Atomoxetine (Strattera):

Atomoxetine is a new drug being heavily promoted for ADHD by Lilly Pharmaceuticals.  It blocks the pre-synaptic norepinepherine transporter, effectively increasing the norepinepherine effect.  It is somewhat effective and appears to being widely used.  However, it is very expensive costing $135 to $270 per month for 6-12 mg/day.  

Many of the studies are poor quality studies done by the manufacturer with their hand-picked, favorite researchers from Harvard and elsewhere.  The studies were carefully designed to make atomoxetine look good.  In fact, I have seen many families discontinue the drug due to inadequate benefit and side-effects more common than reported in the manufacturer studies.  Consultant for The Medical Letter report the same experience.

Atomoxetine is unlikely that it is any better than nortriptyline, a fairly similar drug also found effective for ADHD which is available as a generic for around $13 per month.  In fact, one expert has recently published an analysis of the research concluding that atomoxetine is inferior to desipramine, an anti-depressant very similar to nortriptyline (J Psychopharmacol. 2003 Sep;17(3):332-6).

The Medical Letter claims that stimulants are better.  However, I think that people engage in a lot of wishful thinking on stimulants.  The large majority of psychiatrists, teachers, parents, and ADHD children thinks it helps them do better in school.  Unfortunately, controlled research has found this not to be true.  Stimulants feel better, but aren't better.  Non-pharmacological meaning covered on this website should be used first.  People should be much more reluctant to give psychoactive drugs to children.  Still, atomoxetine might be worth a try after several other approaches have failed.

Lilly’s NE transporter inhibitor, Atomoxetine (Strattera). A selective NE reuptake inhibitor. Side-effects abdominal discomfort, decreased appetite (which may translate over the long term into weight loss), dizziness, vertigo, irritability, and mood swings. Metabolized by CPY2D6 so fluoxetine, paroxetine, quinidine may increase blood levels & avoid full dose unless needed. Lilly study= Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW. Neuropsychopharmacology 2002 Nov;27(5):699-711. Atomoxetine-induced increase of catecholamines in Pre-Frontal Cortex, a region involved in attention and memory, mediates the therapeutic effects of atomoxetine in ADHD. In contrast to methylphenidate, atomoxetine did not increase DA in striatum or nucleus accumbens, suggesting it would not have motoric or drug abuse liabilities. Rapidly & completely absorbed. Half-life 5 hr. although the 5-10% of people with polymorphism of CYP2D6 have 24 hour half-lives. With CYP2D6 inhibitors paroxetine, fluoxetine, and quinidine, keep at initial dose unless no improvement in 4 weeks. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ, Kelsey D, Wernicke J, Dietrich A, Milton D.

Higher Dose Atomoxetine (Strattera) if ADHD Youth has ODD as well: In a large 8-week DB PC study of 293 children ages 8-18 with ADHD with (39%) or without (61%) oppositional defiant disorder (ODD), atomoxetine (0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) was given. Both groups showed similar improvement, but those with ADHD plus ODD needed 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD showed improvement at 1.2 mg/kg/day and extra benefit at 1.8 mg/kg/day. Atomoxetine Treatment in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder. Newcorn JH, Spencer TJ, et al. Mount Sinai, Massachusetts General, and Eli Lilly drug company. J Am Acad Child Adolesc Psychiatry. 2005 Mar;44(3):240-248. Ed: It is sad to see drug companies employees working so closely with academic researchers in studies being funded by the drug companies.  The opportunities for influencing the reported results are vast. 

Academic Benefit Not Found in Small Study: In a DB PC study of 153 ADHD children (age 8 to 12 years), there were significant improvements both for parent and teacher ratings of behavior for children receiving atomoxetine therapy. However, no significant effects were revealed for the teacher ratings of academic productivity. Atomoxetine in the management of children with ADHD: effects on quality of life and school functioning. Brown RT, et al. Temple University. Clin Pediatr (Phila.) 2006 Nov;45(9):819-27.

One Daily Atomoxetine (Strattera) Better than Placebo for ADHD: In an 8-week DB PC study of 197 children, 6 to 12 years of age, with ADHD, atomoxetine or placebo were given once daily in the mornings. The atomoxetine group did better than the placebo group in both the morning and evening assessments although the abstract did not report the degree of benefit. Once-Daily Atomoxetine Treatment for Children With Attention-Deficit/Hyperactivity Disorder, Including an Assessment of Evening and Morning Behavior: A Double-Blind, Placebo-Controlled Trial. Kelsey DK, Sumner CR, Casat CD, Coury DL, Quintana H, Saylor KE, Sutton VK, Gonzales J, Malcolm SK, Schuh KJ, Allen AJ. Lilly Drugs; Children's Hospital, Columbus, Ohio; Louisiana State University; NeuroScience, Bethesda, Maryland. Pediatrics. 2004 Jul;114(1):E1-E8. Ed: Strattera has been a disappointment for many physicians and families. Nortriptyline or stimulants work better. 

Atomoxetine Better than Sugar Pills for ADHD in Poor Quality Study: 416 ADHD children and adolescents who responded during a 12-week, open-label trial of atomoxetine were randomized to atomoxetine or placebo for 9 months in a DB study. At the end, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 22.3%, placebo 37.9%, p =.002. The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (28.4% vs. 47.6%, p <.001). Relapse Prevention in Pediatric Patients With ADHD Treated With Atomoxetine: A Randomized, Double-Blind, Placebo-Controlled Study. Michelson D, Faries DE, Zhang S = Lilly Research Laboratories, Buitelaar JK = University Medical Center, Nijmegen, The Netherlands; Danckaerts M = Leuven, Belgium; Gillberg C = Barnneuropsykiatriska Kliniken, Goteborg, Sweden; Spencer TJ, Biederman J = Massachusetts General; Zuddas A = Clinica di Neuropsichiatria Infantile, Universita' di Cagliari, Cagliari, Italy. J Am Acad Child Adolesc Psychiatry. 2004 Jul;43(7):896-904. Ed: This is a poor quality study run by the manufacturer Lilly with its usual array of academic psychiatrists who make their living doing studies for drug companies. The issue with ADHD is not whether to continue a medication or switch to sugar pills, but whether to start and continue one medication as compared to another.  Atomoxetine has proven disappointing for most families who have tried it despite its high cost. Nortriptyline is a better initial choice as a non-stimulant, but Lilly knows its easier to beat a sugar pill, especially when limiting your study to only those who improved while on atomoxetine in the first place.

Atomoxetine Helps Child ADHD, Compared to Methylphenidate: Two DB PC studies 291 patients. The half that were naive to stimulants put on atomoxetine, methylphenidate or placebo. The other half just on atomoxetine or placebo. In both, atomoxetine highly significant over placebo on ADHD RS.  Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. Spencer T, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ. J Clin Psychiatry 2002 Dec;63(12):1140-7; MGH

Atomoxetine Helps Girls’ ADHD: DB PC 291 7-13 yo girls. One dropout each group. MGH. Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder. Biederman J, Heiligenstein JH, Faries DE, Galil N, Dittmann R, Emslie GJ, Kratochvil CJ, Laws HF, Schuh KJ; Atomoxetine ADHD Study Group. Pediatrics 2002 Dec;110(6):e75

Atomoxetine QD as good as BID in Children: DB PC for 6 week with 171 6-16yos. Effect size 0.71. Similar to studies with BID. 3% dropouts. Benefits seemed to last. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Michelson D, Allen AJ, et al. Am J Psychiatry 2002 Nov;159(11):1896-901

Atomoxetine as good as Methylphenidate in Children: 229 ADHD kids, randomized open study 10 weeks. 44 on methylphenidate. No difference in improvement with 48% vs. 44% decrease in symptoms. 5% vs. 11% side-effect dropout. Good for both inattentiveness and hyper/impulsiveness. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. Kratochvil CJ, Heiligenstein JH, Dittmann R, Spencer TJ, Biederman J, Wernicke J, Newcorn JH, Casat C, Milton D, Michelson D. Univ Nebraska. J Am Acad Child Adolesc Psychiatry 2002 Jul;41(7):776-84. Ed: This is a very poor quality Harvard-Lilly study. Open trials are very prone to fudging.  Why a double-blind methodology was not used is beyond me.  Maybe, they wanted to make sure that atomoxetine didn't do too badly. After all, there are hundreds of millions in profits riding on the results. 

Methylphenidate More Effective: Two 3-week DB PC studies by stimulant manufacturers found atomoxetine less effective than methylphenidate (Concerta) or amphetamines (Adderall XR) (SB Wigal et al, presented at the annual meeting of the American Psychiatric Association; New York, June 2004; JE Kemner et al, presented at the annual meeting of the Collegium Internationale Neuro-Psychopharmacologicum; Paris, June 2004).

Atomoxetine 1.2mg/kg as good as1.8mg/kg in Children: DB PC 0.5, 1.2, 1.8mg/kg/d vs. placebo. 297 8-18-year-olds with ADHD, 71% mixed. 8 week. 38% also oppositional defiant disorder. Family and social functioning improved. 5% dropout from side-effects. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Michelson D, Faries D, et al. Atomoxetine ADHD Study Group. Pediatrics 2001 Nov;108(5):E83; Indiana Univ & Lilly

Atomoxetine Helped Adult ADHD in 2 Large DB: Two large DB PC studies by Eli Lilly drug company of 280 and 256 adult ADHD patients for 10 weeks each reported that both studies found benefits from atomoxetine with drop-outs from side-effects of less than 10%. Improvement measured by Connor's Adult ADHD Rating Scale. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Michelson D, Adler L, et al. Biol Psychiatry. 2003 Jan 15;53(2):112-20

No Withdrawal Syndrome: In four Eli Lilly DB PC studies for 9 to 10 weeks, there was no evidence of any withdrawal side-effects from abruptly stopping atomoxetine. Changes in symptoms and adverse events after discontinuation of atomoxetine in children and adults with attention deficit/hyperactivity disorder: a prospective, placebo-controlled assessment. Wernicke JF, Adler L, et al. J Clin Psychopharmacol. 2004 Feb;24(1):30-5.