Objectives: To study the effects of discontinuation of long-term methylphenidate use on secondary outcome measures of strengths and difficulties, quality of life (QoL), and parenting stress. Methods: Ninety-four children and adolescents aged 8 to 18 years who had used methylphenidate for over 2 years were randomly assigned to double-blind continuation of treatment for 7 weeks (36 or 54 mg extended release methylphenidate) or to gradual withdrawal over 3 to 4 weeks placebo. We used mixed models for repeated measures to investigate effects on parent, teacher, and child ratings of hyperactivity/inattention and comorbid symptoms with the Strengths and Difficulties Questionnaire (SDQ), investigator- and teacher-rated oppositional symptoms (Conners Teacher Rating Scale-Revised: short form [CTRS-R:S]), and parent-rated aggression with the Retrospective Modified Overt Aggression Scale. QoL was assessed with the Revised Questionnaire for Children and Adolescents to record health-related quality of life and parenting stress with the Nijmegen Parental Stress Index. Results: Hyperactivity/inattention scores from the parent- and teacher-rated SDQ (difference in mean change over time of respectively: -1.1 [95% confidence interval, CI, -2.0 to -0.3]; p = 0.01; -2.9 [95% CI -2.9 to -0.7; p = 0.01]) and oppositional scores of the teacher-rated CTRS-R:S (difference in mean change -1.9 95% CI [-3.1 to -0.6; p < 0.01]) deteriorated to a significantly larger extent in the discontinuation group than in the continuation group. We did not find effects on other symptom domains, aggression, QoL, and parenting stress after discontinuation of methylphenidate. Conclusion: Our study suggests beneficial effects of long-term methylphenidate use beyond 2 years for oppositional behaviors in the school environment. Similarly, beneficial effects were found on hyperactivity-inattention symptoms as rated by parent and teacher scales, confirming our primary study on investigator ratings of attention-deficit/hyperactivity disorder. However, discontinuation of methylphenidate did not appear to have impact on other comorbid problems or aspects of the child's or parental functioning.

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