Case Report: Four Purported Cases of Methylphenidate-Induced Tic Exacerbation: Methodological and Clinical Doubts

Abstract

The role of stimulant medication in the induction and exacerbation of tics in ADHD children has been controversial. We have identified four seemingly apparent cases of methylphenidateinduced tic exacerbation that, on closer examination, did not seem as convincing as initially perceived. Case reports are presented of these prepubertal children, who experienced a marked worsening of tics during medication evaluation or maintenance treatment. Patient A is a child with severe ADHD whose tic disorder gradually became more severe during methylphenidate treatment; he was found to have less severe tic symptoms when larger doses of medication were used. Patient B is an example of apparent methylphenidate-induced Tourette's syndrome in a child who had a preexisting but undiagnosed tic disorder despite multiple evaluations. Patients C and D illustrate how standard dosage titration procedures could lead to erroneous conclusions about medication and fluctuation in tic frequency. These case reports underscore the importance of unbiased and accurate information about pretreatment status, symptom fluctuation over time, and response to medication in making appropriate clinical management decisions. It is advised that clinicians and researchers carefully evaluate apparent links between tic exacerbation and stimulant use in individual cases.Although early reports of stimulant drug therapy for tic disorders were not particularly encouraging (Abuzzahab and Anderson 1976, Shapiro et al. 1988), it was not until the 1970s that the notion became well established that stimulants were contraindicated for the treatment of attentiondeficit hyperactivity disorder (ADHD) in child patients with tic disorder. This belief was based, in part, on reports that stimulant drugs could induce Gilles de la Tourette's syndrome (TS) (e.g., Bremness and

Tics and psychiatric comorbidity in children and adolescents

“…Because tics typically fluctuate in frequency and severity, even seemingly innocuous tics at time of referral can become implicated in later treatment planning. For example, worsening in pre-existing but undiagnosed tics consequent to stimulant drug treatment for ADHD may be falsely characterized as induction of tic disorder de novo (Sprafkin and Gadow 1993).…”

Long-term Methylphenidate Therapy in Children With Comorbid Attention-Deficit Hyperactivity Disorder and Chronic Multiple Tic Disorder

“…In 3 cases, treatment was terminated before the second follow-up visit owing to therapeutic improvement (n = 2) and concerns about tic exacerbation (n = 1), which a controlled trial with a reversal condition failed to confirm. 38 Four children were treated with an anti-tic medication in combination with methylphenidate at some time during the course of the follow-up (neuroleptic [n = 3] and clonidine [n = 1]). Two of these children were receiving anti-tic medication prior to the short-term dose trial, which was later reinstated throughout the entire follow-up interval, and 2 children began receiving anti-tic medication between the third and fourth follow-up.…”

“…This is best done with reversal designs, where the treatment condition that seemingly produces a worsening in tic symptoms is reintroduced at a later time to see if symptom exacerbation is replicable. 38 Nevertheless, data plots for individual children show considerable fluctuations in the frequency and severity of tics in children who are receiving maintenance methylphenidate therapy, which strongly suggests that spontaneous exacerbations of tic disorder symptoms are a natural occurrence. Furthermore, these fluctuations in tic symptoms likely explain some (but not necessarily all) reports of stimulant-induced tic exacerbations in children with preexisting tic disorder.…”

“…Furthermore, these fluctuations in tic symptoms likely explain some (but not necessarily all) reports of stimulant-induced tic exacerbations in children with preexisting tic disorder. 38 The implications of this phenomenon for clinical management and the importance of research methodology in the conduct of drug trials are self-evident.…”

Emergence of Tics in Children with ADHD: Impact of Once-Daily OROS® Methylphenidate Therapy

“…Effects on ADHD symptoms were maintained throughout the study period. Two additional studies, one in which children receiving stimulant medication were switched to a placebo under double-blind conditions to see if this decreased tic symptoms , and another in which stimulant medication was reintroduced to 4 children who had purportedly developed tics while on medication-to see if exacerbation could be replicated (Sprafkin and Gadow 1993)-also failed to show any effect of stimulant medication on the severity or frequency of tics.…”