Pharmacotherapies for Attention-Deficit/Hyperactivity Disorder and Risk of Suicidal Behavior: A Within-Individual Study of Stimulants, Atomoxetine, and Alpha-2 Agonists

Abstract

Background: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for suicidal behavior. Stimulant and nonstimulant pharmacotherapies are widely prescribed for ADHD, but their effects on suicidal behavior remain unclear. Methods: In a U.S. commercial health care insurance claims database, we identified 830,352 individuals diagnosed with ADHD, ages 9 to 64 years, who used at least 1 stimulant, atomoxetine, or alpha-2 agonist medication between 2016 and 2021. We examined the proportions of patients with suicidal behavior (i.e., emergency department visits or hospitalizations for suicide attempts or intentional self-harm) in the months preceding and following treatment initiation. Then, we used a within-individual design to evaluate associations between each medication and risk of suicidal behavior, while accounting for time-varying covariates. Finally, we examined associations for stimulants among subgroups defined by sex, age, and race-ethnicity. Results: Compared with other off-treatment periods, rates of suicidal behavior were elevated during the 2 months before starting ADHD pharmacotherapy, particularly for atomoxetine (odds ratio [OR] = 2.63 [95% CI, 2.28-3.04]) and alpha-2 agonists (OR = 2.99 [2.64-3.40]). Compared with off-treatment periods (excluding pretreatment), the odds of suicidal behavior were slightly elevated during treatment (ORstimulants = 1.11 [95% CI, 1.04-1.18], ORatomoxetine = 1.17 [1.00-1.38]; ORalpha agonists = 1.31 [1.15-1.49]). Findings were similar across most patient subgroups. Conclusions: Within-individual comparisons suggested that risk of suicidal behavior was higher just before and, to a lesser extent, during ADHD medication treatment compared with off-treatment. Further research is needed to determine whether elevations in risk during treatment are attributable to medication effects or to unmeasured time-varying confounding factors, such as a continuation (although attenuated) of the increased risk observed before pharmacotherapy.