Risk of Suicidal Event with Stimulant Treatment: A Self-Controlled Case Series Study

Abstract

Background: Patients with attention‐deficit/hyperactivity disorder (ADHD) have an increased risk of suicide attempt. Stimulants such as methylphenidate (MPH) are the first‐line treatment for ADHD, but their relationship to suicide attempts is unclear. Objectives: To investigate the association between MPH and the risk of suicide attempt. Methods: We used database from Hong Kong population‐based electronic medical records on the Clinical Data Analysis & Reporting System to identify individuals ages 6 to 25 with MPH medication from 2001 to 2015. Among them, individuals who had incident suicide attempt within the study period were included in the analysis. We applied the self‐controlled case series design to control for time‐invariant characteristics of the patients and time trends in the exposure. Relative incidence of suicide attempt comparing periods when patients were exposed to MPH with non‐exposed periods was evaluated. Results: Among 25,825 patients with MPH prescriptions, 154 had incident suicide attempt within the observation period. The overall incidence of suicide attempt during MPH treatment was 9.27 per 10,000 patient‐years. For all cases, an increased risk of suicide attempt was detected during the 90‐day period before MPH was first started, with an incidence rate ratio (IRR) of 6.54 (95%CI 3.37 to 12.72). The IRR remained raised during the first 90 days of treatment with IRR of 3.91 (95%CI 1.62 to 9.42), before returning to baseline levels with prolonged treatment (IRR = 1.35; 95%CI 0.77 to 2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempt was not increased (IRR = 0.78; 95%CI 0.26 to 2.35). Further analysis using non‐parametric spline‐based SCCS showed that the risk of suicide attempt increased before the initiation of MPH treatment and decreased along with the MPH exposure. Conclusions: The incidence of suicide attempt was higher in the periods both immediately before and immediately after the start of MPH treatment. This suggests that the observed increased risks of suicide attempt linked to the start of treatment may reflect changes in behavioural and attentional symptoms that led to psychiatric consultations and associated with the decision to begin treatment rather than any causal effect of the medication.