Gender effects in depression: Influence of HPA axis activity and steroid synthesis inhibitors

Whereas alterations of HPA axis activity in depression are largely independent from gender, the response to antidepressants like tricyclics seem to depend e.g. on the menopausal state. In the present study the steroid synthesis inhibitor metyrapone was compared to placebo in the treatment of severely depressed patients..

Methods: 33 women and 30 men were treated with standard antidepressants (fluvoxamine or nefazodone) for five weeks. From day 1 to day 21 either metyrapone or placebo was given in a double-blind randomized design. Psychopathological (HAMD, MADRS ratings) and hormonal measures were applied (corticotropin, cortisol).

Results: During placebo the overall antidepressant reponse was identical for both serotonergic compounds. Addition of metyrapone induced a significantly accelerated response from day 7 on. Regarding gender, male patients seem to respond more favourably already during placebo, but significantly during metryapone. Hormonal measures showed gender specific alterations.

Conclusions: Study designs with stratification of gender should be mandatory in treatment trials of depression, especially for compounds with impact upon HPA axis activity.