Spontaneous ejaculation with the use of noradrenergic reuptake inhibitors

Abstract

The Netherlands Pharmacovigilance Centre Lareb maintainsthe spontaneous adverse drug reaction (ADR) reportingsystem in the Netherlands. The primary aim of this systemis to detect ADRs that were not identified prior to drugmarketing [1]. Physicians, pharmacists, and patients canreport suspected ADRs to the pharmacovigilance centre.We describe three case reports of spontaneous ejaculation,without sexual arousal, after micturition associated with theuse the noradrenergic reuptake inhibitors methylphenidate,atomoxetine, and venlafaxine reported by Lareb betweenJanuary 1996 and December 2011.Thefirstreport,fromapsychiatrist.concernsa40-year-oldman who received atomoxetine. After 3 weeks, the patientdeveloped spontaneous ejaculations following micturitionurgency up to eight times a day without sexual arousal. Thepatientrecoveredafterwithdrawalofatomoxetine.Thepatientpreviously used dexamphetamine, which also gave spontane-ous ejaculations. He recovered upon cessation of dexamphet-amine. Concomitant medication is not reported.The second report, from a consumer, concerns a 25-year-old man who experienced spontaneous ejaculation withoutsexual arousal following testicular pain after micturitionwith the use of methylphenidate. The use of concomitantmedication was not reported. Past drug therapy includedatomoxetine, which also gave spontaneous ejaculations fol-lowing micturition.After 2years, thepatientuses mainlythelong-acting variant of methylphenidate (Concerta®) andsometimes the shorter-acting variant of methylphenidate(Ritalin®). Although spontaneous ejaculations are still pres-ent, they are less frequent with this drug regimen.The third report, from a psychiatrist, concerns a 60-year-old man who experienced spontaneous ejaculations withoutsexual arousal one to two times a week within a day aftercommencing venlafaxine for depression. The ADR wors-ened after a dose increase from 225 to 375 mg. The outcomeof this report is unknown.In the literature, there are two case reports of spontaneousejaculation with sexual arousal with the use of reboxetine.Both patients recovered within 2 weeks of reboxetinewithdrawal [2, 3]. Case reports concerning spontaneousejaculation without sexual arousal with the use of othernoradrenergic reuptake inhibitors were described with theuse of milnacipran [4], zotepine [5], and nefazodone [6].Spontaneous ejaculation occurred after micturition [6] anddefecation [4], with a frequency varying from once per 2 or3weeks[4] to several [5] to seven times daily [6]. Allpatients recovered after drug withdrawal [4–6].The exact mechanism of spontaneous ejaculation is un-known. Ejaculation is controlled by both the sympathic andparasympathic system and consists of an emission and expul-sion phase [3]. Ejaculation latency time is regulated by thesympathic system. Hypothetically, by reducing ejaculatory la-tency time, spontaneous ejaculation can occur [3]. Adrenergicdrugs are sometimes used as treatment for delayed ejaculation[3].Inrats,ejaculationwasinducedbysystemicadministrationofamphetamine[7].Also,stimulationofnoradrenaline(rebox-etine [2], milnacipran [4]), and 5-hydroxytryptamine (5-HT2)antagonists (nefazodone) [6] could lead to decreased ejacula-tion latency time. On the other hand, selective serotonin reup-take inhibitors (SSRIs) [3, 4] and 5-HT1a antagonists couldlead to increased ejaculation latency time [2, 3].