry, it can in principle be combined with existing antipsychotic regimens without concerns about drug-drug interactions, supporting its proposed role as an adjunctive therapy rather than a replacement for medication.

The corresponding author of the study is Abhishek Pratap, PhD, of Global Clinical Development Mental Health and Eye Health at Boehringer Ingelheim Pharmaceuticals Inc, indicating that the intervention emerged from an industrial research and development program focused on mental health. The involvement of a major pharmaceutical company reflects a broader trend in which drug developers are expanding into digital and combination approaches, recognizing that software-delivered interventions can address aspects of psychiatric illness that molecules alone have failed to reach.

Perhaps the most consequential implication of the finding is scalability. Traditional psychosocial interventions for schizophrenia require trained clinicians, scheduled sessions, and institutional infrastructure, all of which limit how many patients can be reached. A digital therapeutic, once validated and deployed, can in principle be distributed widely and used with far fewer constraints on clinician time and geography. The authors suggest that CT-155 may represent a scalable, accessible option for improving schizophrenia negative symptoms, a claim that carries significant weight for health systems struggling to meet the demand for mental health care.

At the same time, the small-to-moderate effect size is a reminder that digital therapeutics are not a cure and that real-world performance can differ from trial conditions. Questions about long-term durability of benefit, adherence over months and years of use, and effectiveness across diverse patient populations will shape how such interventions are ultimately integrated into care. Digital interventions also depend on patients engaging with the software, and motivation is precisely the faculty impaired by negative symptoms, a challenge that the design of the therapy must address for sustained benefit.

Nevertheless, the trial marks a meaningful step forward in a field where genuine treatment advances for negative symptoms have been rare. Published in JAMA Network Open, a peer-reviewed journal, the study adds to a growing body of evidence that carefully engineered digital interventions can produce clinically measurable improvements in serious mental illness. For the millions of people worldwide living with schizophrenia, many of whom face persistent motivational and pleasure deficits that medications do not relieve, a safe, well-tolerated, and scalable adjunctive therapy offers a reason for cautious optimism and a signal of where psychiatric treatment may be heading.

Subject of Research: A randomized clinical trial of the digital therapeutic CT-155 for negative symptoms of schizophrenia

Article Title: A digital therapeutic intervention for negative symptoms of schizophrenia

Article References: A digital therapeutic intervention for negative symptoms of schizophrenia. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: schizophrenia, negative symptoms, digital therapeutics, CT-155, randomized clinical trial, JAMA Network Open, motivation and pleasure deficits, psychiatry, mental health, Boehringer Ingelheim, adjunctive therapy, avolition