Treatment of premenstrual worsening of depression with adjunctive oral contraceptive pills: a preliminary report

J Clin Psychiatry. 2007 Dec;68(12):1954-62. doi: 10.4088/jcp.v68n1218.


Objective: Despite the efficacy of antidepres-sants, 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 >or= 15) and high late-luteal phase (Daily Rating of Severity of Problems scores) were randomly assigned to open-label ethinyl estradiol (EE) 30 mug/day plus drospirenone 3 mg/day (EE/DRSP) for 21 days and double-blinded treatment with EE 30 mug/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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androstenes / therapeutic use*
  • Antidepressive Agents / therapeutic use
  • Contraceptives, Oral / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Drug Therapy, Combination
  • Estradiol / blood
  • Estrogens / therapeutic use*
  • Ethinyl Estradiol / therapeutic use*
  • Female
  • Humans
  • Menstrual Cycle / psychology*
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Progesterone / blood
  • Severity of Illness Index
  • Treatment Outcome


  • Androstenes
  • Antidepressive Agents
  • Contraceptives, Oral
  • Estrogens
  • Mineralocorticoid Receptor Antagonists
  • Ethinyl Estradiol
  • Progesterone
  • Estradiol
  • drospirenone