What is the cause of priapism associated with trazodone (antidepressant medication)?

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From the Guidelines

Trazodone can cause priapism through its alpha-adrenergic blocking effects, particularly at the alpha-1 receptors in penile tissue, leading to a prolonged, painful erection that persists without sexual stimulation. This medication, commonly used for depression, insomnia, and anxiety, interferes with normal detumescence mechanisms by causing smooth muscle relaxation in the corpus cavernosum, leading to increased blood flow into the penis while simultaneously reducing outflow 1. The risk of priapism appears to be dose-dependent, though it can occur at any dosage and even after a single dose. Men with sickle cell disease, leukemia, or other conditions predisposing them to priapism should use trazodone with particular caution.

Key Points to Consider

  • Priapism is a rare but serious side effect of trazodone, occurring in approximately 1 in 6,000 male patients, and is considered a medical emergency requiring immediate attention if an erection lasts longer than 4 hours 1.
  • The goal of the management of a patient with priapism is prevention of future episodes while management of each episode should follow the specific treatment recommendations for ischemic priapism 1.
  • If priapism develops, immediate medical attention is necessary as untreated cases can lead to permanent erectile dysfunction due to penile tissue damage 1.

Management and Prevention

  • Management strategies for patients with stuttering priapism have historically included prevention of priapism episodes with systemic therapies, early intervention by the patient with self-injection of sympathomimetic agents, and, as a last resort, surgical placement of a penile prosthesis 1.
  • Systemic therapies proposed for the prevention of priapism have included hormonal agents, baclofen, digoxin and terbutaline, although terbutaline has been shown to be effective in the management of prolonged erections, there is little evidence to support its use in this clinical setting 1.

From the FDA Drug Label

Cases of priapism (painful erections greater than 6 hours in duration) have been reported in men receiving Trazodone Hydrochloride Tablets. Trazodone Hydrochloride Tablets should be used with caution in men who have conditions that might predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia), or in men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie’s disease).

The cause of priapism from trazodone is not explicitly stated in the label, but it can occur in men receiving trazodone, particularly those with certain conditions that may predispose them to priapism 2.

From the Research

Cause of Priapism from Trazodone

The cause of priapism from trazodone is not fully understood, but several studies suggest that it may be related to the drug's alpha-adrenergic blocking effects 3.

  • Mechanism of Action: The exact mechanism of how trazodone causes priapism is still not fully understood, but it is thought to be related to the drug's ability to block alpha-adrenergic receptors, which can lead to an increase in blood flow to the penis and cause an erection 3.
  • Risk Factors: Several studies have identified risk factors for priapism in patients taking trazodone, including:
    • Doses of 150 mg/day or less 4
    • Age, with all age groups appearing to be vulnerable to this adverse effect 4
    • Introduction of trazodone to a patient, resulting in the immediate development of priapism 3
    • Change in drug plasma concentration due to a change in drug dosage or comedication with certain SSRIs 3
  • Incidence and Prevalence: The incidence and prevalence of priapism in patients taking trazodone are not well established, but several case reports and studies have documented the occurrence of priapism in patients taking the drug 5, 6, 4, 3, 7.
  • Screening and Counseling: Patients should be informed of the potential risk of priapism and instructed to discontinue the medication if any unusual erectile problems develop 4. Prescribing physicians should also appropriately screen and educate patients prior to trazodone initiation and instruct patients to report any treatment side effects to avoid potential long-term adverse outcomes 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Priapism induced by various psychotropics: A case series.

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2019

Research

Trazodone and priapism.

The Journal of clinical psychiatry, 1987

Research

Priapism associated with trazodone therapy.

The Journal of urology, 1988

Research

[Refractory ischemic priapism due to trazodone].

Revue medicale de Liege, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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