Does estrogen enhance the antidepressant effects of fluoxetine?

Background: While hormone replacement therapy (HRT) has not been shown to be an effective treatment for major depression, preliminary studies suggest that estrogen may potentiate the effect of selective serontonin reuptake inhibitors. Method: In an ongoing study, perimenopausal women diagnosed with major depression were randomly assigned to one of three treatment conditions: (1) fluoxetine 10–20 mg alone, (2) estradiol patch 0.1–0.2 mg alone or (3) the combination of fluoxetine 10–20 mg and estradiol patch 0.1–0.2 mg. Results: In the five cases presented here, the combination of fluoxetine and estradiol was most effective, followed by fluoxetine alone and then estradiol alone. Limitations: These are selected cases from an ongoing study and do not represent statistically significant data. Conclusions: These preliminary cases suggest that estrogen can enhance the efficacy of antidepressant medication in menopausal women and this adjunctive treatment strategy may be superior to antidepressant or estrogen alone. Further research is needed in elucidating the mechanisms by which estrogen may enhance antidepressant action in perimenopausal women.