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

Abstract

Background: Differences in serotonergic neurotransmission could lead to sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitors (SSRIs). Aims: We investigated whether women have greater reductions in depressive symptoms than men after treatment with an SSRI (citalopram) compared with a noradrenaline reuptake inhibitor (reboxetine) control, and after antidepressant treatment irrespective of class. We also investigated tolerability and the influence of menopausal status. Methods: Secondary analyses of the GENPOD (GENetic and clinical Predictors Of treatment response in Depression) trial. Six hundred and one people with depression were recruited from UK primary care and randomized to citalopram or reboxetine. Beck Depression Inventory (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 depressive symptoms than men when treated with citalopram compared with reboxetine. We also found no evidence of sex differences at six or 12 weeks (irrespective of antidepressant class): men scored −0.31 (95% confidence interval (CI) −2.23 to 1.62) BDI-II points lower than women at six 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 discontinuation 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.