SMI Research Digest: Treatment for Comorbid Substance Use
SMI Research Digest is a monthly publication from Treatment Advocacy Center (TAC) that summarizes recently published research on topics related to severe mental illness (SMI). This month, we feature three articles about treatment for comorbid substance use disorders among people with schizophrenia. While many people with schizophrenia have comorbid substance use disorders, people with dual diagnoses have often been excluded from research and rarely receive treatment for both disorders, making this an important area of focus for future research into and treatment of schizophrenia.
Approximately 9 out of 10 people with schizophrenia and a comorbid substance use disorder receive no substance use treatment. The Mental Disorder Prevalence Study (MDPS), on which TAC was a partner of RTI International, used trained clinicians to estimate national prevalence of mental and substance use disorders among U.S. adults aged 18 to 65 from 2019 to 2023. A recent article from Psychiatric Services featuring data from the MDPS reported that 35% of people with schizophrenia who were included in this study had at least one comorbid substance use disorder. The most common comorbid substance use disorders were alcohol use disorder and cannabis use disorder, which both impacted approximately one in five people with schizophrenia. However, among people who had schizophrenia and a comorbid substance use disorder, only 10% had received treatment for their substance use disorder in the past year. People with schizophrenia and comorbid substance use disorders had a lower likelihood of antipsychotic treatment than those who only had schizophrenia. These findings emphasize the need for more robust outreach and treatment for comorbid substance use disorders among people with schizophrenia.
Recommendations for treating schizophrenia and comorbid substance use disorders. Comorbid substance use has been associated with negative outcomes for people with schizophrenia, including higher rates of hospitalization, suicide, mortality, co-occurring physical health conditions, and lower rates of treatment adherence, among others. It also may make side-effects of some antipsychotic medications more severe, according to a 2024 review article from Annals of General Psychiatry. Although people with schizophrenia and comorbid substance use disorders have historically been excluded from clinical research, the authors of this article provide several recommendations for successfully managing comorbid substance use disorders among clients with schizophrenia, including providing both psychosocial and pharmacological treatments in treatment plans, building a strong therapeutic alliance, and utilizing shared decision making to promote treatment adherence.
Clozapine relieves symptoms for people with schizophrenia and comorbid substance use. Treatment-resistant schizophrenia is considered to occur when at least two antipsychotic medications with different mechanisms fail to improve symptoms. Clozapine is the recommended medication for those with treatment-resistant schizophrenia. A 2025 study published in Journal of Psychopharmacology explored the effectiveness of clozapine among people with treatment-resistant schizophrenia or schizoaffective disorder. Seventy-three percent of study participants had substance use levels that were indicative of a comorbid substance use disorder. The study found that compared to other antipsychotic medications, only clozapine was a predictor of improvements in all symptom categories, including positive symptoms, negative symptoms, and symptoms of mood disorders, as well as improvements in substance use. These findings are consistent with a 2025 review article from Comprehensive Psychiatry, which found that clozapine was effective at managing symptoms of psychosis and decreasing substance use among people with psychosis with comorbid substance use disorders.
SMI Research Digest is a monthly public service by TAC that highlights new, impactful research on topics related to severe mental illness. If you would like to support TAC programs and publications, please consider making a donation today.
