Tolerability and safety of reboxetine

Reboxetine is a selective noradrenaline reuptake inhibitor which has been found to be effective in the treatment of depression. Reboxetine has little effect on 5-HT or dopamine reuptake, does not inhibit monoamine oxidase activity, and demonstrates low affinity for alpha-adrenergic, muscarinic and histaminergic receptors. The pharmacological profile is such that many of the untoward effects of other antidepressants are avoided. The adverse-effect burden of reboxetine, as revealed by treatment studies, appears relatively benign. An analysis of data from over 2600 patients showed it to be generally well tolerated; the rate of discontinuation due to adverse events was similar to that with placebo. Although dry mouth, constipation and increased sweating were all significantly more frequent with reboxetine than with placebo, they were less common than with imipramine or desipramine. The frequency of adverse events was similar to that seen with fluoxetine. The profile of adverse events seen in clinical trials is reflected in clinical practice. Urinary hesitancy with reboxetine treatment has been reported in 4-12% of patients, and the drug should generally not be prescribed to men with prostatomegaly, or only under close supervision. There is no reported interaction between reboxetine and the principal cytochrome P450 isotypes, and so the risk of drug interactions appears low. Nevertheless, reboxetine should be used cautiously with drugs that are metabolized by, or potently inhibit, CYP3A4. Sustained effects on blood pressure have not been observed with reboxetine in clinical trials, although symptoms related to hypotension or tachycardia may be experienced by up to 10% of patients; the drug should be used cautiously in patients with cardiac disease and those taking antihypertensives. Suicide attempts were infrequent in clinical trials, and occurred less often than with placebo, fluoxetine or imipramine. No deaths or serious sequelae following reboxetine overdose have been described. Studies in animal models indicate that reboxetine has low toxicity, but the effects of treatment during human pregnancy are unknown.