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Treatment of Premenstrual Worsening of Depression With Adjunctive Oral Contraceptive Pills: A Preliminary Report

Hadine Joffe, M.D., M.Sc.; Laura F. Petrillo, M.D.; Adele C. Viguera, M.D., M.P.H.; Hannah Gottshcall, B.A.; Claudio N. Soares, M.D., Ph.D.; Janet E. Hall, M.D.; and Lee S. Cohen, M.D.

Objective: Despite the efficacy of antidepressants, depression can break through premenstrually. Oral contraceptive pills (OCPs) stabilize reproductive hormones and treat premenstrual dysphoric disorder. Management of depression that breaks through premenstrually has not been studied.

Method: Women taking antidepressants with successfully treated depression, except during the late luteal phase (Montgomery-Asberg Depression Rating Scale [MADRS] score >= 15) and high late-luteal phase (Daily Rating of Severity of Problems scores) were randomly assigned to open-label ethinyl estradiol (EE) 30 microg/day plus drospirenone 3 mg/day (EE/DRSP) for 21 days and double-blinded treatment with EE 30 microg/day or placebo for days 22 through 28 of 2 cycles. Participants were recruited from community and psychiatry outpatient clinics and enrolled into this study in 2004-2005.

Results: Of 25 subjects who received EE/DRSP (N = 12 with EE and N = 13 with placebo), 21 completed treatment. For study completers, premenstrual MADRS (p = .0019) and Daily Rating of Severity of Problems scores (p = .0001) improved significantly in both groups. Outcome did not differ between groups.

Conclusion: This study provides preliminary evidence that addition of EE/DRSP ( EE) to antidepressants may treat premenstrual breakthrough of depression. Stabilizing hormone levels with EE/DRSP may provide an important therapeutic option for women taking antidepressants whose symptoms break through premenstrually.

(J Clin Psychiatry 2007;68:1954-1962)

Received April 16, 2007; accepted June 27, 2007. From the Department of Psychiatry (Drs. Joffe, Petrillo, Viguera, Soares, and Cohen and Ms. Gottshcall) and the Reproductive Endocrine Unit, Department of Medicine (Dr. Hall), Massachusetts General Hospital, Harvard Medical School, Boston.

Supported by a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (Dr. Joffe). Product support provided by Berlex Laboratories. Drs. Hall and Cohen contributed equally as senior authors.

Presented at the 158th annual meeting of the American Psychiatric Association; May 21-26, 2005; Atlanta, Ga.

Financial disclosure is listed at the end of this article.

Corresponding author and reprints: Hadine Joffe, M.D., M.Sc., Perinatal and Reproductive Psychiatry Program, Massachusetts General Hospital, 185 Cambridge St., 2nd Floor, Boston, MA 02114 (e-mail: