Nora is a 26 yo woman who reached out to you, her PCP, during her first episode of severe major depression (PHQ9 20). You prescribed sertraline and connected her with psychotherapy. After taking sertraline 100mg daily for a month, Nora’s depressive symptoms went into remission (PHQ9 3). At your next follow up visit, you ask if Nora is having any side effects from the sertraline.
“I don’t think so,” she says, with a slight hesitation.
“That sounds like you are unsure,” you say.
Nora blushes slightly. “Now that my depression is better, I have my energy back. My sex drive is back too, but it’s so much harder to…” she trails off.
“Climax?” you say.
“Yes.”
How do you manage SSRI/SNRI-induced sexual side effects?
Sexual side effects include problems with libido, arousal, and orgasm. Low libido is a medication side effect and is also a common symptom of depression. Problems with arousal or orgasm are more commonly medication side effects.
Patients are unlikely to spontaneously report sexual side effects from antidepressants. One study of 344 people taking SSRIs found that 58% of patients reported sexual dysfunction if physicians asked about it directly, while only 14% spontaneously reported sexual side effects (Monetejo 1997). Sexual side effects can be problematic for patients and their relationships; they are also a common reason for antidepressant non-adherence.
Any antidepressant that causes significant serotonin reuptake inhibition, including both SSRIs and SNRIs, has a high risk of causing sexual side effects. 50-80% of people taking SSRIs have sexual side effects. 40-70% of people taking antipsychotic medications also experience sexual side effects, albeit through different mechanisms.
Asking about Sexual Side Effects
Screening: [Medication name] can affect sexual functioning and sometimes cause problems with libido, arousal, or ability to orgasm. Have you noticed any problems with your sexual functioning?
What has changed?
- Have you noticed any changes in your sex drive or libido?
- Have you noticed any changes in your arousal (erections/lubrication)?
- Have you noticed problems with having an orgasm?
- Is the orgasm less pleasurable?
Timing: When did [the symptom] start?
- Before depression?
- During depression but before medication?
- After medication (at the starting dose or after a certain dose)?
Context:
- Do you experience [the symptom] by yourself (masturbation)?
- Do you experience it with a partner?
Impact: How much are you bothered by [the symptom]?*
*The severity of sexual side effects is only loosely correlated with how much someone is bothered by them. I’ve met patients who are willing to tolerate a complete block to their sexual functioning given the mood benefits of an antidepressant and other patients who find even mild changes in sexual functioning intolerable.
Back to Nora – You learn from Nora that her baseline sexual functioning was good, and she regularly had orgasms both by herself and with her partner. She lost her libido when she was depressed. When she was taking sertraline 50mg daily, she was still depressed with a low sex drive, but she didn’t have problems with arousal or orgasm. After taking sertraline 100mg for a month, Nora’s depression resolved and her sex drive returned. However, she no longer had orgasms with her partner, which was a big loss. She could still achieve orgasm with masturbation but it took a lot more time and stimulation. She did not have problems with arousal.
Managing SSRI/SNRI-induced sexual side effects
Note – the broader differential diagnosis of sexual dysfunction is not covered here.
The sexual side effects of antidepressants are often dose dependent. Deprescribing, dose reduction, or drug holidays are my first steps to consider in managing SSRI/SNRI sexual side effects if a patient is doing well psychiatrically on the current medications. We are fine tuning the dose, trying to discover a sweet spot where psychiatric symptoms are controlled and sexual side effects are tolerable.
Patients risk experiencing a relapse of their symptoms with dose reduction, so they should be monitored closely. These strategies are higher risk in patients who have required multiple medication trials to achieve stability, or patients with a history of very severe illness.
| Strategy | Details | Caveats and Next Steps |
| Deprescribe | If there is not an indication for continuing the SSRI/SNRI | See prior PsychSnap on how to stop SSRIs. |
| Reduce the dose | Particularly if a patient is on a moderate or high dose SSRI/SNRI | If sexual side effects improve with dose reduction, but psychiatric symptoms return, consider maintaining the lower dose of the SSRI and adding in an augmentation agent. For major depression – aripiprazole, mirtazapine or lithium For GAD – buspirone or pregabalin |
| Drug holidays | Intentionally skipping 1-2 doses of an antidepressant before sex such that blood levels drop sufficiently to allow for temporarily improved sexual functioning. | Scheduled sex must be acceptable to the patient. Drug holidays will not work with medications with long half-lives like fluoxetine, but can work for any of the other SSRI/SNRIs. |
How do drug holidays work?
The patient skips 1-2 doses of an antidepressant prior to planned sex. Because the efficacy for SSRIs and SNRIs for depression and anxiety is due to downstream effects (that’s why they take 2-3 weeks to start to work!), a temporarily lowered blood level does not necessarily affect the clinical efficacy of the medication. However, the effect of SSRIs on sexual functioning is commonly dose dependent, so temporarily lowered blood levels can improve sexual functioning. A small study showed that patients dropping their blood level by 50-73% had some improvement in sexual functioning (Rothmore 2020).
Some people develop SSRI/SNRI withdrawal symptoms with drug holidays, particularly if they are taking a medication with a shorter half-life (venlafaxine, duloxetine, paroxetine). For many patients, however, drug holidays offer a window of opportunity when they can achieve enjoyable sex without withdrawal symptoms and without destabilizing their mood or anxiety disorder.
Other Strategies
If there isn’t a sweet spot where psychiatric symptoms are controlled and sexual side effects are tolerable, consider either switching the SSRI/SNRI to another medication, or treating the sexual side effects with another medication.
| Strategy | Details | Caveats and Next Steps |
| Switch the SSRI/SNRI to another medication | Medications that are less likely to cause sexual side effects: for depression bupropion, mirtazapine, vilazodone, vortioxetine for anxiety buspirone, pregabalin, vilazodone, mirtazapine | This may be higher risk in patients who have required multiple medication trials to achieve stability or in patients with a history of very severe illness. |
| Treat the sexual side effects (and continue the effective dose of an SSRI/SNRI) | Details to follow in a future PsychSnap | There are several strategies that may help, but the data is limited |
What about watchful waiting? Watchful waiting can be considered if the clinical benefit of a medication is substantial and the sexual dysfunction is mild. However, only 10% of patients get substantial improvement in sexual side effects from SSRI/SNRIs over 4-6 months without a medication change (Clayton 2006).
Back to Nora
Nora’s major depression remitted with sertraline 100mg, but she also developed delayed orgasm at this dose. She did not benefit from or have sexual side effects from sertraline 50mg. You first look for the sweet spot – a dose that would work for depression without causing bothersome sexual side effects. Nora decreased the sertraline to 75mg daily. Her sexual side effects were moderately better within a few days on the lower dose, but her depressive symptoms started to return after a month.
You discussed the options of returning to sertraline 100mg daily and trying drug holidays or trying another medication to treat the delayed orgasm, or switching to another medication. Nora didn’t want to add another medication and was nervous about switching medications, but she was open to trying drug holidays.
Nora increased her sertraline dose back to 100mg daily, and fortunately, her depression remitted again. After a month of remission, she tried a drug holiday with the goal of sex on Saturday night. Sertraline has a half life of ~26 hours. In planning for sex on Saturday night, Nora skipped the sertraline on Friday and Saturday mornings, dropping her sertraline blood level to less than 25% of her baseline after more than 2.5 sertraline half-lives by Saturday night. At that point, her sexual functioning was back to baseline, and she was able to orgasm with her partner. After sex, she took sertraline 100mg on Saturday at bedtime and then resumed taking sertraline 100mg daily on Sunday morning. Her mood remained stable.
Look for a future PsychSnap that will offer more details about switching antidepressants to avoid sexual side effects and treating sexual side effects with other medications. Some additional information on medications to treat sexual side effects is available in the table at the end of “How do you manage the side effects of SSRIs“?
Key Points
- Ask your patients taking SSRIs/SNRIs about their sexual functioning on the medication.
- Strategies to manage sexual side effects include deprescribing, reducing the dose, temporarily reducing the dose via drug holidays, switching medications, adding a medication to treat the side effect, and accepting the sexual side effects given the benefits of the medication.
Related PsychSnaps:
“How do you manage the side effects of SSRIs?” Zoe Kopp, January 2024.
Patient instructions for starting SSRIs that includes a heads up to patients about the risk of sexual side effects.
References:
Clayton AH, Montejo AL. Major depressive disorder, antidepressants, and sexual dysfunction. J Clin Psychiatry. 2006;67 Suppl 6:33-7.
Montejo-González AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997; 23: 176–194.
Rothmore J. Antidepressant‐induced sexual dysfunction. Medical Journal of Australia. 2020 Apr 30;212(7).
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