Psychiatric Comorbidities in Substance Use Disorders: Sex-Based Differences in a National Real-World Clinical Sample

Substance use disorders (SUDs) are associated with risk of psychiatric comorbidities, with inconsistent sex differences across studies. The objective of this study was to determine odds of psychiatric comorbidities based on sex in persons with a primary diagnosis of opioid, alcohol, or cannabis dependence, using a national clinical dataset.

This was a cross-sectional study of data from state-funded and state-run mental health programs in 2022 (Mental Health Client-Level Data, from the U.S. Substance Abuse and Mental Health Services Administration). Data were obtained from adults (age ≥18 years) with a primary diagnosis of either opioid (N=28,808), alcohol (N=23,281), or cannabis dependence (N=5,961). Data from individuals with each SUD were examined for psychiatric comorbidity outcomes, based on secondary diagnoses of an anxiety disorder, bipolar disorder, a depressive disorder, schizophrenia or other psychotic disorder, or a trauma- and stressor-related disorder versus no comorbidity. Data were analyzed with multinomial logistic regressions, examining sex, race, ethnicity, and age as predictors.

Males with a primary diagnosis of opioid, alcohol, or cannabis dependence had lower adjusted odds of anxiety, bipolar, depressive, and trauma- and stressor-related disorders compared to females. However, males with opioid or cannabis dependence had higher adjusted odds of schizophrenia or other psychotic disorders compared to females. Adjusted analyses also detected associations of race and ethnicity with specific comorbidities.

In this recent national clinical dataset, sex-based differences were observed in specific psychiatric comorbidities for each of these three SUDs. Future studies should examine biopsychosocial mechanisms that underlie these differences, with the goal of improving personalized care.