No SSRI is Free of Ejaculatory Side Effects
Unfortunately, there is no SSRI that treats depression and anxiety without causing ejaculatory disorders—all traditional SSRIs cause ejaculatory delay or failure, which is precisely why they are used therapeutically for premature ejaculation. 1, 2
Understanding the Problem
All SSRIs work by the same mechanism—blocking serotonin reuptake—which inherently causes ejaculatory dysfunction in men. The FDA label for sertraline documents ejaculation failure (primarily delayed ejaculation) in 14% of male patients versus 1% on placebo. 3 However, these numbers likely underestimate the true incidence, as patients and physicians are often reluctant to discuss sexual side effects. 3
Ranking SSRIs by Ejaculatory Impact
If you must use an SSRI, here is the evidence-based ranking from least to most ejaculatory dysfunction:
Lowest Risk (but still present):
- Fluvoxamine causes the least ejaculatory delay among SSRIs—a controlled trial showed it increased ejaculation time to only ~40 seconds versus ~110 seconds for other SSRIs, and did not differ significantly from placebo (p=0.38). 4 The AUA guideline even suggests fluvoxamine may be "ineffective for treatment of premature ejaculation," implying minimal ejaculatory delay. 2
Moderate Risk:
Sertraline (50-200 mg daily) causes significant ejaculatory delay with 14% experiencing ejaculation failure versus 1% on placebo. 3 It is effective for premature ejaculation treatment, confirming substantial sexual side effects. 2
Fluoxetine (20-40 mg daily) causes similar ejaculatory delay to sertraline, with controlled trials showing ~110 seconds ejaculation time. 4 One study found fluoxetine was associated with impaired sexual function in patients with depression/anxiety. 5
Highest Risk:
Paroxetine (10-40 mg daily) causes the strongest ejaculatory delay of all SSRIs—increasing ejaculation time 8.8-fold over baseline and up to 420-480% in controlled trials. 1, 6, 4 The American College of Physicians confirms paroxetine has the highest rates of sexual dysfunction among all SSRIs. 2
Escitalopram also causes significant ejaculatory dysfunction (OR 3.04 for erectile dysfunction versus placebo). 7
Better Alternatives for Depression/Anxiety Without Ejaculatory Dysfunction
If avoiding ejaculatory side effects is the priority, you should not prescribe an SSRI at all. Consider these alternatives:
Non-SSRI Antidepressants with Minimal Sexual Side Effects:
Agomelatine showed similar EjD incidence to placebo and had favorable SUCRA rankings for avoiding sexual side effects. 7
Vortioxetine had top-five SUCRA values for avoiding ejaculatory dysfunction, erectile dysfunction, and decreased libido. 7
Vilazodone demonstrated top-five SUCRA rankings across all sexual adverse events and had satisfactory performance for adverse events and withdrawal rates. 7
Trazodone exhibited similar EjD incidence to placebo and had excellent SUCRA values for avoiding sexual side effects. 7
Bupropion is recommended by the American College of Physicians as a standard switching strategy for SSRI-induced sexual dysfunction. 2
Critical Safety Considerations
Never combine SSRIs with MAOIs due to risk of potentially fatal serotonin syndrome (symptoms: tremor, hyperreflexia, agitation, diaphoresis, fever, seizures, rhabdomyolysis). 1, 2
Never abruptly discontinue SSRIs—always taper gradually to prevent withdrawal syndrome (dizziness, nausea, headache, flu-like symptoms). 2, 8
Monitor for suicidal ideation in patients under age 24 and those with comorbid depression, though this risk has not been found specifically in non-depressed men with PE. 1, 2
Avoid SSRIs in bipolar depression due to risk of precipitating mania. 1, 6
Practical Clinical Approach
If the patient is already on an SSRI and experiencing ejaculatory dysfunction, reduce the dose to the minimum effective level for depression control, as sexual side effects are strongly dose-related. 2 If this fails, switch to bupropion, vortioxetine, vilazodone, trazodone, or agomelatine rather than trying different SSRIs. 2, 7