Ben-Sheetrit · Annals of general psychiatry 2023 · retrospective cohort study · n=12,302

Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants.

Cited 21 times in the scientific literature.

Level 3 - non-randomized controlled study

Retrospective controlled cohort study using health maintenance organization electronic records.

PubMed 37085865 · doi:10.1186/s12991-023-00447-0 · record verified 2026-08-26

What was done

A 19-year retrospective cohort study analyzed 12,302 Israeli males aged 21–49 from a large HMO database. Inclusion required being a non-smoker with no medical or psychiatric comorbidities, no alcohol or substance use, and no medications associated with erectile dysfunction (ED). ED was defined by prescriptions for phosphodiesterase-5 inhibitors. Logistic regression compared serotonergic antidepressant (SA)-treated patients against non-treated controls, adjusting for age, BMI, socioeconomic status, depression, and anxiety.

What was found

SA exposure was significantly associated with ED in crude analyses (cOR = 3.6, 95% CI 2.8–4.8, p < 0.000001) and remained significant after multivariable adjustment (aOR = 3.2, 95% CI 2.3–4.4, p < 0.000001). The estimated risk for post-SSRI sexual dysfunction (PSSD) among SA-treated patients was 0.46% (1 in 216), with an overall prevalence of 4.3 per 100,000.

Why it matters

This study provides an initial quantitative estimate of the risk of persistent sexual dysfunction following serotonergic antidepressant use to guide patient informed consent.

Limits

The study is restricted to young-to-middle-aged males and evaluates only erectile dysfunction through a proxy measure (PDE-5 inhibitor prescriptions), excluding females, non-prescription ED, and other domains of sexual dysfunction like reduced libido or anorgasmia. Observational database design remains vulnerable to unmeasured confounding and misclassification.

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