Priapism is defined as a prolonged erection lasting for at least four hours in the absence of stimulation, resulting in significant pain and ischemia. It can result in permanent erectile dysfunction if not promptly treated. Priapism is a rare adverse effect that has been reported with many antipsychotics including chlorpromazine, quetiapine, risperidone, ziprasidone, aripiprazole, and clozapine (Andersohn et al. 2010). The proposed mechanism for priapism is related to clozapine’s alpha1-adrenargic antagonism. Priapism generally occurs early in the course of clozapine treatment or after a dose increase, but was reported in one case 11 years after the onset of clozapine treatment (Raja and Azzoni 2006). The exact incidence of priapism due to clozapine is not currently known, as much of the published literature is from case reports, case series, and spontaneous, voluntary reports of adverse drug reactions found in databases. For example, six cases of clozapine-induced priapism were reported to the US Adverse Event Reporting System from 2004-2007 (Andersohn et al. 2010).
Initial treatment includes corporal aspiration often with saline irrigation, corporal injection of sympathomimetics (usually phenylephrine), and surgical management if the previous steps were unsuccessful (Levey, Segal, and Bivalacqua 2014; Shigehara and Namiki 2016). It is generally recommended to discontinue clozapine in the acute setting when it is presumed to be the cause. There are several reports of successful rechallenge in the literature (de Nesnera 2003; Raja and Azzoni 2006; Kashyap et al. 2013), but there are other reports of recurrence even after slow titrations (Kashyap et al. 2013; Donizete da Costa, Toledo da Silva Antonialli, and Dalgalarrondo 2015). One patient with recurrent clozapine-induced priapism was successfully treated with ongoing goserelin acetate injections (Kashyap et al. 2013).