Dapoxetine (Priligy)

Detailed overview

Dapoxetine is a serotonin reuptake inhibitor but not an antidepressant in the usual sense. What separates it from the rest of the class is pharmacokinetics: it absorbs quickly, peaks quickly and clears quickly. That is what allows on-demand dosing 1-3 hours before intercourse, in contrast to the weeks of daily dosing typical of SSRIs. The mechanism rests on the role of serotonin in the ejaculatory reflex: raising synaptic serotonin delays the reflex threshold being reached. This has long been known, and SSRIs were used off-label for this purpose before. Dapoxetine's novelty is not the effect but the dosing pattern. Efficacy has been confirmed by several meta-analyses. Li 2014, Li 2018 and the Zhao 2019 systematic review all found that dapoxetine significantly increases intravaginal ejaculatory latency time and improves patient satisfaction versus placebo. The improvement is real but not dramatic; the effect is dose-dependent, and so are the adverse effects. The key safety issue is orthostatic syncope. Modi 2009 characterised the pharmacokinetic and ECG profile in detail; because of the propensity to syncope the tablet should be taken with plenty of water, alcohol avoided, and the drug omitted entirely in significant cardiac disease. It was not approved in the United States although it was in Europe, and that divergence alone signals that the benefit-risk judgement was not clear-cut.