Doug is a 55 yo man with sciatica and recurrent major depression who is taking duloxetine 60mg daily for his pain and mood and has delayed orgasm from the duloxetine. Doug tried to taper duloxetine on two separate occasions in the last 5 years. Each time he stopped the duloxetine the delayed orgasm resolved, and Doug’s depression returned. Doug is currently taking duloxetine 60mg daily. He is euthymic with delayed orgasm that is contributing to relationship strife. He has no problems with libido or erections.
How do you manage SSRI/SNRI-induced sexual side effects?
In Doug’s case, the connection between delayed orgasm and duloxetine is clear from the temporal relationship. However, in general, consider other causes of sexual dysfunction in middle aged men, including cardiac disease, diabetes, alcohol use, hypogonadism (which can cause both sexual dysfunction and major depression), stress (including relationship problems), and medications like beta blockers, antipsychotic medications, and mood stabilizers.
In a previous PsychSnap, we discussed how to ask patients about SSRI/SNRI-induced sexual dysfunction and how to manage it with dose reduction, including drug holidays. In this PsychSnap, we discuss managing SSRI/SNRI-induced sexual dysfunction by switching to another medication, or by treating the sexual side effects with another medication.
| Strategy | Risks | Choose when |
| Switch | Lose the therapeutic benefit of the current medication. The new medication may not be as effective. The new medication may also cause side effects. | First (or maybe second) medication tried. Reasonable expectation that if a relapse occurs, it could be treated successfully as an outpatient. |
| Treat the side effect | Polypharmacy Side effect may not fully resolve. | It took several medication trials to find something effective. Illness severity makes the risks of relapse from switching medications too high. |
Which medication should you switch to?
If there is a compelling reason to continue to use an SSRI/SNRI as treatment, switching to another SSRI/SNRI is reasonable. Just as some people respond to one SSRI but not another one, some people have sexual side effects on one SSRI but not another one. The data is limited, but among the SSRIs, paroxetine and citalopram seem most likely to cause sexual side effects. Fluvoxamine is the SSRI least likely to cause sexual side effects. In the SNRI class, duloxetine is less likely to cause sexual side effects than venlafaxine.
There are also a non-SSRI/SNRI antidepressants that are less likely to cause sexual side effects, specifically bupropion, mirtazapine, vilazodone, and vortioxetine.
Vilazodone (Viibryd) is a “serotonin modulator,” that combines the mechanisms of action of an SSRI and buspirone. Vilazodone was FDA-approved for the treatment of major depressive disorder in 2011 and has also been shown to be effective for GAD in randomized trials (Gommoll, 2015). It is not more effective than SSRIs in treating MDD or GAD, but it may have a lower risk of sexual side effects. I might consider vilazodone in a patient with both MDD and GAD who has had benefit AND sexual side effects from multiple SSRIs.
Vortioxetine (Trintellix) is also a “serotonin modulator” that affects serotonin reuptake (like SSRI/SNRIs) and has agonist, partial agonist, and antagonist effects at multiple other serotonin receptors (the clinical impact of this is unclear). Vortioxetine causes sexual dysfunction less often than the SSRIs. In a large network meta-analysis of antidepressants in major depression, vortioxetine and escitalopram were the two “most effective” and “most acceptable” medications (Cipriani 2018).
Medications with a lower risk of causing sexual side effects than SSRI/SNRIs
| Medication | Advantages | Disadvantages |
| Bupropion (Wellbutrin) | – Treats MDD – Does not cause weight gain – May improve sexual side effects when added to an SSRI/SNRI | – Does not treat GAD, PTSD or OCD |
| Vortioxetine (Trintellix) | – Treats MDD | – Expensive and not available generically – Does not treat GAD – Side effect profile is similar to SSRIs (but with a lower risk of sexual side effects) |
| Mirtazapine (Remeron) | – Treats MDD and (off-label) GAD | – High risk of weight gain and sedation |
| Vilazodone (Viibryd) | – Treats MDD and GAD – Available generically | – Need to take with food for absorption – No advantage in efficacy over SSRI/SNRIs, and some data suggest vilazodone may be less efficacious – Side effect profile is similar to SSRIs (but with a lower risk of sexual side effects) |
| Buspirone (Buspar) | – Treats GAD | – Does not treat major MDD – Smaller effect size than SSRIs for GAD |
| Pregabalin (Lyrica) | – Treats GAD & neuropathic pain | – Does not treat MDD – Controlled substance |
A patient with GAD who has sexual side effects from an SSRI could benefit from switching to either buspirone or pregabalin. A patient with MDD and GAD who has sexual side effects from 2 different SSRIs could switch to vilazodone or mirtazapine as monotherapy, or to the combination of bupropion for MDD AND psychotherapy, buspirone, or pregabalin for GAD.
What medications can be added to SSRI/SNRIs to treat sexual side effects?
There are a handful of medications and herbal supplements that are sometimes added to treat SSRI/SNRI-induced sexual dysfunction. I’m going to cover the two medications that have at least 1 double-blind randomized control trial of moderate size with a clinically significant effect size: bupropion and sildenafil.
Bupropion SR 150mg BID (but not 150mg daily) can improve sexual problems caused by SSRIs. The strongest effect of bupropion was on libido and arousal, but there were improvements in orgasms as well. Women responded better than men. The benefit of bupropion for sexual side effects was seen at 2 weeks and continued to grow over 12 weeks (Safarinejad, 2011). I use bupropion XL 300mg as an equivalent of bupropion SR 150mg BID.
Men with erectile or orgasmic dysfunction from SSRIs improve with the phosphodiesterase inhibitors sildenafil and tadalafil. Surprisingly, sildenafil also improves SSRI-induced orgasmic dysfunction in women! A 2008 double-blind, randomized control trial published in JAMA showed that women had significant improvements in sexual dysfunction from SSRIs with sildenafil (vs placebo) with an effect size of 0.7 (as measured by the Clinical Global Impression for sexual function). Most of this effect was driven by improvements in delayed orgasm and overall sexual enjoyment (Nurnberg 2008).
This study has not been replicated, and a 2013 Cochrane review concluded that for women, it remained uncertain whether sildenafil is more effective than placebo in treating sexual side effects caused by SSRIs (Taylor 2013). However, given the rigor of the JAMA study and the lack of other options for the treatment of delayed orgasm in women, I keep sildenafil in my toolbox for both men and women.
Medications that treat sexual side effects caused by SSRI/SNRIs
| Medication | Efficacy for | Notes |
| Bupropion XL 300mg daily | Libido, arousal > orgasm | Trial should be 2-3 months as efficacy increases over time More effective in women |
| Sildenafil 50-100mg, used 1-2 hours before sex Tadalafil 10mg, used 30 min – 36 hours before sex (dose range 5-20mg) | Delayed orgasm -in women – sildenafil -in men – sildenafil or tadalafil Erectile dysfunction | Consider prescribing sildenafil as Revatio in women.* |
*Because insurance doesn’t cover sildenafil for women, consider prescribing Revatio (a cheaper version of sildenafil) 40mg 1 hour prior to sexual activity. The dose can be increased up to 100mg. With a GoodRx coupon, Revatio costs around $20 out of pocket for sixty 20mg pills.
There are other medications used to treat sexual side effects from SSRI/SNRIs that have an even more limited research base. Small open label trials support the use of mirtazapine 30mg and trazodone 100mg as antidotes for sexual dysfunction, and one RCT trends positively but does not reach significance for buspirone 10-30mg BID. From a nutraceutical perspective, maca 3g daily and saffron 30mg daily have also been studied with some suggestion of benefit (Winter, 2022).
Back to Doug – Doug starts sildenafil as needed 1 hour before sex. At your follow-up visit, Doug tells you that the sildenafil has improved the delayed orgasm significantly, and his partner is very grateful. He continues to take duloxetine 60mg daily.
Key Points
- Drug-induced sexual dysfunction is a common reason that people stop SSRI/SNRIs. By evaluating and managing sexual side effects, we can improve antidepressant treatment adherence.
- If dose reduction or drug holidays aren’t helpful, and this was the first (or second) antidepressant tried, consider switching to another medication that is less likely to cause sexual side effects.
- If it was hard to find an antidepressant that was effective or switching medications seems too risky, try bupropion (particularly for problems with libido or arousal in women) or sildenafil (for delayed or absent orgasm in men or women, or ED in men).
Related PsychSnaps:
“How do you manage the side effects of SSRIs?” Zoe Kopp, January 2024.
“How do you manage SSRI/SNRI induced sexual side effects?” Emma Samelson-Jones, October 2024.
References:
Chauhan, Mohit, Rebecca Parry, and William V. Bobo. “Vilazodone for major depression in adults: pharmacological profile and an updated review for clinical practice.” Neuropsychiatric Disease and Treatment 18 (2022): 1175.
Cipriani, Andrea, et al. “Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.” The Lancet 391.10128 (2018): 1357-1366.
Gommoll, Carl, et al. “Vilazodone in patients with generalized anxiety disorder: a double-blind, randomized, placebo-controlled, flexible-dose study.” International clinical psychopharmacology 30.6 (2015): 297-306.
Jacobsen, Paula L., et al. “Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis.” CNS spectrums 21.5 (2016): 367-378.
Luft, Marissa J., et al. “Pharmacologic interventions for antidepressant-induced sexual dysfunction: A systematic review and network meta-analysis of trials using the Arizona sexual experience scale.” CNS spectrums 27.4 (2022): 496-505.
Nurnberg, H. George, et al. “Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial.” Jama 300.4 (2008): 395-404.
Ozmenler, Nahit Kamil, et al. “Mirtazapine augmentation in depressed patients with sexual dysfunction due to selective serotonin reuptake inhibitors.” Human Psychopharmacology: Clinical and Experimental 23.4 (2008): 321-326.
Safarinejad MR. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. J Psychopharmacol. 2011 Mar;25(3):370-8.
Taylor, Matthew J., et al. “Strategies for managing sexual dysfunction induced by antidepressant medication.” Cochrane Database of Systematic Reviews 5 (2013).
Winter, Joan, et al. “Sexual dysfunction with major depressive disorder and antidepressant treatments: impact, assessment, and management.” Expert Opinion on Drug Safety 21.7 (2022): 913-930.
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