Dapoxetine. Premature ejaculation: not worth the risk

Time until ejaculation during sexual intercourse is highly variable. Some men and their partners find sex unsatisfactory because they feel ejaculation occurs too quickly. Psychobehavioural therapy is the first option. Dapoxetine, a short-acting serotonin reuptake inhibitor, is the first drug to be authorised for use in premature ejaculation in some EU member states. Four double-blind randomised placebo-controlled trials in a total of 4414 men are available. At best, only one in three men and one in five women perceived at least a moderate improvement in sexual satisfaction through a specific effect of dapoxetine. A substantial placebo effect was observed in one-third of participants of both sexes. Dapoxetine exposes men to the numerous adverse effects of all serotonin reuptake inhibitors, some of which can be severe, such as self-harm, aggressive behaviour, and serotonin syndrome. Postural hypotension and syncope can also occur. Dapoxetine is strongly metabolised by the cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6, and thus carries a risk of numerous pharmacokinetic interactions. In practice, there is no justification for exposing men to potentially serious adverse effects for only a moderate symptomatic improvement in a poorly defined disorder. Behavioural approaches should remain the cornerstone of therapy.