Luteal phase administration of agents for the treatment of premenstrual dysphoric disorder

CNS Drugs. 2004;18(7):453-68. doi: 10.2165/00023210-200418070-00004.


This review focuses on current information about luteal phase administration (i.e. typically for the last 2 weeks of the menstrual cycle) of pharmacological agents for the treatment of premenstrual dysphoric disorder (PMDD). Compared with continuous administration, a luteal phase administration regimen reduces the exposure to medication and lowers the costs of treatment. Based on evidence from randomised clinical trials, SSRIs are the first-line treatment for PMDD at this time. Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration. Clinical trials of these agents and citalopram have demonstrated that symptom reduction is similar with both administration regimens. When used to treat PMDD, SSRI doses are consistent with those used for major depressive disorder. The medications are well tolerated; discontinuation symptoms with this intermittent administration regimen have not been reported. Other medications that have been examined in clinical trials for PMDD or severe premenstrual syndrome (PMS) using luteal phase administration include buspirone, alprazolam, tryptophan and progesterone. Buspirone and alprazolam show only modest efficacy in PMS (in some but not all studies), but there may be a lower incidence of sexual adverse effects with these medications than with SSRIs. Symptom reduction with tryptophan was significantly greater than with placebo, but the availability of this medication is strictly limited because of safety concerns. Progesterone has consistently failed to show efficacy for severe PMS/PMDD in large, randomised, placebo-controlled trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use
  • Breast Feeding
  • Clinical Trials as Topic
  • Drug Administration Schedule
  • Drug Tolerance
  • Female
  • Gonadal Steroid Hormones / physiology
  • Humans
  • Luteal Phase* / drug effects
  • Pregnancy
  • Premenstrual Syndrome / drug therapy*
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents
  • Gonadal Steroid Hormones
  • Serotonin Uptake Inhibitors
  • Serotonin