A Preliminary Study of Luteal Phase Versus Symptom-Onset Dosing With Escitalopram for Premenstrual Dysphoric Disorder

Ellen W. Freeman, Ph.D.; Steven J. Sondheimer, M.D.; Mary D. Sammel, Sc.D.; Tahmina Ferdousi, Ph.D.; and Hui Lin, M.S.

Objective: This preliminary study compared the efficacy and tolerability of escitalopram administered at symptom onset or throughout the luteal phase in premenstrual dysphoric disorder (PMDD).

Method: Twenty-seven women meeting DSM-IV criteria for PMDD were randomly assigned in a double-blind manner to luteal phase (N = 13) or symptom-onset (N = 14) dosing of escitalopram (10-20 mg/day) for 3 consecutive menstrual cycles. Participants were enrolled from November 2002 to July 2003, and data collection was completed in December 2003. Symptoms were assessed using the 17-item Penn Daily Symptom Report (DSR), the Clinical Global Impressions-Improvement scale, the Hamilton Rating Scale for Depression, and the Sheehan Disability Scale. Scores were compared using repeated measures analysis of covariance and t statistics.

Results: Luteal phase and symptom-onset groups received escitalopram for a mean of 13.5 and 6.0 days, respectively (mean ± SD dose = 15.2 ± 5.1 mg/day at the third treatment cycle). Total premenstrual DSR scores significantly improved from baseline (p = .003), with a 57% decrease in the luteal phase group and a 51% decrease in the symptom-onset group. Clinical improvement (DSR score decrease >= 50% from baseline) was reported by 11 of 13 patients in the luteal phase group and 9 of 14 patients in the symptom-onset group. Symptom severity differentiated the response in the symptom-onset group, with those having more severe symptoms less likely to respond. Symptom severity did not differentiate treatment response to luteal phase dosing. Escitalopram was well tolerated. Adverse events were mild and transient, with only 2 patients discontinuing due to adverse events related to the medication.

Conclusion: Premenstrual dysphoric disorder improved significantly with either luteal phase or symptom-onset dosing of escitalopram. Women with more severe PMDD may respond better to luteal phase dosing than symptom-onset dosing.

(J Clin Psychiatry 2005;66:769-773)

Received Dec. 10, 2004; accepted Feb. 14, 2005. From the Department of Obstetrics and Gynecology (Drs. Freeman and Sondheimer), the Center for Clinical Epidemiology and Biostatistics (Dr. Sammel), and the Center for Research in Reproduction and Women's Health (Dr. Ferdousi and Ms. Lin), University of Pennsylvania Medical Center, Philadelphia.

The study was supported by a grant from Forest Laboratories, New York, N.Y.

Presented at the 44th annual New Clinical Drug Evaluation Unit meeting; June 1-4, 2004; Phoenix, Ariz.

Dr. Freeman has received grant/research support from Forest, Pfizer, Eli Lilly, GlaxoSmithKline, Berlex, Pherin, and Wyeth; has received honoraria from Forest, Pfizer, Wyeth, Berlex, Pherin, Warner-Chilcott, and Ortho-McNeil; and has participated in speakers/advisory boards for Pfizer, Warner-Chilcott, Ortho-McNeil, Wyeth, and Berlex. Dr. Sondheimer has received grant/research support from Forest and Pfizer and has participated in speakers/advisory boards for Pfizer. Drs. Sammel and Ferdousi and Ms. Lin report no other financial relationship relevant to the subject of this article.

The authors thank the study coordinators, Susan M. Dowd, M.S.N., C.R.N.P., and Naseem D. S. Kerr, M.P.H., and the staff of the PMS Program for their assistance.

Corresponding author and reprints: Ellen W. Freeman, Ph.D., Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, 3701 Market St., Mudd Suite 820, Philadelphia, PA 19104 (e-mail: freemane@mail.med.upenn.edu).