Real-world effectiveness of psychiatric pharmacotherapies in reducing the risk of substance use- and psychiatric hospitalisations in cannabis use disorder - An exploratory nationwide register-based study.

BACKGROUND

Pharmacotherapies have shown limited efficacy in cannabis use disorder (CUD). This exploratory study examined the real-world effectiveness of commonly used psychiatric medications in reducing the risk of substance use and psychiatric hospitalisations among individuals with CUD.

METHODS

We conducted a nationwide prospective cohort study using Swedish health and administrative registers. The cohort included 51,947 individuals aged 16-64 years with a first CUD diagnosis (ICD-10 F12) between 2006 and 2021. Medication use was modelled as time-dependent with the PRE2DUP method. Within-individual Cox regression was used to compare hospitalisation risk during medication use versus non-use. The primary outcome was hospitalisation for substance use disorder (SUD).

RESULTS

ADHD (aHR: 0.85; 95% CI: 0.81-0.88) and SUD medications (aHR: 0.97; 0.93-0.99) were associated with reduced SUD hospitalisation risk. In contrast, antipsychotics (aHR: 1.12; 1.09-1.15), antidepressants (aHR: 1.09; 1.06-1.11), and benzodiazepines (aHR: 1.14; 1.11-1.17) were associated with increased risk, while mood stabilisers showed no significant effect. Specific agents, including clozapine (aHR: 0.47; 0.31-0.73), naltrexone (aHR: 0.79; 0.71-0.88), buprenorphine (aHR: 0.92; 0.88-0.96), lisdexamfetamine (aHR: 0.74; 0.69-0.79), methylphenidate (aHR: 0.90; 0.86-0.94), and ADHD polytherapy (aHR: 0.85; 0.75-0.96), were associated with reduced risk.

CONCLUSIONS

Most psychiatric medications were not associated with a reduced risk of SUD in individuals diagnosed with CUD. However, pharmacotherapies for ADHD, opioid or alcohol use disorder, and treatment-resistant schizophrenia were linked to better outcomes, likely reflecting the underlying clinical trajectories of other comorbid psychiatric disorders rather than direct therapeutic effects on CUD.