Placebo-controlled evaluation of Ritalin side effects

OBJECTIVE: To address the frequency of side effects of Ritalin therapy in children with attention deficit hyperactivity disorder (ADHD) using the Barkeley Side Effects Questionnaire (BSEQ) in a clinical setting. DESIGN: Randomized double-blind placebo-controlled cross-over trial. SETTING: A large rural tertiary care clinic. PATIENTS: 234 consecutive children aged 5 through 15 years who met the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) criteria for ADHD were enrolled. Of these children, 206 had sufficient side effects data for analysis. INTERVENTIONS: 0.3 mg/kg per dose and 0.5 mg/kg per dose Ritalin compared to placebo in separate 2-week trials. Each treatment was given three times a day for 7 consecutive days. MEASUREMENTS AND MAIN RESULTS: Parents, blinded to the treatment assignment, assessed side effects via the BSEQ at baseline and at the end of each of the 4 treatment weeks. Univariate odds ratios (OR) were used to describe the magnitude of differences in observed side effects between Ritalin and placebo weeks of the trial for each of the items on the BSEQ. The frequency of the following side effects significantly increased with Ritalin therapy: insomnia (OR = 3.13, 95% confidence interval [CI] = (1.80,5.42)), appetite disturbance (OR = 19.00, 95% CI = (9.18,39.31)), stomachache (OR = 7.00, 95% CI = (3.29, 14.89)), headache (OR = 5.29, 95% CI = (2.51,11.15)), and dizziness (OR = 7.50, 95% CI = (1.93,29.13)). The frequency of the following side effects significantly decreased with Ritalin therapy: staring and daydreaming (OR = 0.47, 95% CI = (0.27,0.84)), irritability (OR = 0.33, 95% CI = (0.18,0.61)), anxiety (OR = 0.42, 95% CI = (0.23,0.76)), and nailbiting (OR = 0.19, 95% CI = (0.07, 0.53)). The incidence rates of the remaining BSEQ items did not differ significantly between the Ritalin and placebo weeks of the trial. CONCLUSION: The BSEQ proved to be clinically effective in tracking Ritalin side effects and should be incorporated into the routine evaluation and monitoring of ADHD patients for whom stimulants are prescribed.