Steven L. Linder

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

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Cyclic vomiting syndrome in adults

Abstract  Cyclic vomiting syndrome (CVS) was initially described in children but can occur in all age groups. Cyclic vomiting syndrome is increasingly recognized in adults. However, the lack of awareness of CVS in adults has led to small numbers of diagnosed patients and a paucity of published data on the causes, diagnosis and management of CVS in adults. This article is a state‐of‐knowledge overview on CVS in adults and is intended to provide a framework for management and further investigations into CVS in adults.

Use of the ICHD-II criteria in the diagnosis of pediatric migraine

Objective.—To evaluate the sensitivity of the new International Classification of Headache Disorders‐2nd edition (ICHD‐II) criteria in the diagnosis of childhood migraine and to propose specific criteria for the diagnosis of childhood migraine.

Subcutaneous Sumatriptan in the Clinical Setting: The First 50 Consecutive Patients With Acute Migraine in a Pediatric Neurology Office Practice

An open prospective study was undertaken to assess the efficacy and safety of subcutaneous sumatriptan in 50 consecutive children ages 6 to 18 years with severe migraine. There were 28 females and 22 males. The dose of sumatriptan was 0.06 mg/kg. Parameters included overall efficacy, time to relief, recurrence rate, adverse events, and objective global rating. Overall efficacy, defined by headache reduction from severe or moderate to mild or none, was 78%. Twenty‐six percent responded within 30 minutes, 46% responded in 60 minutes, and 6% responded between I to 2 hours. Twenty‐two percent had no response or a suboptimal response. Recurrence rate was only 6%. There was a difference in efficacy between male and female, as 91% of the males responded, while only 68% of the females responded. The males had more migraine alone while the females had migraine often with a coexistent tension‐type headache. Eighty percent of all the patients had some adverse event which was usually mild and transient; however, one patient developed a transitory confusional state which resolved in 2 hours. Eighty‐four percent reported a global rating of good to excellent, while 16% rated the treatment only fair to poor. These findings suggest that subcutaneous sumatriptan can be both effective and safe in childhood migraine, especially in dealing with migraine alone,

Obesity in the Pediatric Headache Population: A Multicenter Study

Objective.— To examine the prevalence of obesity, the relationship between weight compared with headache frequency and disability, and effect of weight change on headache outcomes within a pediatric headache population.

Efficacy and Tolerability of Almotriptan in Adolescents: A Randomized, Double-Blind, Placebo-Controlled Trial

Objectives.— To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents.

Atomoxetine Treatment of ADHD in Children With Comorbid Tourette Syndrome

Objective: This study examines changes in severity of tics and ADHD during atomoxetine treatment in ADHD patients with Tourette syndrome (TS). Method: Subjects (7-17 years old) with ADHD (Diagnostic and Statistical Manual of Mental Disorders, DSM-IV) and TS were randomly assigned to double-blind treatment with placebo (n = 56) or atomoxetine (0.5-1.5 mg/kg/day, n = 61) for approximately 18 weeks. Results: Atomoxetine subjects showed significantly greater improvement on ADHD symptom measures. Treatment was also associated with significantly greater reduction of tic severity on two of three measures. Significant increases were seen in mean pulse rate and rates of treatment-emergent nausea, decreased appetite, and decreased body weight. No other clinically relevant treatment differences were observed in any other vital sign, adverse event, laboratory parameter, or electrocardiographic measure. Conclusion: Atomoxetine is efficacious for treatment of ADHD and its use appears well tolerated in ADHD patients with comorbid TS. (J. of Att. Dis. 2008; 11(4) 470-481)

Eletriptan for the acute treatment of migraine in adolescents: Results of a double-blind, placebo-controlled trial

Background.—Eletriptan is a potent 5‐HT1B/1D agonist with proven efficacy in the acute treatment of migraine in adults.

Randomized Trial of Sumatriptan and Naproxen Sodium Combination in Adolescent Migraine

BACKGROUND: Treatment of adolescent migraine remains a significant unmet medical need. We compared the efficacy and safety of 3 doses of sumatriptan and naproxen sodium (suma/nap) combination tablets to placebo in the acute treatment of adolescent migraine. METHODS: This randomized, parallel group study in 12 to 17 year olds required 2 to 8 migraines per month (typically lasting >3 hours untreated) for ≥6 months. Subjects entered a 12-week run-in phase, treating 1 moderate-to-severe migraine (attack 1) with single-blind placebo. Subjects reporting headache pain 2 hours after dosing were randomly assigned into a 12-week double-blind phase, treating 1 moderate-to-severe migraine (attack 2) with placebo (n = 145), suma/nap 10/60 mg (n = 96), 30/180 mg (n = 97), or 85/500 mg (n = 152). The primary end point was the percentage of subjects pain-free at 2 hours. RESULTS: The attack 2 adjusted (age; baseline pain severity) 2-hour pain-free rates were higher with suma/nap 10/60 mg (29%; adjusted P = .003), 30/180 mg (27%; adjusted P = .003), and 85/500 mg (24%; adjusted P = .003) versus placebo (10%). Posthoc primary end-point analyses did not demonstrate differences among the 3 doses or an age-by-treatment interaction. Statistically significant differences were found for 85/500 mg versus placebo for sustained pain-free 2 to 24 hours (23% vs 9%; adjusted P = .008), 2-hour photophobia-free (59% vs 41%; adjusted P = .008), and 2-hour phonophobia-free (60% vs 42%; adjusted P = .008). Analyses of other pain, associated symptoms, rescue medication use, and health outcome end points supported higher efficacy for active doses versus placebo. All active doses were well tolerated. CONCLUSIONS: All doses of suma/nap were well tolerated, providing similarly effective acute treatment of adolescent migraine pain and associated symptoms, as compared with placebo.

Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents.

Objectives.— To evaluate the long‐term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents.