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.
4 mg tablets
Approved indication: major depression
Australian Medicines Handbook section 18.1
Reboxetine inhibits the reuptake of noradrenaline, but has little effect on the reuptake of serotonin or dopamine. This gives it a relatively selective mechanism of action on neurotransmission. The resulting increased concentration of noradrenaline in synapses may help some patients with depression.
Although short-term studies show that reboxetine improves depression more than a placebo, the difference is not always statistically significant. An eight-week study of 347 elderly patients found that reboxetine had similar efficacy to imipramine.1 Another eight-week study of 168 patients showed no significant differences in the overall efficacy between reboxetine and fluoxetine.2
A multi centre study investigated what happened to 283 patients during longer-term treatment. Patients who had responded to six weeks' treatment with reboxetine, were randomised to continue therapy or switch to a placebo. After 46 weeks56% of the patients switched to placebo had relapsed compared with only 22%of those who continued reboxetine.3
Doses of reboxetine are rapidly absorbed. The half-life is 13 hours and a steady state is reached within five days. If there has been no response to the starting dose, it can be increased after three weeks. A lower starting dose is recommended in the elderly. Lower doses are also appropriate for patients with renal or hepatic impairment as the drug is eliminated in the urine and by metabolism.
The metabolism of reboxetine involves cytochrome P450 (CYP3A4). Inhibitors of this enzyme, for example ketoconazole, will increase plasma concentrations of reboxetine.
In the comparison with imipramine, adverse events occurred in 68% of the patients taking reboxetine and 71% of those taking impramine.1 Comparison of reboxetine and fluoxetine shows that adverse events occur in approximately 67% of patients taking either drug.2 The adverse effects of reboxetine include dry mouth, constipation, insomnia, dizziness and tachycardia. ECG changes appear in 15% of elderly patients taking reboxetine. Hypotension can occur, but is less likely than in patients taking imipramine.1
Prescribers should be cautious about prescribing reboxetine to patients with glaucoma, prostatic hypertrophy/difficult micturition, cardiovascular disease or a history of seizures.
As depression often requires months of treatment, it would be reasonable to wait until more long-term safety data are available before prescribing reboxetine. A comparative study with venlafaxine, which inhibits the reuptake of serotonin as well as noradrenaline, would be informative.
- Katona C, Bercoff E, Chiu E, Tack P, Versiani M, Woelk H. Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial. J Affect Dis 1999;55:203-13.
- Massana J, Möller H-J, Burrows GD, Montenegro RM. Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder. Int Clin Psychopharmacol 1999;14:73-80.
- Versiani M, Mehilane L, Gaszner P, Arnoud-Castiglioni R. Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. J Clin Psychiatry 1999;60:400-6.