Risperidone-Induced Priapism: A Case Report

To the Editor: Priapism is a prolonged, painful, and persistent penile erection usually not associated with sexual stimulation. Priapism results from an obstruction in the venous drainage of the corpora cavernosa of the penis sparing the glans penis and corpora spongiosa; thus, only the corpora cavernosa are turgid without affecting the other 2 components. It is this finding that distinguishes priapism from a normal penile erection.¹

Priapism is a relatively rare condition, but due to its potentially serious and long-term consequences and its potential as an adverse effect of many common medications, it is a matter of serious concern for clinicians. Impotence may occur in 50% of patients with an episode of priapism,² and it is considered a urologic emergency. We present a case of a patient who developed priapism during treatment with risperidone, an atypical antipsychotic medication, and the treatment decisions that followed.

Case report. Mr A, a 31-year-old African American man, had a 10-year history of schizophrenia, chronic, paranoid type, diagnosed using the DSM-IV criteria. The patient had been followed at our outpatient clinic since 1997 and had been compliant with the treatment recommendations. His symptoms of schizophrenia were under fairly good control with risperidone. There was no history of psychiatric inpatient hospitalization. The patient had never been married and had no children. He lived by himself and worked 1 day a week doing newspaper advertising inserts. He had been attending a community-based day program 1 day a week for 10 years. He was a high school graduate with some community college training in computers. The patient was a nonsmoker and a nondrinker and had no history of any illicit drug use. His medical history was significant for obesity, hypercholesterolemia, keloid on his neck, and tonsillectomy at age 6 years. His only medication was risperidone 2 mg in the morning and 3 mg at bedtime.

The patient presented to the emergency room in 2005 with a 10-day history of a persistent and painful penile erection. It was sudden in onset while the patient slept, and he awoke with a painful erection. The patient was not sexually active; there was no history of penile, genital, or pelvic trauma; and there was no evidence of any infection or malignancy. There was no change in his current medications and no reported use of any over-the-counter medication or any herbal preparation. The patient had a similar complaint 2 years earlier, but it resolved within a few hours and he did not seek medical care.

On this occasion, the erection persisted, and on the 10th day he presented to the emergency room. Routine laboratory tests were performed that included complete blood count, basic metabolic profile, and a coagulation study, and all the results were within normal limits. A diagnosis of priapism was made, and the urology service was consulted. They performed irrigation with normal saline followed by an injection of phenylephrine to the corpora cavernosa to reduce the priapism. There was some improvement in the patient's priapism, and he was transferred to the internal medicine floor. On the second day, his symptoms worsened, and he was offered a second phenylephrine injection, which he refused due to pain. He was then transferred to the operating room where a Winter shunt was placed between corpora cavernosa and corpora spongiosa to relieve his symptoms. His priapism resolved completely within a few hours with the shunt placement. Sickle cell anemia was a potential cause of his priapism, so a hematology consult was obtained. In the absence of any history of anemia, pain crisis, or blood transfusion, a diagnosis of sickle cell anemia was considered unlikely and was ruled out by testing, but the patient was found to be a carrier. While in the hospital, his risperidone treatment was continued. The patient was discharged to home on the fourth day to be followed up in our outpatient psychiatry clinic. Risperidone was the only known causative factor, and despite its efficacy for this patient, it was discontinued. The patient's treatment was changed to aripiprazole in a cross-tapering manner over 3 weeks. The priapism had not returned when the patient was followed up 2 months later.

Although priapism can occur in all age groups, it occurs more frequently in the third and fourth decades, often early in the morning, and is noticed on waking.³ The cause is unknown 50% of the time, and the rate of recurrence is 30%–40%.³ The exact pathophysiology is still unclear, and it is considered to be multifactorial in origin. However, among all the reported cases of priapism, 15%–26% are linked to the use of antipsychotic medications.⁴ Priapism may occur at any time during the treatment course of psychotropic medications and may occur even without a change in the medication dosage.⁵

Priapism is a result of an obstruction in the venous drainage from the corpora cavernosa of the penis. Priapism is commonly divided into 2 subtypes,⁶ high-flow and low-flow priapism. High-flow subtype results from a rupture of a cavernous artery that leads to an abnormal blood flow in the penis. This condition is rare and is usually painless due to lack of ischemia, has a favorable prognosis, and is generally not considered a true emergency.⁷

In low-flow priapism, there is a reduction or absence of the venous drainage from the emissary venules, which results in hypoxia, acidosis, and ischemia. This subtype is painful, accounts for the majority of the cases, and can lead to irreversible fibrosis of the cavernosal spaces if not treated urgently.⁷ Low-flow priapism is associated with the use of antipsychotic medications. The exact mechanism underlying antipsychotic-induced priapism is still unclear and is considered multifactorial in origin.⁷ The histaminic system⁸ and hypersensitization of the β-adrenergic receptors⁹ have been proposed as important influences in this phenomenon.

The commonly proposed mechanism of antipsychotic-induced priapism is related to the α-adrenergic system. Arterioles in the penis that supply blood to the corpora cavernosa are in a tonic state of contraction during the flaccid state of penis, a condition mediated by the α-adrenergic activity.¹⁰ During erection, there is a relaxation of the cavernous and the arteriolar smooth muscle leading to an increase in the blood flow into the sinusoidal spaces.¹¹ Priapism is proposed to be mediated by α receptors located in the corpora cavernosa of the penis,⁸ and the α-adrenergic antagonist properties found in many psychotropic medications¹² could very well explain the mechanism underlying priapism induced by these medications. It has also been proposed that the corpora cavernosa in some men are exceptionally sensitive to α-blocking agents.^8,13

Several other causes of priapism include perineal trauma, some antihypertensives, phosphodiesterase type 5 inhibitors, other behavior medications (trazodone), anticoagulants, and hematologic disorders including sickle cell anemia, leukemia, lymphoma, and thrombocytopenia.⁷ However, the only medication our patient was taking was risperidone, which is known to possess α₁- and α₂-adrenergic antagonist properties,¹⁴ and as there was no indication of any other medical illness or causative factor, we propose his condition of priapism to be related to the use of risperidone.

Priapism is a urologic emergency, and treatments, including ice packs, enemas, medications, and anesthesia, generally do not produce consistent results.¹⁵

Management usually includes intracavernous injection of an α-adrenergic agonist.⁷ This patient needed to be maintained on an antipsychotic regimen, which posed a particular problem given the high degree of risk for priapism with these medications. At the time of our patient's follow-up, the only medication not reported to be associated with priapism was aripiprazole.