Selective serotonin reuptake inhibitors, post-treatment sexual dysfunction and persistent genital arousal disorder: A systematic review
Livio Tarchi; Giuseppe Pierpaolo Merola; Ottone Baccaredda-Boy; Francesca Arganini; Emanuele Cassioli; Eleonora Rossi; Mario Maggi; David S. Baldwin; Valdo Ricca; Giovanni Castellini
Pharmacoepidemiology and Drug Safety2023
In plain terms
Researchers searched three medical databases, up to December 2022, for reports of sexual problems that carried on, or began, after people stopped taking an SSRI antidepressant. They found 19: two small treatment studies with no comparison group, six studies such as surveys and collections of reports, and 11 reports on single patients or small groups. Most described problems that began while people were on the drug and did not go away after stopping; unwanted, persistent genital arousal (PGAD) after stopping was described only in women. The researchers concluded the evidence was too weak to say how common these problems are or to show the drug caused them, though lasting problems could not be ruled out.
What it doesn’t show: It can't say how common these problems are, what causes them or what helps: the 19 reports were few, small and mostly without comparison groups, and the review did not combine their numbers.
Summary (paraphrased)
The authors systematically reviewed clinical evidence on sexual dysfunction persisting after SSRI discontinuation and on persistent genital arousal disorder (PGAD) linked to SSRIs. Eligible studies comprised two retrospective interventional studies, six observational studies, and eleven case reports. They found the literature insufficient to produce reliable prevalence estimates or to establish a cause-effect relationship, though continued sexual disturbance after stopping could not be entirely ruled out and persisting dysfunction may be linked to relapse of depression or anxiety; they stated that their findings support the EMA's caution about possible continued sexual disturbance after discontinuation. PGAD was reported in 6 of the 19 studies, and the authors described post-SSRI PGAD only in women and only in case reports. The review cataloged reported symptoms and the treatments that have been attempted, highlighted how thin the evidence base remains, and cautioned against routine early SSRI discontinuation.
Evidence
Extracted from the full text; page numbers refer to the paper. The library’s own notes are labelled as such.
- Design
- Systematic reviewSystematic review following PRISMA 2020, with a protocol registered in advance (PROSPERO CRD42021273886); narrative synthesis, no meta-analysis
- Setting
- PubMed, Embase and Google Scholar; English-language papers only; last search December 2022
- Population
- Published clinical data (observational or experimental studies, case series and case reports) on SSRI use with sexual dysfunction persisting, or first appearing, after treatment stopped, and on PGAD after SSRI discontinuation. Reviews, meta-analyses, opinion articles, animal studies and methods papers were excluded.
- Size
- 19 · 19 studies (2 retrospective interventional, 6 observational, 11 case reports) from 859 records; 73 duplicates removed, 571 excluded on title and abstract, 196 on full text (193 on criteria, 3 not in English)
- Exposure
- SSRIs; included reports also covered SNRIs (venlafaxine, desvenlafaxine, duloxetine) and tricyclics (clomipramine, amitriptyline)
- Compared with
- None (narrative synthesis); both interventional studies were uncontrolled
- Outcome
- Prevalence or incidence, timing of onset relative to SSRI treatment, reported symptoms and attempted treatments, for PSSD and for post-SSRI PGAD. Risk of bias rated with JBI checklists, ROBINS-I and RoB 2.
- Follow-up
- Not applicable (review). Included case reports followed patients for up to 2 years; the longest illness duration reported was 23 years
Key results
- No reliable estimate of the prevalence of PSSD or post-SSRI PGAD could be made, and a cause-effect relationship between SSRI exposure and persistent sexual impairment could not be ascertained; continued disturbance after stopping "could not be entirely ruled out" · pp. 1053, 1056, 1064
- Average risk-of-bias score at least medium or higher; the authors judge most included reports at high risk of bias · pp. 1056, 1064
- In most studies, sexual dysfunction arose during SSRI treatment and did not recede after stopping. Reported symptoms ranged widely (e.g. penile anaesthesia, pleasureless orgasm, loss of libido, emotional blunting, loss of nocturnal erections, reduced semen volume, reduced taste and smell); most overlap with on-treatment side effects or with depression, except nipple and genital anaesthesia · pp. 1056–1057, 1063
- PGAD was reported in 6 of the 19 studies. In the text, post-SSRI PGAD was described only in women and only in case reports, with onset after stopping slightly more frequent than during treatment; no prevalence could be derived · pp. 1057, 1063
- Treatment evidence was limited to two uncontrolled retrospective studies (13 men, IIEF improvement after 12 months; 12 men, improvement at a 6-month follow-up) and single case reports (e.g. low-power laser, a dietary supplement). No guidelines exist, and the evidence was not sufficient to suggest a single approach · p. 1058, Table 2; p. 1060
- The authors found insufficient evidence to justify limiting SSRI prescriptions or stopping them early, and caution against routine early discontinuation; they note reports of improvement after SSRIs were restarted. They also state their findings support the EMA's caution about possible continued sexual disturbance after stopping · pp. 1054, 1063–1064
Limitations the authors note
- Restricted to English-language articles with full text available
- Some discrepancies with previous reviews, even allowing for publication dates
- High risk of bias in most included reports, so caution is needed in generalising to clinical practice
- Included studies had uncertain sampling criteria and little control for psychopathology and comorbidities; online surveys risk selection bias toward higher prevalence and lack clinical detail
Also worth weighing (library’s note)
- Narrative synthesis only; no numbers were pooled, and per-study risk-of-bias scores are given only in the online supplement (eContent-1)
- Two of the six "observational studies" (Healy 2018; Hogan 2014) are, per Table 3, the same dataset (Hogan being a less complete version, 120 accounts), so there are five separate observational datasets
- The text says post-SSRI PGAD was described only in women, only in case reports, and that there are no data on it in men, but Table 3 lists PGAD among symptoms reported by both men and women in the Healy 2018 website accounts
- The only prevalence-style figure in the tables, 12.6% (17 of 135; recomputed 12.6%) in Patacchini 2021, comes from a self-selected online survey
- On Embase and Google Scholar the search required the term "PSSD", so reports there not using it could be missed
- The two interventional studies are both in this corpus: "De Luca 2022" (LIT-029) and "Reisman 2021" (ref. 44, Reisman, Jannini TB and Jannini EA, J Mens Health 2022; LIT-030)
- The review reads the uncontrolled vortioxetine study as favouring an interplay between PSSD and depressive or anxious symptoms; that is the authors' interpretation
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sectors Interests: None declared
What it can support (library’s note): That, as of a December 2022 search, the clinical evidence on sexual dysfunction persisting after SSRIs (and on post-SSRI PGAD) consisted of a few small uncontrolled studies, surveys, pharmacovigilance reports and case reports at high risk of bias. It cannot support any estimate of how common the condition is, of causation, or of treatment effect.
Why it’s in the corpus
A 2023 systematic review of post-treatment sexual dysfunction evidence, covering literature to December 2022; documents exactly how sparse the literature is. Good "state of the evidence" anchor.
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