Antidepressants with fewer sexual side effects?

Search for the antidepressant with the fewest sexual side effects and you will find lists naming bupropion, mirtazapine and agomelatine, because some studies counted fewer sexual problems with them during treatment than with SSRIs such as sertraline and citalopram. But none of those studies followed anyone after they stopped, and no list can tell you which medicine is right for you.

So the lists answer a smaller question than the one they seem to. They cannot tell you which medicine is safe for your sex life, and we will not pretend they can. As a charity we never recommend a medicine, or one medicine over another. What we can show you is how these figures are made, and what they leave out.

Where the “fewer side effects” lists come from

Most of them trace back to a handful of studies, and it is fair to say what they found.

A 2009 meta-analysis, which pooled studies that asked people about sex directly, found ten antidepressants linked to significantly more sexual dysfunction than a placebo (a dummy pill). They included sertraline, citalopram, paroxetine and venlafaxine, with rates from 25.8% to 80.3%. Bupropion, mirtazapine, agomelatine and moclobemide showed no significant difference from placebo. A US survey of 6,297 people found sexual dysfunction in 22% of those on one form of bupropion, against 36% to 43% for SSRIs, mirtazapine and venlafaxine.

That is the evidence behind the lists. Two facts about that evidence are rarely mentioned with the lists. A 2014 review of 63 studies rated the overall strength of its evidence as low, and noted that sexual problems are common in depression itself. And in the UK, bupropion is not licensed as an antidepressant at all: its UK licence, as Zyban, is to help people stop smoking.

In the UK, an SSRI is usually the first antidepressant offered. Antidepressants help many people, and some rely on them. Nothing on this page is a reason to stop one.

The same drug, a different number

A side effect rate is not a fixed property of a medicine. It depends on who was studied, for how long, and above all whether anyone asked.

The clearest example is in the US prescribing information for vortioxetine, one of the newer antidepressants. In its 6 to 8 week trials, 5% of men on the top dose raised a sexual side effect themselves. When the same kind of trials used a questionnaire about sex, 29% of men whose sexual function had been normal developed a problem.

Vortioxetine 20 mg in men: how asking changes the answer

Raised it themselves: placebo2%

Raised it themselves: vortioxetine5%

Questionnaire: placebo14%

Questionnaire: vortioxetine29%

The same effect runs through the older studies. When a Spanish study of 1,022 outpatients asked everyone directly, 58% to 73% of those on an SSRI or venlafaxine developed a sexual problem. In the US survey, doctors consistently underestimated how common sexual dysfunction was.

The low figures are also the least certain. In the Spanish study, mirtazapine’s rate of 24.4% came from 49 people, and moclobemide’s 3.9% was one person out of 26. The studies do not even agree with each other: the US survey put mirtazapine in the same band as the SSRIs. They used different questionnaires, which the 2009 meta-analysis names as a limit on its own comparison, and the Spanish data were collected between 1995 and 2000.

For agomelatine, the UK product information reports a pooled analysis of trials that found no link with sexual dysfunction, during the time people were taking it. And lower is not none. In a 2024 study of the WHO’s global database of side effect reports, agomelatine, bupropion and mirtazapine had a weaker link to sexual problems than most SSRIs and SNRIs, but the link was still there. A reporting database cannot say how often anything happens.

What none of the rankings measured

The question that matters to anyone with PSSD is what happens after the last tablet. None of the studies behind the lists was designed to answer it.

For SSRIs and SNRIs, regulators have answered part of it. In 2019 the European Medicines Agency added a warning to every one of them about long-lasting sexual dysfunction that continued after stopping. The same review looked at vortioxetine, and the warning was not added to it. That was a judgement on the evidence in 2019, not a finding that it cannot happen. Our page on which antidepressants carry the PSSD warning has the full list.

For the drugs at the top of the lists, far less is known, and less known is not the same as safe.

• Mirtazapine. The 2022 diagnostic criteria mention reports of lasting symptoms that resemble PSSD, and say there is not enough data to know if it is the same condition.
• Trazodone. One published case of persistent genital arousal disorder, in a woman who had taken it in the past. One case shows that something can happen, never how often.
• Bupropion and agomelatine. We found no published case reports.

Finding no reports is different from finding no risk. Sexual side effects are under-reported, partly because patients and doctors may be reluctant to discuss them, as the vortioxetine label itself notes. Even for SSRIs, the most studied group, a 2023 systematic review could not find a reliable estimate of how often the problems last. Published figures range very widely. For every other drug named on this page, we found no figures at all.

The SIDEfxHUB registry cannot supply that number, because its members chose to join. What it can do is follow people with lasting symptoms over time, whichever antidepressant they took, and show researchers what the trials never looked at.

What to ask before you start, or if you are already taking one

Asking about sex before starting an antidepressant is a normal question, and it is expected. In England, NICE guidance on depression says the harms discussed before prescribing should include side effects you want to avoid, and gives sexual function as an example. For long-term use, it lists long-term effects on sexual function as a risk to discuss.

Your prescriber may not have come across lasting sexual side effects, although the UK product information for SSRIs such as sertraline mentions them. These questions help to get past a single percentage:

• How common are sexual side effects with this medicine, and where does that figure come from?
• Were people asked directly, or only counted if they raised it themselves?
• Does the leaflet mention sexual problems that continue after stopping?
• If something changes, how will we tell the medicine apart from the depression?
• If I want to stop one day, how would we plan that together?

Why does this so rarely come up in an appointment? A psychiatrist explains in this nine-minute video from Taper Clinic, a private service that is not connected to us. We link the explanation, not the business.

If the side effects did not stop

You can report it yourself, whichever antidepressant you took. Regulators file reports under a code, and one exists for this.

A lower number on a list is not a promise, and a missing number is not a reassurance. The honest answer to “which antidepressant has the fewest sexual side effects” is that nobody has reliably measured the part that lasts. A report records one reaction at one moment. The registry records a person over time, which is the kind of record research on lasting side effects needs.

If you are struggling with your mental health, the Samaritans are on 116 123 in the UK, free, at any hour. In the US, call or text 988.