Partial Dopamine D2/3 Agonists and Dual Disorders: A Retrospective-Cohort Study in a Real-World Clinical Setting on Patients with Schizophrenia Spectrum Disorders and Cannabis Use Disorder.

Introduction/objective: Schizophrenia with substance use disorder is a complex clinical condition that may increase treatment resistance. Cannabis use disorder is frequently associated with psychosis and the causal link has still to be defined. Partial D2/3 agonists may ensure limbic dopamine release normalization while avoiding reduced frontocortical dopamine release, which would contribute to negative symptoms. We aimed to observe the clinical course of patients with schizophrenia comorbid with cannabis use disorder while being treated with oral or long-acting injectable D2/3 partial agonists.

Methods: We observed 96 young adults with schizophrenia/schizoaffective disorder comorbid with cannabis use disorder during 18 months of treatment with aripiprazole long-acting injectable or oral aripiprazole or brexpiprazole. The assessment comprised Clinical Global Impressions-Severity, Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Barratt Impulsiveness Scale, and Visual Analog Scale for Craving.

Results: Included were 17 women and 79 men (mean age = 26.89 ± 4.74 years). The sample responded favorably to treatment as assessed by all clinical scales, save for the impulsiveness scale which showed no significant change. The four treatment samples responded well without differences, but employing a general linear model, long-acting injectable aripiprazole and brexpiprazole were better and similar on all clinical and craving scales compared to oral aripiprazole and to other antipsychotics. Long-acting injectable aripiprazole fared better than brexpiprazole on general psychopathology, negative symptoms, and craving, while the reverse was true for global severity. However, the sample size imbalance did not allow for drawing strong conclusions. We found no significant treatment resistance in our 96-patient sample.

Conclusion: Partial D2/3 agonists may treat comorbid schizophrenia/schizoaffective disorder and cannabis use disorder, improving the symptoms of both disorders and substance craving.