Estrogen Augmentation of Antidepressants in Perimenopausal Depression: A Pilot Study

Melinda L. Morgan, Ph.D.; Ian A. Cook, M.D.; Andrea J. Rapkin, M.D.; and Andrew F. Leuchter, M.D.

Objective: To investigate the effects of estrogen augmentation on mood and memory in women with perimenopausal depression who had experienced a partial response to antidepressant medications.

Method: In a double-blind, placebo-controlled trial, 17 subjects taking antidepressant medication were randomly assigned to either 0.625 mg/day of conjugated estrogen (N = 11) or matching placebo (N = 6) for 6 weeks. Women between the ages of 40 and 60 years with DSM-IV major depressive disorder (MDD) in partial remission who had been taking antidepressant medication for a minimum of 8 weeks and were experiencing 1 or more perimenopausal symptoms (hot flashes, night sweats, irregular periods, sleep disturbance, memory impairment) were recruited from the community. The primary outcome measures were the final scores for the Hamilton Rating Scale for Depression (HAM-D) and the Buschke Selective Reminding Test. Data were gathered from April 2002 to August 2003.

Results: Women receiving estrogen had a significantly larger decrease in HAM-D scores than women receiving placebo (t = 2.86, df = 15, p = .012). Group differences in tests of verbal memory were not significant, although improved scores in verbal memory were significantly correlated with a decrease in follicle-stimulating hormone (p = .021).

Conclusion: Short-term, low-dose estrogen augmentation of antidepressant medication was significantly associated with improved mood, but not memory, in perimenopausal women with MDD in partial remission.

(J Clin Psychiatry 2005;66:774-780)

Received Aug. 11, 2004; accepted Nov. 6, 2004. From the Laboratory of Behavioral Pharmacology, University of California Los Angeles Neuropsychiatric Institute and Hospital, Department of Psychiatry and Biobehavioral Sciences (Drs. Morgan, Cook, and Leuchter) and the Department of Obstetrics and Gynecology (Dr. Rapkin), David Geffen School of Medicine at University of California Los Angeles.

This work was supported in part by the Young Investigator's Award from the National Alliance for Research on Schizophrenia and Depression, Great Neck, N.Y. (Dr. Morgan), and by Research Scientist Development Award KO2-MH01165 (Dr. Leuchter), grant RO1-MH40705 (Dr. Leuchter), and Career Development Award KO8-MHO1483 (Dr. Cook) from the National Institute of Mental Health, Bethesda, Md. Duramed supplied study medication.

Portions of these data were preliminarily presented at the 156th annual meeting of the American Psychiatric Association, May 17-22, 2003, San Francisco, Calif., and the 43rd annual meeting of the New Clinical Drug Evaluation Unit, May 27-30, 2003, Boca Raton, Fla.

Dr. Cook has received grant/research support from Eli Lilly, Pfizer, and Aspect Medical Systems and has been on the speakers/advisory boards of Eli Lilly, Pfizer, Wyeth, and Forest. Dr. Leuchter has been a consultant to Aspect Medical Systems; has received grant/research support from Bristol-Myers Squibb, Eli Lilly, and Pfizer; and has been on the speakers/advisory boards of Eli Lilly and Wyeth-Ayerst.

Corresponding author and reprints: Melinda L. Morgan, Ph.D., UCLA Neuropsychiatric Institute, 760 Westwood Plaza, Suite 37-439, Los Angeles, CA 90024-1759 (e-mail: melinda@ucla.edu).