Tolerability and safety of reboxetine

Reboxetine is a selective noradrenaline reuptake inhibitor which has been f ound to be effective in the treatment of depression. Reboxetine has little effect on 5-HT or dopamine reuptake, does not inhibit monoamine oxidase act ivity, and demonstrates low affinity for alpha-adrenergic, muscarinic and h istaminergic receptors. The pharmacological profile is such that many of th e 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 genera lly well tolerated; the rate of discontinuation due to adverse events was s imilar to that with placebo. Although dry mouth, constipation and increased sweating were all significantly more frequent with reboxetine than with pl acebo, they were less common than with imipramine or desipramine. The frequ ency of adverse events was similar to that seen with fluoxetine. The profil e of adverse events seen in clinical trials is reflected in clinical practi ce. Urinary hesitancy with reboxetine treatment has been reported in 4-12% of patients, and the drug should generally not be prescribed to men with pr ostatomegaly, or only under close supervision. There is no reported interac tion 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 re boxetine in clinical trials, although symptoms related to hypotension or ta chycardia may be experienced by up to 10% of patients; the drug should be u sed cautiously in patients with cardiac disease and those taking antihypert ensives. Suicide attempts were infrequent in clinical trials, and occurred less often than with placebo, fluoxetine or imipramine. No deaths or seriou s sequelae following reboxetine overdose have been described. Studies in an imal models indicate that reboxetine has low toxicity, but the effects of t reatment during human pregnancy are unknown.