
==== Front
J Psychiatry Neurosci
J Psychiatry Neurosci
jpn
Journal of Psychiatry & Neuroscience : JPN
1180-4882
1488-2434
CMA Impact Inc.

39209458
10.1503/jpn.240048
49-4-E263
Psychopharmacology for the Clinician
Clozapine-induced priapism in a man with schizoaffective disorder
Woo Jennifer MD
Eisa Mohamed MBBS
From the Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan
Jul-Aug 2024
29 8 2024
49 4 E263E264
© 2024 CMA Impact Inc. or its licensors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
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pmcA 46-year-old man with schizoaffective disorder presented with inability to urinate because of priapism lasting for more than 48 hours. He had been taking clozapine 100 mg since age 20 years. He reported no previous adverse drug reactions to clozapine and no previous episodes of priapism. No comorbid medical or psychiatric conditions had been diagnosed. The patient had slightly elevated fasting blood glucose levels; however, he did not meet the criteria for diabetes mellitus. He was not taking any other medications, and reported no substance use. His priapism resolved after stopping clozapine and undergoing urgent urologic surgery, but he had permanent penile ischemic damage.

To control his psychiatric symptoms, the patient was started on haloperidol and later quetiapine, which were both unsuccessful owing to adverse effects and lack of effectiveness, respectively. The patient asked to be restarted on clozapine and, following extensive discussion about the risks and benefits, he has been taking clozapine for about 2 years without recurrence of priapism. His family physician monitored his blood glucose levels closely, and appropriate dietary changes were made.

Despite the efficacy of clozapine for psychotic illnesses and treatment-resistant schizophrenia,1 its unique adverse effects, including priapism, warrant caution. Priapism is a prolonged (> 4 hours) penile erection, independent from stimulation or sexual desire. Left untreated, it can result in impotence, urinary retention, and gangrene.2,3 Antipsychotic drugs are thought to cause priapism through their α-1-adrenergic blocking effect in the corpora cavernosa of the penis.4 Priapism is an idiosyncratic reaction, and can appear after initiation, chronic use (as in our patient’s case), dose change, or addition of another medication.5 Reported baseline risk factors for priapism include a history of prolonged and painless erections;6 sickle cell anemia;5 substance misuse;7 diabetes and elevated blood glucose levels;8 polypharmacy, particularly when combining other medications with α-antagonistic activity;9 medications that affect another drug’s metabolism, particularly selective serotonin reuptake inhibitors, highly active antiretroviral therapy, and lithium;6 and a genetic history.10 Although these risk factors may help to stratify patients, it is still largely unknown who will experience (recurrent) priapism. In our patient’s case, both clozapine and his elevated blood glucose levels may have contributed to the development of priapism.

Depending on the clinical scenario, and after ruling out any contributing underlying medical condition, medication or substance use, clinicians may discontinue all antipsychotics completely, switch to an alternate antipsychotic with a lower affinity for α-1-adrenergic receptors, reintroduce clozapine, and/or add a hormonal agent as a protective novel treatment. A recent review reported that, among antipsychotics, risperidone, olanzapine, quetiapine, and clozapine were most associated with the development of priapism,10 correlating with their affinities for α-1-adrenergic blockade.3 Agents that do not have any reported α-1-adrenergic blockade, such as amisulpride and sulpride, have been used successfully in patients who developed priapism with other agents.11 Similar to our patient’s case, there are reports of successful reintroduction of clozapine following resolution of priapism.12–14 Often, these individuals had limited success with other treatments and a high symptom burden. In a recent systematic review,10 only 20% of patients were reported to have recurrent priapism after reinitiating their antipsychotic. It is unclear why the risk of recurrence is low despite the reinitiation of the proposed causative agent.

Finally, goserelin acetate, which acts antagonistically on testosterone plasma levels, has been successfully used in combination with an antipsychotic to keep both psychotic symptoms and priapism in remission. A case report described an individual who had recurrent priapism before the addition of goserelin acetate, who was symptom free while on it, and again experienced recurrent priapism when goserelin acetate was discontinued.15 Although promising, adding goserelin acetate remains largely experimental and requires further research.

Our patient’s case highlights the importance of educating patients on adverse drug reactions, including adverse sexual effects and priapism. Adverse sexual effects are underreported because of their sensitive nature16 and can decrease adherence and cause delays in seeking urgent medical attention when required. Clinicians must take a careful history when initiating clozapine, focusing on medical conditions that could put an individual at increased risk, comorbid medications, substance use, and previous episodes of priapism. In patients who develop a medical condition such as sickle cell disease, diabetes or elevated blood glucose, or who start taking additional medications that have vasoactive properties or α-blocking properties, closer monitoring is warranted. Early detection is paramount, and patients must know that any episodes of priapism should prompt immediate presentation to an urgent care centre to receive the appropriate urologic support.17 Once priapism has occurred, it is important each patient undergoes a thorough review of their medical history to rule out contributing causes, and the appropriate agent to best control their psychiatric symptoms while minimizing their individual risk of recurrence must be chosen collaboratively.

The information in this column is not intended as a definitive treatment strategy but as a suggested approach for clinicians treating patients with similar histories. Individual cases may vary and should be evaluated carefully before treatment is provided. The patient described in this column is a composite with characteristics of several real patients.

Competing interests: None declared.
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