Breakthrough Clinical Results
Boehringer Ingelheim and Click Therapeutics announced positive results from the Phase III CONVOKE study of CT-155, an investigational prescription digital therapeutic, as an adjunct to standard antipsychotic therapy for experiential negative symptoms of schizophrenia. The study met its primary endpoint, demonstrating a statistically significant reduction in negative symptoms as measured by the CAINS-MAP scale. CT-155 was well-tolerated, and the companies plan to advance discussions with regulators. The design and development of CT-155 was informed by an iterative patient-centered approach with more than 150 people living with schizophrenia.
Key Highlights
- CT-155 showed a statistically significant reduction in experiential negative symptoms of schizophrenia in a Phase III trial.
- The CONVOKE study met its primary endpoint, with CT-155 demonstrating a 6.8-point improvement in negative symptoms severity as measured by CAINS-MAP at 16 weeks.
- CT-155 was well-tolerated with an adverse event profile consistent with past studies.
- CT-155 integrates psychosocial interventions delivered using an adaptive goal-setting technique.
Incidence and Prevalence
Global Estimates of Schizophrenia Incidence and Prevalence
According to the Global Burden of Disease study 2019, the global prevalence of schizophrenia was estimated at 23.60 million cases (95% uncertainty interval: 20.23-27.15). Four countries - China, India, the USA and Indonesia - accounted for 50.72% of this global prevalence.
The global prevalence has increased slightly from 1990 to 2019, with an annual percentage change of 0.03% (95% confidence interval 0.01-0.05). This increase has not been uniform across regions, with intermediate sociodemographic index regions accounting for a greater proportion of prevalence increase compared to high-index regions.
Regarding incidence rates, systematic reviews covering studies from 1980-2000 found a 1-year incidence of 11.1 per 100,000 population. Another source indicates the annual incidence averages 15 per 100,000. A community survey reported an annual prevalence of 5.7 and an incidence of 3, though units were not specified.
The lifetime prevalence of schizophrenia is approximately 1% worldwide, making it a major public health problem internationally. The systematic review mentioned earlier found a pooled rate of 0.55 per 100 for lifetime prevalence and 0.34 per 100 for 1-year prevalence. The point prevalence averages approximately 4.5 per 1000 population, while the lifetime risk of developing schizophrenia averages 0.7%.
Age patterns show that prevalence is highest among individuals 30-59 years old across all sociodemographic regions. Interestingly, prevalence decreased among those born after 1979 in regions with intermediate sociodemographic index, while it consistently improved among all birth cohorts in regions with low index.
There is significant variation in schizophrenia rates globally, with studies showing 2- to 5-fold differences between populations. Urbanicity, male gender, and migration history are associated with higher risk of developing schizophrenia. This heterogeneity supports the hypothesis that there is real variation in the distribution of schizophrenia worldwide.
The burden of disease is heavier in less affluent regions and disproportionately affects working-age individuals (30-59 years) globally. For regions with lower sociodemographic indices, the increasing burden among recent birth cohorts is more pronounced.
Cross-cultural studies, particularly WHO research projects (IPSS and DOSMED), indicate that the course and outcome of schizophrenia are better in patients from developing countries, though the reasons remain speculative. It is likely that prognosis varies according to economic development rather than culture specifically.
In Kazakhstan, for example, 45,054 individuals receive medical treatment for schizophrenia, indicating a prevalence rate of 238.6 per 100,000 people, which is lower than the global average of approximately 1%.
Key Unmet Needs and Target Populations in Schizophrenia Treatment
Major Unmet Treatment Needs
Cognitive symptoms represent a significant unmet need in schizophrenia treatment, with 75% of psychiatrists and 45% of PCPs acknowledging their presence. Despite 89% of psychiatrists and 88% of PCPs considering detection of these symptoms crucial for improving patient functionality, over half of both groups do not consistently evaluate cognitive symptoms due to time constraints, limited treatment access, and lack of effective diagnostic tools.
Treatment-resistant schizophrenia (TRS) affects approximately 30%-50% of people with schizophrenia in the European Union. These patients do not experience sustained symptom relief, have the most severe disease-related disability, and generate the highest associated costs among individuals with severe mental disorders.
Persistent positive symptoms in TRS patients cause significant perceived burden on caregivers, feelings of being overwhelmed, and substantial negative impacts on caregivers' emotional and physical health.
Negative symptoms remain inadequately addressed by current antipsychotic medications, with many patients experiencing debilitating residual symptoms despite treatment.
Emerging Treatment Approaches
Non-pharmacological interventions are emerging as important treatment options: - Evidence-based psychosocial interventions (EBPIs) - Non-Invasive Brain Stimulation (NIBS) targeting negative and cognitive symptoms - Repetitive transcranial magnetic stimulation (rTMS) showing promise for negative symptoms and cognitive function
Novel pharmacological treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic pathways, and glutamate modulation have emerged as promising alternatives to address unmet needs.
Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some symptoms.
Target Populations
Treatment-refractory patients are being targeted with antipsychotic polypharmacy, specifically combination therapy with olanzapine plus risperidone.
Patients with varying baseline symptom severity are being studied, with findings showing antipsychotic drugs benefit the full spectrum of patients with acute schizophrenia.
Both female and male patients with chronic schizophrenia are being targeted with selective estrogen receptor modulators (SERMs), particularly raloxifene, as an augmentation strategy.
Patients with tardive dyskinesia (TD) are being considered for alternative management strategies beyond antipsychotic dose reduction.
Patients with early-phase psychosis or clinical high-risk of psychosis (CHR) are targeted for preventive interventions, particularly in low- and middle-income countries.
Patients requiring personalized treatment approaches are being targeted with artificial intelligence (AI) models to predict treatment response.
Patients with physical health needs are being targeted for integrated care involving co-location of physical and mental health services.
Patients at end-of-life with reduced access to hospice facilities are being identified as needing improved palliative care access.
Black patients face racial disparities in diagnosis and treatment, being overrepresented in schizophrenia diagnoses and having nearly twice the odds of receiving a schizophrenia diagnosis compared to White patients.
Recent Studies
Recent Schizophrenia Studies: Interventions, Safety, and Efficacy
Family-Based Interventions (2024 Cochrane Review)
This review examined 26 RCTs with 1985 people with schizophrenia. Efficacy outcomes showed family interventions may reduce patient relapse (RR 0.66), reduce caregiver burden, and result in more family members shifting from high to low expressed emotion. For safety, there was little to no difference in patient death and hospital admission compared to standard care. Evidence quality was moderate to very low certainty.
Computerised Interactive Remediation of Cognition and Thinking Skills (CIRCuiTS) (2024)
This study included 30 adults with schizophrenia and psychotic spectrum disorders. Efficacy outcomes showed participants' mean adaptive functioning increased from the extremely low range to the low range with large effect sizes (Cohen's d = 0.92-1.24). Significant improvements were seen in communication and functional academics.
Online Treatments for Families (2021 Systematic Review)
This review identified 9 viable studies. Efficacy outcomes showed online interventions were well accepted with good adherence and satisfaction. Family outcomes included improved burden and decreased stress. Patient outcomes showed decreased severity of positive symptoms and fewer hospitalizations.
Levetiracetam for Schizophrenia (2022 RCT)
This three-blind randomized clinical trial included 40 chronic schizophrenic patients. Efficacy outcomes showed levetiracetam had significant effects on clinical symptoms, especially negative symptoms, and significant impact on cognitive functions.
Xanomeline-trospium (KarXT) (2025)
This novel pharmacological treatment targeting muscarinic receptors demonstrated significant improvements with a mean reduction of 17.4 points in PANSS and CGI-S scores. Safety outcomes showed adverse events were mostly mild and transient, with nausea, constipation, and somnolence being common.
Brexpiprazole in Adolescents (2025)
In this study, 56.9% of patients reported treatment-emergent adverse events (TEAEs), most commonly somnolence (10.2%), headache (9.0%), weight increase (9.0%), and nasopharyngitis (6.6%). Most TEAEs were mild or moderate. Clinically meaningful weight gain occurred in 19.8% of patients. Only 1.2% discontinued due to adverse events.
Specialized Early Intervention (SEI) Teams (2020 Cochrane Review)
This review included three RCTs with 780 participants. Efficacy outcomes showed extended SEI may result in fewer disengagements from mental health treatment (15%) compared to standard SEI + TAU (34%). Evidence regarding lower global psychotic symptoms was uncertain, with low or very low certainty.
Electroconvulsive Therapy (ECT) in Adolescents
ECT showed significant improvement in BPRS, MADRS, and CGI-S scores in adolescents, with 48.5% of patients showing significant clinical improvement.
Transcranial Magnetic Stimulation (TMS)
Temporoparietal TMS showed improvement in global state (CGI scale) and positive symptoms (PANSS scale), while prefrontal theta burst stimulation TMS improved mental state on the PANNS scale.