The Eli Lilly reps are almost delirious about their new ADHD “miracle drug”, Straterra (atomoxetine). This is not surprising. No pharmaceutical firm has survived the conversion of a blockbuster from brand to generic (as happened to Prozac in 2001) without sustaining a buyout or merger, and while it may be hard to drum up sympathy for a multi-billion dollar corporation, Eli Lilly is, in a sense, fighting for its life.

Not that Straterra is Lilly’s only potential lifesaver. Cymbalta, a dual reuptake inhibitor of norepinephrine and serotonin, is due out soon, and may end up dealing a drubbing to Effexor (venlafaxine). But that drama will have to wait for a future issue.

Straterra is probably the most carefully studied drug to date for ADHD because it was one of the first drugs to seek approval under a 1998 FDA guideline requiring stringent study procedures for drugs with primary pediatric indications. Thus, several large double-blind trials have been done, giving Straterra an immediate legitimacy that is rare for ADHD drugs.

The studies have recruited large numbers of people, including both children and adults, have been scrupulously designed, and have reported response rates from 52%-64%, depending on the study (1-3,5,6). All studies showed superiority over placebo. In most of the studies, dosing was b.i.d., with a maximum of 80-90 mg per day. Most of the studies were flexible dose designs, with the mean final dose varying from 1.3 mg/kg/day to 1.7 mg/kg/day. One fixed-dose study of children and adolescents (2) compared three doses: 0.5 mg/kg/day, 1.2 mg/kg/day, and 1.8 mg/kg/day. The two higher doses were equally effective, and so the recommended target dose in your PDR is 1.2 mg/kg/day.

Standard Straterra Dosing:

• Children: 0.5 mg/kg Q AM X 3 days, then 1.2 mg/kg Q AM


• Adults: 40 mg Q AM X 3 days, then 80 mg Q AM.

Nobody likes b.i.d. dosing if it can be avoided, and we have a nice Straterra study looking at this issue (3). In this study, 171 children and adolescents (ages 6- 16) were randomly assigned to receive either once-daily (in the morning) Straterra or Placebo. The average final Straterra dose was 1.3 mg/kg/day; this led to a response rate of 59.5%, significantly superior to placebo’s 31.3% response rate. Unfortunately, the gain in convenience leads to a side effect cost: rates of nausea, vomiting, and decreased appetite were 11.8%, 15.3%, and 20%, respectively, and all significantly higher than placebo. However, the authors report that most nausea was “transient and self-limiting.” Thus, it appears that you can get away with Q a.m. dosing of Straterra.

How does Straterra stack up against stimulants? There have been no double-blind comparisons published yet, which implies to TCR that Lilly isn’t particularly confident about the results of such head-to-heads. One open-label study compared Straterra with Ritalin in 228 children ages 7-15 (4). There was no placebo group in this study. Both groups improved equivalently on the standard ADHD rating scale; response rates were not reported. Aside from the lack of blinding and placebo, another problem with this study was that few patients were randomized to ritalin (40 assigned, only 25 completed) vs. Straterra (178 assigned, 118 completed). The question is whether a more robustly populated Ritalin arm might have led to treatment differences. We’ll never know.

Three studies have shown that Straterra works for adults with ADHD (5,6), by the way, though doses may need to be higher than the 1.2 mg/kg/day targeted in children.

Overall, Straterra seems in many ways to be a safe version of desipramine (DMI), another norepinephrine reuptake blocker that is effective in ADHD. Like DMI, Straterra is not a controlled substance and so can be called in and refilled endlessly. Also like DMI, it produces a response rate slightly below those usually reported for stimulants (60-70% vs. 70-80%), and the word on the street is that it works a bit more slowly than stimulants. Unlike DMI, though, there are no worrisome EKG changes with Straterra and hopefully there will be no reports of sudden death associated with its use.

A life-saver for Lilly? Unclear. But it will keep the boat afloat for a while longer.

TCR VERDICT:
Straterra Report Card

• Efficacy : B +


• Ease of Prescribing : A+

<sub>1. Spencer T, Heiligenstein JH, Biederman J, et al. Results from 2 proof-of concept, placebo-controlled studies of atomoxetine in children with attention- deficit/hyperactivity disorder. J Clin Psychiatry. 2002; 63:1140-1147.
2. Michelson D, Faries D, Wernicke J, et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: A randomized, placebo-controlled, dose-response study. Pediatrics. 2001;108(5):E83 (on-line version).
3. Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: A randomized, placebo-controlled study. Am J Psych. 2002; 159:1896-1901.
4. Kratochvil CJ, Heiligenstein JH, Dittman R. Atomoxetine and methylphenidate treatment in children with ADHD: A prospective, randomized, open-label trial. JAACAP. 2002; 41:776-784.
5. Spencer T, Biederman J, Wilens T, Prince J, et al. Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1998; 155:693-695.
6. Michelson D, Adler L, Spencer T, et. al. Atomoxetine in adults with ADHD: Two randomized, placebo-controlled studies. Biol Psychiatry. 2003; 53(2):112-120.</sub>