High-dose atomoxetine treatment of ADHD in youths with limited response to standard doses.
OBJECTIVE
To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD).


METHODS
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 . day; study 2: up to 2.4 mg . kg . day).


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.
Kratochvil
Christopher J
CJ
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.. Electronic address: ckratoch@unmc.edu.
Michelson
David
D
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Newcorn
Jeffrey H
JH
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Weiss
Margaret D
MD
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Busner
Joan
J
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Moore
Rodney J
RJ
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Ruff
Dustin D
DD
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Ramsey
Janet
J
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Dickson
Ruth
R
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Turgay
Atilla
A
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Saylor
Keith E
KE
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Luber
Stephen
S
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Vaughan
Brigette
B
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Allen
Albert J
AJ
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
Dr. Kratochvil and Ms. Vaughan are with The University of Nebraska Medical Center, Omaha; Dr. Newcorn is with Mount Sinai Medical Center, New York; Dr. Weiss is with The Children's and Women's Health Centre of British Colombia, University of British Colombia, Vancouver; Dr. Busner is with the Pennsylvania State College of Medicine, Hershey, and PharmaStar, Wayne, PA; Dr. Turgay is with the University of Toronto, Scarborough, Ontario; Dr. Saylor is with NeuroScience, Inc., Herndon, VA; Dr. Luber is with the Rockwood Clinic, Spokane, WA, and the University of Washington Medical School, Seattle; Ms. Ramsey and Drs. Michelson, Moore, Ruff, and Allen are with the Eli Lilly Research Laboratories, Indianapolis; Dr. Dickson is with Eli Lilly Canada, Toronto.
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D011437:Propylamines / Q000008:administration & dosage* / Q000627:therapeutic use
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride