Real-world effectiveness of various pharmacological treatments in methamphetamine/amphetamine use disorders

There are no medications approved by authorities for the treatment of amphetamine/methamphetamine dependence. No studies have investigated the effectiveness of pharmacological treatments concerning hard outcomes such as hospitalization and death. We aimed to investigate the real-world effectiveness of various pharmacotherapies in persons with (meth)amphetamine use disorder.

Cohort of persons with first-time diagnosis of (meth)amphetamine use disorder (N=13965, mean age 34.4, SD 13.0; 69.3% men) were identified from nationwide Swedish registers of inpatient and specialized outpatient care, sick leaves and disability pensions during 2006-2018. The risk of outcomes was assessed during the use of medications for attention-deficit hyperactive disorder, substance use disorders, antidepressants, mood stabilizers and benzodiazepines, compared with non-use of that medication class. We studied the primary outcomes (substance use-related hospitalization, and any hospitalization or death) during use versus no use of specific medications or medication classes by using each person as his/her own control in within-individual analysis (stratified Cox model) to minimize selection bias. Mortality was a secondary outcome and was studied by using between-individual analysis as traditional Cox models.

Lisdexamphetamine was the only medication associated with statistically significant beneficial finding in all 3 outcomes (adjusted Hazard Ratio: 0.82, 95% Confidence Interval: 0.72–0.94, p-value: 0.005 for substance use-related hospitalization; aHR: 0.86, 95% CI: 0.78–0.95, p: 0.003 for any hospitalization or death; aHR: 0.43, 95%CI: 0.24–0.76, p: 0.004 for all-cause mortality). Use of benzodiazepines was associated with significantly higher risk of substance use-related hospitalization (aHR: 1.17, 95%CI: 1.12–1.22, p: <0.001), any hospitalization or death (aHR: 1.20, 95%CI: 1.17–1.24, p: <0.001) and all-cause mortality (aHR: 1.39, 95%CI: 1.20–1.60, p: <0.001).

Use of lisdexamphetamine is associated consistently with the best comparative effectiveness among generally used medications in persons with (meth)amphetamine use disorder, encouraging the conduct of randomized controlled trials. Benzodiazepine use was associated with poor outcomes.