Where Does Strattera Fit into the Treatment of ADHD? - How Strattera Works?

Written by Carol Watkins, M.D.

In December 2004, Lilly Pharmaceuticals announced that it was adding a warning about atomoxetine (Strattera) and hepatitis. Two cases of severe hepatitis were reported associated with the use of this medication. Both cases resolved after the medication was stopped. Patients should contact their physician if they notice signs of possible hepatitis: Dark urine, yellowing of skin or eyes, or upper abdominal pain. It should be noted that only 2 cases have been reported and over 2 million people have taken atomoxetine.

How Strong and How Fast?

Stimulants start to work in less than an hour. Because of this, one can rapidly determine the best dose. Atomoxetine has a more subtle, gradual onset. One must increase the dose over several days or weeks. One may not see the maximum effect of a given dose for about three weeks. In some cases, I may do a cross over in which the individual takes a lower dose of the stimulant while waiting for the atomoxetine to take its full effect. Limited studies have suggested that atomoxetine is equally effective to methylphenidate (Ritalin) for a variety of AD/HD symptoms. (2) In my own experience, this is not always true. Some individuals experience even the highest recommended doses of the drug as less effective than the conventional stimulants.

Atomoxetine is metabolized through the cytochrome P-450 2D6 pathway. However the major metabolite is also active. The activity of the CYP 2D6 system can vary widely in perfectly healthy people. Individuals who metabolize it slowly will build up a higher level faster than those who metabolize it rapidly. Because of this, we may not be able to achieve an effective dose in some individuals within the FDA dosage guidelines. Fluoxetine (Prozac) and Paroxetine (Paxil), as well as other drugs affect the metabolism of atomoxetine. If one is taking atomoxetine it is important to check with the doctor or pharmacist to make sure that the atomoxetine does not interfere with other medications that the individual is taking.

Strattera: A Double Edged Sword?

Some of the advantages of Strattera may be a double edged sword. Its lower abuse potential might make us more willing to prescribe it for individuals with a substance abuse problem. Its weak antidepressant effect might make us more comfortable prescribing it for individuals who might have co-morbid depression. However this should not relieve clinicians from the responsibility for assessing and treating co-morbid substance abuse and mood problems. Atomoxetine is more convenient because you can call in refills. However, one of the major reasons for failure for AD/HD medication treatment failure is inadequate follow up with infrequent dosage monitoring and adjustments. Medication management visits can be therapeutic. Frequent visits also help pick up changes in the patient's clinical condition.

So, Where Does Strattera Fit In?

I still recommend the stimulants as the first-line drugs for AD/HD. They have stood the test of time. We are familiar with their strengths and their side effects. Their quick onset enables the clinician to more rapidly adjust the dose. The stimulants—even the newer ones—are less expensive than atomoxetine. I have found a number of patients who feel that even the higher doses of atomoxetine are not as effective as the stimulants. However there are many people who do not respond to stimulants or who cannot tolerate the side effects. I have achieved excellent results in a number of individuals who felt jumpy or irritable on stimulants. For these people, atomoxetine can be an excellent medication.

About the author: Carol Watkins, M.D. is Board Certified in Child, Adolescent & Adult Psychiatry and in private practice in Baltimore, MD.

Sources:

1. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 2002; 27:699-711.
2. Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: A prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 2002;41:776-84.
3. Biederman, J, WIlens, T, Mick, E, Spencer, T, Faraone, SV, Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder Reduces Risk for Substance Use Disorder, Pediatrics, 104:2 1999 pe20.
4. Michelson D, Adler I, Spencer T, et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry 2003;53:112-20.
5. Michelson, D, Faries, D, Wernicke, J, Kelsey, D, Kendrick, K, Sallee, FR, Spencer, T., Atomoxetine in the Treatment of Children and Adolescents with Attention-Deficit Disorder: A Randomized, Placebo-Controlled, Dose-Response Study, Pediatrics 2001, 108:5.

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