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High-Dose Atomoxetine Treatment of ADHD in Youths With Limited Response to Standard Doses

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ABSTRACT

Objective:

To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD).

Method:

Two randomized, double-blind trials of atomoxetine nonresponders ages 6 to 16 years were conducted comparing continued treatment with same-dose atomoxetine to treatment using greater than standard efficacious doses (study 1: up to 3.0 mg · kg−1 · day−1; study 2: up to 2.4 mg · kg−1 · day−1).

Results:

The primary outcome measure for both studies was mean ADHD Rating Scale (ADHD RS) total score. For study 1 (N = 122), decreases in ADHD RS total scores were not significantly different between treatment groups (mean change [SD]: continued same dose, −8.9 [11.2]; high dose, −9.8 [13.1]; p = .595). Likewise, for study 2 (N = 125), treatment groups did not differ (mean change [SD]: continued same dose, −6.2 [12.2]; high dose, −8.9 [10.0], p =.110). Tolerability was not significantly different between the continued same-dose and high-dose groups.

Conclusions:

These studies provide evidence that current dose recommendations are appropriate for most patients, suggesting no systematic advantage to increasing atomoxetine doses beyond current guidelines. In both studies, continued treatment, whether at a higher dose or the previous dose, was associated with improved outcomes in patients who demonstrated incomplete/inadequate response to acute ADHD treatment, although without a placebo arm, we cannot rule out the possibility that expectancy played a role in symptom improvement.

Section snippets

Participants

Patients were children and adolescents ages 6 to 16 years who met DSM-IV diagnostic criteria for ADHD (any subtype). For inclusion in either study, scores on the ADHD RS had to be at least 1.5 SDs above the norms for age and sex. Patients with bipolar disorder, a psychotic illness, seizures, pervasive developmental disorder, or taking concomitant psychoactive medications were excluded. Patients who, in the investigator's opinion, were considered to be at serious suicidal risk or were likely to

Study 1

Of the 516 patients who were randomly assigned in the initial comparator study (459 of these received atomoxetine during the original comparison or were later switched to atomoxetine), 122 were classified as atomoxetine nonresponders after 6 to 8 weeks of treatment and randomly assigned to continue receiving their same dose (0.8-1.8 mg · kg−1 · day−1, n = 62, continued same dose) or a higher dose (up to 3.0 mg · kg−1 · day−1, n = 60, high dose). Patient demographics and characteristics (Table 2

DISCUSSION

Clinical trials have shown atomoxetine to be superior to placebo for the treatment of ADHD and well tolerated at the doses studied. There has, however, been some speculation about the possible benefit of increasing the dose for those patients who do not fully respond to the normal dose range. Data from the studies presented here provide evidence that the current dose recommendations are appropriate for most patients and suggest that there is generally no systematic advantage to increasing the

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Cited by (0)

The research was funded by Eli Lilly & Co. The Atomoxetine High-Dose Study Group consists of Charles E. Bailey, M.D., Charles D. Casat, M.D., David W. Dunn, M.D., Rosben L. Gutierrez, M.D., Robert B. Lehman, M.D., Peter D. Londborg, M.D., Michel Maziade, M.D., Raun D. Melmed, M.D., Marino Molina, M.D., Donna Palumbo, Ph.D., Humberto Quintana, M.D., Shannon K. Robinson, M.D., R. Bart Sangal, M.D., Elias H. Sarkis, M.D., Leslie V. Taylor, M.D., and Paul K. Winner, M.D.

Disclosure: Dr. Kratochvil has received grants for research support from Eli Lilly, GlaxoSmithKline, Cephalon, and McNeil; is a consultant for Eli Lilly, Organon, AstraZeneca, and Pfizer; and is on the speakers' bureau of Eli Lilly. Dr. Newcorn has received grants for research support from Eli Lilly, McNeil, and Shire, is a consultant to Eli Lilly, Novartis, and Celltech, a member of the advisory boards of Eli Lilly, McNeil, Novartis, Shire, Celltech, Cephalon, and Sanofi-Aventis, and a speaker for Eli Lilly, McNeil, Novartis, Shire, and Cephalon. Dr. Saylor has received research support from Eli Lilly, Cephalon, Shire, Bristol-Myers Squibb, Otsuka, New River, and Forest and is on the speakers' bureau of Eli Lilly. Dr. Busner has received grants for research support from Eli Lilly, Bristol-Myers Squibb, Merck, and Shire and has served on the speakers' bureaus or has been a consultant to Bristol-Myers Squibb, Eli Lilly, and Shire. Dr. Luber receives research support from Sanofi-Pasteur, Merck, GlaxoSmithKline, Eli Lilly, Targacept, and Abbott, is on the speakers' bureaus of GlaxoSmithKline, Sanofi Pasteur, Eli Lilly, Shire, McNeill, Abbott, and Roche, and is a member of the advisory panels of Eli Lilly, Roche, McNeill, and Merck. Dr. Turgay has received research and educational grants from Eli Lilly, Janssen Ortho, Janssen Cilag, Celltech, AstraZeneca, Novartis, Purdue Pharma, TV Ontario, The Hospital for Sick Children, University of Ottawa, Wellesley Foundation, The Scarborough Hospital Foundation, Children's Hospital of Eastern Ontario Foundation, Canadian Counseling Association, and Nestlé. Dr. Weiss has received grants for research support from Eli Lilly and a consultant to and on the speakers' bureaus of Novartis, Shire, Purdue, Jansen, and Eli Lilly. Drs. Allen, Dickson, Michelson, Moore, and Ruff and Ms. Ramsey are employees and shareholders of Eli Lilly. Ms. Vaughn has no financial relationships to disclose.

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