Although there are only a few reported cases of priapism with SSRIs, a proposed mechanism of action for this condition from antipsychotic therapy is from an alpha-1 adrenergic blockade in the corpora cavernosa of the penis, leading to arteriodilation causing increased blood flow into the corpora cavernosa that then inhibits the sympathetic system in its role of inducing detumescence. For SSRIs, priapism may be due to activity with 5-HT3 receptors but previous research has suggested that paroxetine may actually prevent formation of nitric oxide in the erectile process.

While such events are rare, it is important to convey to patients risks associated with SSRIs like paroxetine, as untreated priapism can lead to permanent penile damage without immediate care.

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