A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria

Biol Psychiatry. 1999 Feb 1;45(3):313-20. doi: 10.1016/s0006-3223(98)00005-5.


Background: Antidepressant drugs, including specific serotonin reuptake inhibitors, have been shown to be beneficial in the treatment of premenstrual dysphoric disorders. The present study tests the efficacy of L-tryptophan, which acts specifically on serotonergic neurons, in this disorder.

Methods: In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day, and 34 were given placebo. The treatments were administered under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive menstrual cycles.

Results: The Visual Analogue Scales (VAS) revealed a significant (p = .004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items of dysphoria, mood swings, tension, and irritability. The magnitude of the reduction from baseline in maximum luteal phase VAS-mood scores was 34.5% with L-tryptophan compared to 10.4% with placebo.

Conclusions: These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle has a beneficial effect in patients with premenstrual dysphoric disorder.

Publication types

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

MeSH terms

  • Adult
  • Affective Symptoms / prevention & control*
  • Analysis of Variance
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Depression / prevention & control
  • Dizziness / chemically induced
  • Double-Blind Method
  • Female
  • Humans
  • Irritable Mood / drug effects
  • Placebos
  • Premenstrual Syndrome / drug therapy*
  • Quality of Life
  • Serotonin Agents / adverse effects
  • Serotonin Agents / therapeutic use*
  • Treatment Outcome
  • Tryptophan / adverse effects
  • Tryptophan / therapeutic use*


  • Antidepressive Agents, Second-Generation
  • Placebos
  • Serotonin Agents
  • Tryptophan