Association between Attention Deficit Hyperactivity Disorder Medication and Depression: A 10-year Follow-up Self-controlled Case Study

OBJECTIVE: There is clinical concern that the stimulant methylphenidate (MPH) might increase the risk of depression, particularly in children. This study aimed to investigate the association between MPH use and the risk of depression. METHODS: A population-based electronic medical records database was used. We obtained claims data for prescription of ADHD medication, diagnosis of depression, and prescription of antidepressant medication between January 2007 and December 2016 for 43,259 individuals aged 6 to 19 who were diagnosed with ADHD between July 1, 2007 and December 31, 2007. The final analysis was based on 2,330 eligible participants. A self-controlled case series design was used to identify risk factors for major depressive disorder (MDD). RESULTS: An elevated MDD risk was found during the 90 days before MPH exposure, with an incidence rate ratio (IRR) of 12.12 (95% confidence interval [95% CI] 10.06−14.61, p < 0.0001). During methylphenidate treatment, the IRR was 18.06 with a 95% CI of 16.67 to 19.56 (p < 0.0001), but it returned to baseline levels after day 31 of MPH treatment discontinuation. The IRR for patients aged 6 to 9 years was 13.11 (95% CI 9.58−17.95) during the 90 days before MPH exposure, and 17.7 (95% CI 15.6−20.08) during MPH treatment, but returned to baseline levels after discontinuation of MPH treatment. CONCLUSION: We confirmed the temporal relationship between depression and methylphenidate use in young people with ADHD. Though the absolute risk is low, the risk of depression should be carefully considered, particularly in the period directly following the start of methylphenidate treatment.