Which antidepressant is most commonly associated with sexual side effects, specifically sexual dysfunction?

From the Guidelines

Paroxetine is the antidepressant with the most sexual side effects, as it has been associated with higher rates of sexual dysfunction compared to other second-generation antidepressants. According to a clinical practice guideline from the American College of Physicians 1, paroxetine had higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline. The study found that bupropion had a significantly lower rate of sexual adverse events than fluoxetine or sertraline, suggesting that it may be a better option for patients concerned about sexual side effects.

Some key points to consider when evaluating the risk of sexual side effects with antidepressants include:

• The mechanism behind these effects, which relates to increased serotonin levels inhibiting dopamine and norepinephrine pathways involved in sexual response
• The incidence of sexual dysfunction, which can occur in approximately 50-80% of patients taking SSRIs, with paroxetine showing rates at the higher end of this range
• Alternative treatments with lower rates of sexual dysfunction, such as bupropion, mirtazapine, and vilazodone
• Strategies to minimize sexual side effects, including adding bupropion to an SSRI regimen or taking medication after sexual activity when possible.

It's essential to weigh the benefits and risks of each medication and consider individual patient factors when selecting an antidepressant, as the risk of sexual side effects can vary depending on the specific medication and patient population 1.

From the FDA Drug Label

Male and Female Sexual Dysfunction With SSRIs Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Table 6 Incidence of Sexual Adverse Events in Controlled Clinical Trials PAXIL Placebo n (males) 1446 1042 Decreased Libido 6-15% 0-5% Ejaculatory Disturbance 13-28% 0-2% Impotence 2-9% 0-3% n (females) 1822 1340 Decreased Libido 0-9% 0-2% Orgasmic Disturbance 2-9% 0-1%

The antidepressant with the most sexual side effects is paroxetine (PAXIL), with reported incidence rates of:

• Decreased Libido: 6-15% in males and 0-9% in females
• Ejaculatory Disturbance: 13-28% in males
• Impotence: 2-9% in males
• Orgasmic Disturbance: 2-9% in females 2

From the Research

Antidepressants with the Most Sexual Side Effects

• Selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) are associated with a higher risk of sexual dysfunction, including erectile dysfunction, decreased libido, and orgasmic dysfunction 3, 4, 5
• Specific SSRIs, such as sertraline and paroxetine, have been reported to cause sexual dysfunction in approximately 30-70% of patients 4
• Tricyclic antidepressants, except clomipramine, and mirtazapine are associated with a lower risk of sexual dysfunction compared to SSRIs and SNRIs 3
• Bupropion, moclobemide, agomelatine, reboxetine, and vilazodone are associated with a lower risk of sexual dysfunction and may be considered as alternative treatment options 3, 6, 5

Comparison of Antidepressants

• A study comparing the risk of sexual dysfunction with individual antidepressants found that SSRIs and SNRIs had the highest risk, while bupropion and nefazodone had a lower risk 7
• Another study found that switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction compared to restarting sertraline 6
• A review of articles on sexual dysfunction and depression found that different classes of antidepressants vary in their ability to cause sexual side effects, with SSRIs and SNRIs being the most likely to cause sexual dysfunction 5

Management of Antidepressant-Induced Sexual Dysfunction

• Management strategies for antidepressant-induced sexual dysfunction include switching to a different antidepressant, adding a medication to treat the sexual dysfunction, and behavioral or psychological interventions 3, 6
• Phosphodiesterase inhibitors, such as sildenafil and tadalafil, have been found to be effective in treating erectile dysfunction in men with antidepressant-induced sexual dysfunction 6
• Bupropion has been found to be effective in treating sexual dysfunction in women with antidepressant-induced sexual dysfunction 6