Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis

Objective: Examine patterns of adult medical use of amphetamine and methylphenidate stimulant drugs, classified in the USA as Schedule II controlled substances with a high potential for psychological or physical dependence.

Design: Cross-sectional study.

Setting and participants: Prescription drug claims for US adults, age 19-64 years, included in a commercial insurance claims database with 9.1 million continuously enrolled adults from 1 October 2019, through 31 December 2020. Stimulant use was defined as adults filling one or more stimulant prescriptions during calendar 2020.

Outcome measures: The primary outcome was an outpatient prescription claim, service date and days' supply for central nervous system (CNS)-active drugs. Combination-2 was defined as 60 days or more of combination treatment with a Schedule II stimulant and one or more additional CNS-active drugs. Combination-3 therapy was defined as the addition of 2 or more additional CNS-active drugs. Using service date and days' supply, we examined the number of stimulant and other CNS-active drugs for each of the 366 days of 2020.

Results: Among 9 141 877 continuously enrolled adults, the study identified 276 223 individuals (3.0%) using Schedule II stimulants during 2020. They filled a median of 8 (IQR, 4-11) prescriptions for these stimulant drugs that provided 227 (IQR, 110-322) treatment days of exposure. Among this group, 125 781 (45.5%) combined use of one or more additional CNS active drugs for a median of 213 (IQR, 126-301) treatment days. Also, 66 996 (24.3%) stimulant users used two or more additional CNS-active drugs for a median of 182 (IQR, 108-276) days. Among stimulants users, 131 485 (47.6%) were exposed to an antidepressant, 85 166 (30.8%) filled prescriptions for anxiety/sedative/hypnotic medications and 54 035 (19.6%) received opioid prescriptions.

Conclusion: A large proportion of adults using Schedule II stimulants are simultaneously exposed to one or more other CNS-active drugs, many with tolerance, withdrawal effects or potential for non-medical use. There are no approved indications and limited clinical trial testing of these multi-drug combinations, and discontinuation may be challenging.