Trazodone, marketed under brand names like Desyrel and Oleptro, is a medication primarily prescribed to manage major depressive disorder. Because of its strong sedative properties, it is frequently used off-label at low doses to treat insomnia. While it is generally considered to have a lower risk of certain sexual problems compared to other antidepressants, the drug is associated with a distinct set of sexual adverse effects.
Trazodone’s Specific Sexual Adverse Effects
The most recognized and serious sexual complication associated with Trazodone is priapism, a prolonged erection that persists without sexual stimulation and often becomes painful. This condition is a medical emergency requiring immediate attention if the erection lasts four hours or longer, as delayed treatment can lead to permanent tissue damage and erectile dysfunction. Priapism is rare, affecting an estimated less than one percent of male patients, or approximately one in 6,000 users, but it can occur at any dosage and even after the first administration.
Changes to sexual desire are also reported, though the effect is variable. While some patients report a decreased libido (affecting about one percent of users), others, including both men and women, report an increase in sexual desire (less than two percent). This demonstrates that Trazodone’s impact on desire can manifest in two opposite ways.
Male patients may also experience difficulties related to orgasm and ejaculation, such as delayed ejaculation or, less commonly, absent ejaculation. The drug’s effects are not limited to men; women have reported rare conditions analogous to priapism, such as clitorism or persistent genital arousal disorder (PGAD). These serious effects involve unwanted, persistent genital engorgement that can be distressing.
How Trazodone Affects Sexual Function
Trazodone is classified as a Serotonin Antagonist and Reuptake Inhibitor (SARI), meaning it blocks certain receptors while inhibiting the reuptake of serotonin. The drug’s unique and most concerning sexual side effect, priapism, is directly linked to its potent antagonism of alpha-1 adrenergic receptors. These receptors are located on the smooth muscle lining the blood vessels and tissue of the penis.
Normally, alpha-1 receptors help regulate blood flow by signaling the smooth muscles to contract, which restricts blood from filling the erectile tissues and maintains a non-erect state. Trazodone blocks this signal, causing the smooth muscles in the corpus cavernosum to relax uncontrollably. This relaxation leads to excessive blood flow into the penis while simultaneously impeding the necessary outflow, resulting in a prolonged, rigid erection.
Trazodone’s action on serotonin receptors also influences sexual function. The medication is a strong antagonist of the 5-HT2A and 5-HT2C serotonin receptors. These receptor types are known to play a role in inhibiting sexual response, including desire and orgasm. By blocking these inhibitory receptors, Trazodone can sometimes mitigate the generalized sexual dysfunction, such as loss of libido, that is commonly caused by other classes of antidepressants like Selective Serotonin Reuptake Inhibitors (SSRIs).
Clinical Strategies for Managing Sexual Side Effects
The most straightforward initial strategy for addressing Trazodone-induced sexual side effects is a dosage adjustment. Since the risk of adverse effects, particularly priapism, is considered dose-dependent, a physician may attempt to lower the daily dose to see if the symptoms subside. If a dose reduction is ineffective or inappropriate for treating the underlying condition, the physician may recommend discontinuing Trazodone entirely and switching to an alternative medication.
For managing milder symptoms like erectile dysfunction (ED) that do not involve priapism, some physicians may consider co-administering a phosphodiesterase-5 (PDE5) inhibitor, such as sildenafil or tadalafil. This strategy aims to improve erectile function while the patient continues taking Trazodone. However, this approach must be carefully managed by a clinician, as Trazodone is not a first-line treatment for ED.
In the case of priapism, immediate medical intervention is mandatory to prevent permanent damage to the erectile tissue. Treatment for ischemic priapism typically involves the aspiration of blood from the corpus cavernosum and the intracavernosal injection of sympathomimetic agents, such as phenylephrine, to induce smooth muscle contraction and allow blood to drain. Patients who experience persistent genital arousal disorder or clitorism should also discontinue the medication, as this adverse effect may resolve after the drug is stopped.