Use of CONCERTA in Patients with Tic Disorders

SUMMARY

• According to the prescribing information, the use of CONCERTA in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome is contraindicated.¹
• Studies have been conducted to assess the hypothesis that stimulants can cause, provoke or exacerbate tics and Tourette’s syndrome with no confirmation.^2-7
• Palumbo et al (2004)⁷ analyzed the incidence of tics in children and adults with ADHD treated with CONCERTA across 5 studies:
  • In placebo-controlled studies (Studies 1-3), tics were reported in 4% for patients (9/224) treated with CONCERTA; all 9 patients had a history of tics.
  • In a long-term (2-years), open-label study (Study 4), tics as adverse events were reported in 9.8% of patients (40/407) over the 2-year treatment period.
    • The risk of tics was higher in patient with a history of tics than in those without (33% vs 7%, respectively; P<0.0001).
    • No correlation was found between the dose of CONCERTA and the frequency of tic episodes.
  • In a long-term (9-months), open-label study (Study 5), tics as adverse events were reported in 1.2% of patients (13/1082; safety population).
    • Three of these 13 patients had a history of tics.
• The use of CONCERTA in patients with ADHD and Tourette’s syndrome has been documented in 2 case reports.^8,9

PRODUCT LABELING

Please refer to the enclosed Full Prescribing Information.¹

BACKGROUND

Stimulants have been hypothesized to cause, provoke or exacerbate tics and Tourette’s Syndrome. Many authors have investigated this hypothesis with no confirmation from clinical observation and controlled trials.^2-7

CLINICAL DATA

Incidence of Tics in Children and Adults with ADHD

Palumbo et al (2004)⁷ analyzed the incidence of tics in children and adults with ADHD treated with CONCERTA across 5 studies.

Study Design/Methods

Analyses on the incidence of tics were conducted using pooled data from 3 short-term, placebo-controlled studies (Study 1, 2, and 3); separate analyses were conducted for each of the 2 long-term, open-label studies (Study 4: 2-years, and Study 5: 9-months). Patients with mild or moderate tics (without a diagnosis of Tourette’s syndrome) were eligible to enroll in any of the 5 studies. In Studies 1-4, the parents were asked if their child had experienced tics during the time since the last study visit; new onset and change in severity were also assessed. In Studies 4 and 5, tics were reported as adverse events.

Results

Studies 1-3

• In the placebo-controlled studies, 224 children aged 6-13 years were treated with CONCERTA and 13% of these patients (29/224) had a history of tics.
• Tics were reported in 4% for patients (9/224) treated with CONCERTA. The difference between treatment groups was not statistically significant (CONCERTA, 4%; MPH IR, 2.3%; placebo, 3.7%).
  • In the CONCERTA group, all 9 patients who reported tics during the study had a history of tics.

Study 4

• Of the 407 children aged 6-13 years who participated in the first year of this open-label study, 11.8% (48/407) had a history of tics.
• Tics were experienced by approximately 5% of patients each month (most were not new onsets), and the severity remained unchanged or improved over the 12-month period.
• During the 2-year treatment period, tics as adverse events were reported in 9.8% of patients (40/407).
  • Of these 40 patients, 16 had a prior history of tics.
  • The majority of these events were mild or moderate in severity.
  • The risk of tics was 33% in patients with a history of tics and 7% in those without a history of tics (P<0.0001).
    • A statistically significant difference was observed in the mean duration of tics between patients with or without a history of tics (165 vs 79 days, respectively; P=0.0318).
    • No significant differences were observed between those with or without a history of tics in the mean number of tic episodes per patient (1.56 vs 1.58, respectively), and the mean time to first tic episode (204 vs 191 days, respectively).
  • No correlation was found between the dose of CONCERTA and the frequency of tic episodes.
  • Throughout the 2-year treatment period, 2% of patients (8/407) discontinued CONCERTA because of tics (history of tics, n=3; no history of tics, n=5).

Study 5

• Tics as adverse events were reported in 1.2% of patients (13/1082; safety population). See table Frequency of Tics During the Study.
• The majority of tic events were mild or moderate in severity; 2 patients experienced severe tics.
• Approximately 0.6% of patients (7/1082) discontinued treatment because of tics.

Use of CONCERTA in Children with ADHD and Tourette’s Syndrome

Jaworowski et al (2006)⁸ described a case report in which atomoxetine and CONCERTA were successfully used concomitantly in a child with ADHD, comorbid bipolar disorder, and Tourette’s syndrome.

• The boy was diagnosed with ADHD, obsessive-compulsive disorder (OCD), and oppositional-defiant disorder (ODD) at 5 years old.
• He experienced motor and vocal tics after treatment with methylphenidate and was diagnosed with Tourette’s syndrome for which he was successfully treated with haloperidol, methylphenidate, and risperidone.
• He was referred for psychopharmacological review at the age of 10 years after being hospitalized for 6 months due to major mood disturbances and threats of harming himself and his baby brother. He was discharged on valproic acid, clonidine, and ziprasidone.
• Due to significant difficulties with concentration, distractibility, and multiple motor tics, the child was given atomoxetine 0.5 mg/kg/day, which was gradually increased to 1.2 mg/kg/day (50 mg/day) over a 2-week period.
• Although the child experienced some improvement in concentration, he continued to exhibit impulsive and disruptive behavior, so CONCERTA 18 mg/day was added in order to augment the effect of atomoxetine.
• The dose of CONCERTA was increased from 18 mg/day to 36 mg/day which resulted in a dramatic improvement in behavior both at school and at home.
• Despite improvement in behavior, the child demonstrated some increase in motor tics, which was then managed by increasing the clonidine dose from 75 µg/day to 150 µg/day in 3 divided doses. Positive behavior changes and improved concentration were maintained for up to a year.

Lan et al (2015)⁹ described a case report of a 15-year-old boy with severe Tourette’s syndrome and ADHD who was temporarily treated with CONCERTA.

• The child was diagnosed with Tourette’s syndrome and ADHD at the age of 9 years and was initially treated with clonidine 37.5 µg/day and CONCERTA 36 mg/day.
• Risperidone 1.5 mg/day was added to his treatment regimen, and the dose was gradually increased to 3 mg/day as his tic symptoms progressed.
• At age 12, he experienced significant worsening of tics and was started on atomoxetine 50 mg/day. CONCERTA was discontinued.
• He was unable to tolerate atomoxetine and was restarted on CONCERTA 18 mg/day plus clonazepam 0.5 mg/day.
• The patient continued to experience severe motor tics and CONCERTA was discontinued due to unsatisfactory response. Further adjustments were made to his antipsychotic treatment.
• His tic disorder was eventually controlled with a combination of clozapine 50 mg/day and quetiapine 200 mg/day. Improvements were maintained for more than 1 year and up to the time of this publication.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 13 February 2025.