Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorder

Harvard University, Cambridge, Massachusetts, United States
Neurology (Impact Factor: 8.29). 12/2005; 65(12):1941-9. DOI: 10.1212/01.wnl.0000188869.58300.a7
Source: PubMed


To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders.
Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks.
Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures.
Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

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Available from: Donald L Gilbert, Aug 26, 2015
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    • "ADHD symptom reduction was modest. Tics did not worsen but rather, on average, improved, *25% in the atomoxetine group versus 15% in the placebo group, which was significant at the trend level (Allen et al. 2005). An unusual study design feature allowed for early withdrawal but continued eligibility to receive medication in an open-label extension, creating an incentive for blinded investigators to withdraw nonresponders early and treat them openly. "
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    ABSTRACT: Tics are intermittent, repetitive, patterned but usually nonrhythmic motor movements or sounds performed in response to urges or involuntarily. They are the cardinal symptom required for a DSM-IV-TR diagnosis of Tourette's disorder (TD). Many children with TD present with mild tics that cause no significant impairment. However, when tics cause pain or interference, medical treatment is reasonable. This article reviews current evidence for treatment of tics in TD with medications as well as deep brain stimulation and transcranial magnetic stimulation. It concludes with some context for understanding this literature, relevant to treatment decisions and future treatment research in TD.
    Journal of child and adolescent psychopharmacology 08/2010; 20(4):263-76. DOI:10.1089/cap.2010.0015 · 2.93 Impact Factor
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    • "c. Probabilities of response in stimulant-naïve patients in whom stimulants are contra-indicated are based on responder rates from a randomised placebo-controlled trial of atomoxetine in patients with tics or Tourette's syndrome [41]. "
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    ABSTRACT: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurobehavioural disorder, affecting 3-6% of school age children and adolescents in Spain. Methylphenidate (MPH), a mild stimulant, had long been the only approved medication available for ADHD children in Spain. Atomoxetine is a non-stimulant alternative in the treatment of ADHD with once-a-day oral dosing. This study aims to estimate the cost-effectiveness of atomoxetine compared to MPH. In addition, atomoxetine is compared to 'no medication' for patient populations who are ineligible for MPH (i.e. having stimulant-failure experience or co-morbidities precluding stimulant medication). An economic model with Markov processes was developed to estimate the costs and benefits of atomoxetine versus either MPH or 'no medication'. The incremental cost per quality-adjusted life-year (QALY) was calculated for atomoxetine relative to the comparators. The Markov process incorporated 14 health states, representing a range of outcomes associated with treatment options. Utility values were obtained from the utility valuation survey of 83 parents of children with ADHD. The clinical data were based on a thorough review of controlled clinical trials and other clinical literature, and validated by international experts. Costs and outcomes were estimated using Monte Carlo simulation over a 1-year duration, with costs estimated from the perspective of the National Health Service in Spain. For stimulant-naive patients without contra-indications to stimulants, the incremental costs per QALY gained for atomoxetine were euro 34,308 (compared to an immediate-release MPH) and euro 24,310 (compared to an extended-release MPH). For those patients who have stimulant-failure experience or contra-indications to stimulants, the incremental costs per QALY gained of atomoxetine compared to 'no medication' were euro 23,820 and euro 23,323, respectively. The economic evaluation showed that atomoxetine is an effective alternative across a range of ADHD populations and offers value-for money in the treatment of ADHD.
    BMC Psychiatry 05/2009; 9(1):15. DOI:10.1186/1471-244X-9-15 · 2.21 Impact Factor
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    • "Given that stimulant medications have been associated with the onset or exacerbation of a tic disorder, atomoxetine may offer unique efficacy and/or tolerability in children with ADHD and comorbid tic disorders; Tourette’s syndrome (TS), and/or simple motor tic disorder. In the largest study to date, Allen et al49 examined children (7–17 years) with ADHD and concurrent TS or chronic motor tic disorder in a double-blind randomized treatment study with placebo (n = 72) or atomoxetine (0.5–1.5 mg/kg/day, n = 76) for up to 18 weeks. Atomoxetine was associated with a greater reduction of tic severity at endpoint relative to placebo on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (−0.7 ± 1.2 vs −0.1 ± 1.0, p = 0.002); however significance was not reached in Yale Global Tic Severity Scale (YGTSS) total score, nor the Tic Symptom Self-Report total score. "
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    ABSTRACT: This review examines and summarizes the pharmacodynamic and pharmacokinetic properties, short- and longer-term efficacy, the moderating effect of comorbid disorders, as well as short- and long-term safety and tolerability of atomoxetine for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD). A systematic literature search was performed to review the extant literature on articles pertaining to the pharmacological treatment with atomoxetine in pediatric and/or adolescent ADHD. There is an extensive literature on atomoxetine; over 4000 children have participated in clinical trials of atomoxetine, demonstrating its short- and longer-term efficacy. In addition, studies have examined the moderating effect of comorbid disorders on atomoxetine response, as well as atomoxetine's therapeutic potential for other psychiatric conditions. Short- and longer-term safety and tolerability continue to be reported. Atomoxetine is indicated for both acute and maintenance/extended treatment of pediatric ADHD. Clinicians and families must be familiar with atomoxetine's evidence base, including its profile of clinical response and its possible effectiveness in the presence of comorbidity.
    Neuropsychiatric Disease and Treatment 02/2009; 5(1):215-26. DOI:10.2147/NDT.S3896 · 1.74 Impact Factor
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