Pre-Existing Comorbid Emotional Symptoms Moderate Short-Term Methylphenidate Adverse Effects in a Randomized Trial of Children with Attention-Deficit/Hyperactivity Disorder

Abstract

Objective: We sought to ascertain whether baseline anxiety/depression and oppositional defiant disorder (ODD) symptoms impacted the experience of short-term methylphenidate (MPH) adverse effects (AEs) in 7- to 11-year-old children with attention-deficit/hyperactivity disorder (ADHD) (n = 171) undergoing a double-blind MPH crossover trial. Method: The Vanderbilt ADHD Diagnostic Parent Rating Scale measured baseline child anxiety/depression and ODD symptomology. The parent-completed Pittsburgh Side Effect Rating Scale assessed the AEs of anxiety, sadness, and irritability at baseline, on placebo, and on three MPH dosages. For each AE, we evaluated comorbidity main effects, dose main effects, and comorbidity × dose interactions. Results: Baseline anxiety/depression × dose and ODD × dose interactions were significant for the AEs of anxiety, sadness, and irritability. Compared with premedication baseline, these AEs attenuated on MPH for children with initially higher comorbidity symptoms, whereas those with initially lower comorbidity symptoms tended toward no change or increasing AE levels. Conclusion: Premedication anxiety/depressive and ODD symptoms may be important predictors of short-term MPH emotional AEs.

Keywords: ADHD; adverse effects; methylphenidate; side effects; stimulants.

FIG. 1.

Anxiety adverse effect ratings during baseline, placebo, and high dose methylphenidate conditions by level of premedication anxiety/depression symptoms. ln, natural log of adverse effect rating, with dashed lines indicating the ln score that corresponds to adverse effect parent ratings of mild, moderate, and severe. SD, standard deviation.

FIG. 2.

Sadness adverse effect ratings during baseline, placebo, and high dose methylphenidate conditions by level of premedication anxiety/depression symptoms. ln, natural log of adverse effect rating, with dashed lines indicating the ln score that corresponds to adverse effect parent ratings of mild, moderate, and severe. SD, standard deviation.

FIG. 3.

Irritability adverse effect ratings during baseline, placebo, and high dose methylphenidate conditions by level of premedication ODD symptoms. ln, natural log of adverse effect rating, with dashed lines indicating the ln score that corresponds to adverse effect parent ratings of mild, moderate, and severe. ODD, oppositional defiant disorder; SD, standard deviation.