Sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants: secondary analyses of the GENPOD trial

Marilia Gougoulaki, Glyn Lewis, David Nutt, TJ Peters, Nicola J Wiles, Gemma Lewis*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review


Background: Differences in serotonergic neurotransmission could lead to sex differences in depressive symptoms and tolerability after treatment with SSRIs.

Aims: We investigated whether women have greater reductions in depressive symp-toms than men after treatment with an SSRI (citalopram) compared with a NaRI (re-boxetine) control, and after antidepressant treatment irrespective of class. We also investigated tolerability and the influence of menopausal status.

Methods: Secondary analyses of the GENPOD trial. 601 people with depression were recruited from UK primary care and randomised to citalopram or reboxetine. BDI-II score at 6 weeks was the primary outcome. Secondary outcomes included BDI-II score at 12 weeks, and physical symptoms and treatment discontinuation. We calculated main effects and interaction terms using linear and logistic regression models.

Results: There was no evidence that women experienced greater reductions in de-pressive symptoms than men, when treated with citalopram compared with reboxe-tine. We also found no evidence of sex differences at 6 or 12 weeks (irrespective of antidepressant class): men scored -0.31 (95% CI -2.23 to 1.62) BDI-II points lower than women at 6 weeks and -0.44, (95% CI -2.62 to 1.74) points lower at 12 weeks. There was no evidence of sex differences in physical symptoms or treatment discon-tinuation and no evidence for an influence of menopausal status.

Conclusion: Citalopram was not more effective in women compared with men and there was no difference in tolerability. Women and men had similar prognosis after SSRI treatment and similar prognosis regardless of antidepressant class. Findings were unaltered by menopausal status.
Original languageEnglish
JournalJournal of Psychopharmacology
Publication statusAccepted/In press - 15 Dec 2020


  • antidepressants
  • sex differences
  • depression

Cite this