Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Strattera (Eli Lilly)
10 mg, 18 mg, 25 mg, 40 mg and 60 mg capsules
Approved indication: attention deficit hyperactivity disorder
Australian Medicines Handbook section 18.5
Controversy surrounds the diagnosis of attention deficit hyperactivity disorder and its treatment with stimulant drugs(see Aust Prescr 1995;18:60-3 and Aust Prescr 1995;18:64). Prescribers now have the option of treating patients with atomoxetine, a non-stimulant drug.
Atomoxetine inhibits the reuptake of noradrenaline by presynaptic neurons, but it is uncertain if this explains the therapeutic effects. The drug is well absorbed, but its bioavailability varies with each patient's oxidative metabolism. The bioavailability is higher in patients with reduced metabolism and their plasma concentrations of atomoxetine are also higher because metabolic clearance is reduced. As the metabolism of atomoxetine involves cytochrome P450 2D6 there is a potential for interactions with other drugs metabolised by this enzyme system. The half-life of atomoxetine is 5.2 hours, but this increases to 21.6 in poor metabolisers. Most of the metabolites are excreted in the urine.
A placebo-controlled dose-response study titrated twice-daily doses of atomoxetine at weekly intervals in 297 children. It found that, after eight weeks, a total daily dose of 1.2 mg/kg improved the children's symptoms on a variety of rating scales. This dose reduced the score on the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) by 13.6, from a baseline score of 39.2, while placebo achieved a reduction of 5.8 from a baseline score of 38.3. 1
Another trial compared once-daily doses with placebo for six weeks in 171 children. Atomoxetine reduced the mean score on the ADHD RS by 12.8 from a baseline of 37.6, while placebo reduced the score by 5.0 from a baseline of 36.7. This suggests single daily doses have similar efficacy to divided doses. 2
Atomoxetine has been compared with methylphenidate in a 10-week, randomised, open-label trial. In the 178 children who took atomoxetine, the ADHD RS score decreased from 39.4 to 20.0 while it decreased from 37.6 to 19.8 in the 40 children who took methylphenidate. 3
Atomoxetine is approved for use in children, over six years old, and adolescents, but it can also be used in adults. A small double-blind, crossover study found that a daily dose of 80 mg atomoxetine reduced the ADHD RS from 30 to 21.5 while a placebo had no effect. 4 Two larger randomised placebo-controlled trials showed that 10 weeks treatment with atomoxetine produced greater reductions in the investigators' ratings of the patients' condition. In the trial involving 280 adults, it reduced the total symptom score from 33.6 to 17.6 while placebo reduced it from 33.2 to 23.9. In the other trial (256 adults) atomoxetine reduced the mean score from 34.9 to 17.6 while placebo reduced it from 34.2 to 22.6. 5
Most of the trials were relatively short, so the long-term efficacy and safety is uncertain. Common complaints from children were abdominal pain and vomiting, while adults reported constipation, nausea, dry mouth and reduced appetite. Atomoxetine increases the pulse rate and blood pressure, but some patients will develop postural hypotension. In adults there may be urinary hesitancy or retention and atomoxetine can impair sexual function. As atomoxetine may affect growth, height and weight should be monitored during the treatment of children.
Atomoxetine has the advantage of not being a controlled drug and it does not appear to cause dependence. However, a therapeutic advantage over stimulants has not been shown.
