Results of N=1 randomized, double-blind, placebo-controlled, cross-over discontinuation trials embedded in clinical practice after longer term methylphenidate use: A pilot study

Abstract

Background Attention-deficit/hyperactivity (ADHD) guidelines recommend that the need for continued stimulant medication treatment of children and adolescents needs to be reviewed at least annually. We aimed to assess the outcomes in clinical practice of placebo-controlled discontinuation trials after long-term methylphenidate treatment. Method We asked clinicians to implement N=1 randomized, double-blind, placebo-controlled, cross-over discontinuation trials after at least one year of methylphenidate treatment of children and adolescents (n = 26, 6 – 15 years of age). We analyzed the effectiveness of ongoing methylphenidate treatment compared to placebo on symptoms of ADHD, oppositional defiant disorder, and conduct disorder according to both parents and teachers, and the global improvement or deterioration according to the clinicians. We also assessed the proportion of individuals who continued using methylphenidate after the discontinuation trial. Results Teacher-rated hyperactivity and impulsivity symptoms were significantly lower during methylphenidate treatment compared to placebo (β = 3.80, SD = 1.69, t = 2.25, p = .04). No other significant differences were found between methylphenidate and placebo. Almost two-thirds (n = 16, 61.5%) of individuals continued using methylphenidate after the discontinuation trials, of which 7 did not deteriorate during placebo according to their clinician. Discussion Our findings support the need for regular evaluations of methylphenidate treatment effectiveness and emphasize the importance of including the school setting when evaluating treatments. Better guidance for clinicians when to continue or cease methylphenidate treatment is urgently needed.