The Association Between Stimulant Medication Use and Mortality.

Purpose: To assess the association between prescription stimulant medication use and mortality through an analysis of data in the FDA Adverse Event Reporting System (FAERS) and of electronic health records (EHR) of adult patients at a large metropolitan health care center.

Methods: The first analysis estimated the associations between the report of a sudden death event in FAERS with stimulants (methylphenidate, dextroamphetamine, dextroamphetamine-amphetamine, and lisdexamfetamine) and with 30 medications unlikely to be associated with serious adverse cardiovascular events and sudden death (control medications); propensity score matching was used to control for confounding. The second analysis estimated the associations between all-cause mortality with stimulants and with control medications in an self-controlled case series (SCCS) of EHR data; the SCCS method assessed whether, within individuals, there was an association between initiation of stimulant medication and mortality in a subsequent risk period. Data from the FDA Adverse Event Reporting System (FAERS) and from electronic health records (EHR) of adult at a large metropolitan health care center were analyzed.

Results: In the FAERS analyses, dextroamphetamine and methylphenidate, as well as the combined stimulant class, were significantly associated with sudden death [dextroamphetamine: RR = 2.24 (95% CI: 1.37-3.65; adjusted P < 0.001); methylphenidate: RR = 2.30 (95% CI: 1.62-3.27; adjusted P < 0.001); stimulant class: RR = 2.02 (95% CI: 1.46-2.79; adjusted P < 0.001)]. In the SCCS analyses, these 2 stimulants as well as the stimulant class were significantly associated with all-cause mortality [dextroamphetamine: RR = 3.96 [95% CI: 2.07-7.56; adjusted P < 0.001); methylphenidate: RR = 4.11 (95% CI: 1.78-9.50; adjusted P < 0.001); stimulant class: RR = 3.53 (95% CI: 1.73-7.20; adjusted P < 0.001)]. In the SCCS analysis, for all stimulants except lisdexamfetamine, the RR increased with the age at first stimulant use.

Conclusions: The current results document a significant association between stimulant use and mortality and underscore existing guidance to assess current cardiovascular disease and risk factors when prescribing stimulants, especially for older adults.