Post-SSRI Sexual Dysfunction

AF is a 32-year-old female that recently presented into the clinic with what she described as female sexual dysfunction. She had been on 75mg Wellbutrin and 225mg Effexor for 10 years, which she tapered off and stopped 8 months ago as her anxiety has been much better. However, since having been with a new partner she noticed that she wasn’t able to reach orgasm as she had in the past and now the area felt numb if she kept stimulating it, as if her senses were not connecting. Even when trying to please herself on her own, she couldn’t reach climax, whereas she was able to in the past. She said she feels a bit of arousal then it stops, nothing happens afterwards. She had seen her gynecologist, where all physical examinations and tests were normal as well as has a referral to see a psychologist in the near future for the condition. But it led me to wonder if the effects of being on the antidepressant medications could truly have an impact on her sexual function even while having stopped the medications for several months afterwards? 

Wellbutrin’s (or Bupropion) mode of action is not well understood but it is proposed to be a norepinephrine dopamine reuptake inhibitor, acting through dopaminergic or noradrenergic pathways (1). Effexor (or Venlafaxine) is a selective serotonin and norepinephrine reuptake inhibitors and weak dopamine reuptake inhibitor (2). Both of the medications have listed cautions of “may cause sexual dysfunction” (1, 2), and it is generally accepted that antidepressants may cause antidepressant-induced sexual dysfunction (3). However, it appears that the antidepressant class of selective serotonin reuptake inhibitors (SSRIs) have the biggest impact on causing sexual dysfunction, wherein between 30-60% of SSRI medicated patients may present with some form of sexual dysfunction (3). 

And after having looked into the topic further, it appears that there is an emerging branch of studies recognizing post-SSRI sexual dysfunction (PSSD) (3, 4). David Healy, MD reports that there have been cases of PSSD since 1991, though it wasn’t until 2006 that a formal PSSD syndrome was reported (4). 

PSSD can occur in all ages, sexes and ethnic groups (4). It may happen after only a few doses of treatment and may affect an individual long after having stopped the medication. Symptoms are genital numbing, decreased or loss of orgasm and libido that can persist or even be exacerbated after stopping the SSRI. It’s proposed that serotonin reuptake inhibitors may cause sensory changes similar to lidocaine through late sodium currents, resulting in the numbing sensation that may be more noticed in the genital area due to its functional consequences (4). Other theories are that long-term use of SSRIs may cause a downregulation or desensitization of 5-hydroxytryptamine receptor 1A (5HT1A), which is involved in regulating sexual motivation (5). Another suggests that there may be an individual vulnerability to serotonin as not everyone on SSRIs go on to develop PSSD (5). 

Diagnosis can be difficult as sexual desire and function can also be affected by mental illness and there is a question of whether it is from stopping the medication or if it is PSSD; therefore, a thorough case history is important. Other factors to consider are also age, smoking, alcohol, and substance abuse as they may affect sexual dysfunction symptoms; and other diseases such as diabetes, hypertension and depression (5). 

There is no definitive treatment for PSSD, and some cases may spontaneously resolve. Cognitive-behavioral therapy, as well as buspirone, trazodone, donepezil, ketamine, metformin, and mirtazapine have been tested as PSSD treatments, with varying degrees of success (5). 

Whether AF’s case is a form of PSSD is yet to be determined. Nevertheless, it was interesting to see that there is a branch of PSSD being acknowledged. It stresses even more so the importance of thorough case taking regarding sexual function prior, during, and after prescribing antidepressants as well as informing patients about the potential of PSSD prior to prescribing SSRIs.  


  1. Medscape –
  2. Medscape –
  3. Gregorian RS, et al. Ann Pharmacother. 2002 Oct;36(10):1577-89. doi: 10.1345/aph.1A195.
  4. Healy, D. Epidemiology and Psychiatric Sciences. 2019.
  5. Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A Literature Review. Sex Med Rev 2018;6:29e34.