NAVIGATING THE PHARMACOTHERAPY GAP IN AMPHETAMINE-TYPE STIMULANT USE DISORDER: A REVIEW OF OFF-LABEL EVIDENCE

Authors

• Nicole Sugumaran, University of LynchburgFollow

Specialty

addiction medicine

Advisor

Dr. Salzar

Abstract

Contingency management remains the primary standard of care for amphetamine-type stimulant use disorder (ATSUD) due to an absence of FDA-approved pharmacotherapies. Addressing this treatment gap, this review evaluated clinical trials of off-label agents for moderate-to-severe ATSUD, including topiramate, mirtazapine, bupropion plus extended-release naltrexone, and prescription psychostimulants. Across drug classes, evaluated medications demonstrated modest efficacy signals. Topiramate reduced median urine methamphetamine levels and severity of dependence; mirtazapine significantly decreased use days (mean reduction = 2.2 days; p = 0.02); combination bupropion–naltrexone achieved a significant 11.1 percentage-point response advantage over placebo (p < 0.001); and methylphenidate significantly improved participant retention (p < 0.05). Traditional trial designs reliant on strict abstinence metrics frequently obscure partial therapeutic benefits and clinically meaningful functional gains. To unmask efficacy signals and establish a pathway toward regulatory approval, future studies must transition to contingency management (CM) -anchored designs (comparing CM plus active drug against CM plus placebo), incorporate validated functional outcome thresholds, and utilize longer evaluation periods.

Recommended Citation

Sugumaran N. NAVIGATING THE PHARMACOTHERAPY GAP IN AMPHETAMINE-TYPE STIMULANT USE DISORDER: A REVIEW OF OFF-LABEL EVIDENCE. University of Lynchburg Doctoral Project Assignment Repository. 2026; 8(3).