Sex Differences in Responses to Antidepressant Augmentations in Treatment-Resistant Depression

Abstract

Background: Women are nearly twice as likely as men to suffer from major depressive disorder. Yet, there is a dearth of studies comparing the clinical outcomes of women and men with treatment-resistant depression (TRD) treated with similar augmentation strategies. We aimed to evaluate the effects of the augmentation strategies in women and men at the McGill University Health Center.

Methods: We reviewed health records of 76 patients (42 women, 34 men) with TRD, treated with augmentation strategies including antidepressants (AD) with mood stabilizers (AD+MS), antipsychotics (AD+AP), or in combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Åsberg Depression Rating Scale (MADRS), Quick Inventory of Depressive Symptomatology (QIDS-C16), and Clinical Global Impression rating scale (CGI-S) at the beginning and after 3 months of an unchanged treatment. Changes in individual items of the HAMD-17 were also compared between the groups.

Results: Women and men improved from beginning to 3 months on all scales (P < .001, η p2 ≥ 0.68). There was also a significant sex × time interaction for all scales (P < .05, η p2 ≥ 0.06), reflecting a greater improvement in women compared with men. Specifically, women exhibited greater improvement in early (P = .03, η p2 = 0.08) and middle-of-the-night insomnia (P = .01, η p2 = 0.09) as well as psychomotor retardation (P < .001 η p2 = 0.16) and psychic (P = .02, η p2 = 0.07) and somatic anxiety (P = .01, η p2 = 0.10).

Conclusions: The combination of AD+AP/MS generates a significantly greater clinical response in women compared with men with TRD, supporting the existence of distinct pharmacological profiles between sexes in our sample. Moreover, they emphasize the benefit of augmentation strategies in women, underscoring the benefit of addressing symptoms such as insomnia and anxiety with AP and MS.

Keywords: Antidepressants; antipsychotics; major depressive disorder; mood stabilizers; treatment-resistant depression.

Figure 1.

Changes in scales in women (n = 42) vs men (n = 34) with treatment-resistant depression (TRD). Two-way ANOVAs with sex as between-subject factor and time as a within-subject factor, followed by Tukey post-hoc analyses. Δ scores are reported for women and men (mean within-group change from T0 to T3). CGI, Clinical Global Impression rating scale; MADRS, Montgomery-Åsberg Depression Rating Scale; QIDS, Quick Inventory of Depressive Symptomatology (Clinician-Rated). *P < .05, **P < .01, ***P < .001.