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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    • "), and clinical advantages in terms of sleep (Prasad and Steer 2008) and comorbidities with tics (Allen et al. 2005) and anxiety (Geller et al. 2007). Results from double-blinded, randomized, placebo-controlled trials show that the effect sizes for methylphenidate in patients with ADHD range from 0.5 to 1.0 (Wolraich et al. 2001; Wilens et al. 2006), whereas those for atomoxetine range from 0.6 to 1.3 (Svanborg et al. 2009; Martenyi et al. 2010). "
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    ABSTRACT: The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported more often for OROS-methylphenidate than for atomoxetine. After 24 weeks of treatment, OROS-methylphenidate and atomoxetine had comparable efficacy in reducing core ADHD symptoms in drug-naïve children and adolescents with ADHD.
    Full-text · Article · Jul 2015 · Journal of Child and Adolescent Psychopharmacology
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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.
    Full-text · Article · Aug 2010 · Journal of child and adolescent psychopharmacology
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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.
    Full-text · Article · May 2009 · BMC Psychiatry
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