Adverse neuropsychiatric reactions to herbal and over-the-counter "antidepressants"

J Clin Psychiatry. 2000 Nov;61(11):815-20. doi: 10.4088/jcp.v61n1102.


Background: Many unregulated over-the-counter agents for the treatment of depression are now available to patients and consumers. The potential for adverse neuropsychiatric effects with these agents has not been systematically studied in most cases.

Data sources: The author performed a MEDLINE search on a variety of herbal and nonherbal over-the-counter agents said to be useful in the treatment of depression. The Physicians' Desk Reference for Herbal Medicines was also consulted.

Data synthesis: Although many of the herbal agents said to have benefits in depression appear to be safe, serious neuropsychiatric side effects and interactions have been reported for several over-the-counter "antidepressants." There is reason to suspect underreporting of those adverse events. Moreover, there is very little evidence from systematic studies regarding the potential for drug-drug or herb-drug interactions with these over-the-counter agents. Vitamins and amino acids touted for the treatment of depression are also not without risk.

Conclusion: Although some over-the-counter remedies for depression are probably safe and effective for as-yet unidentified subgroups of depressed individuals, more research is required before these agents can be recommended for routine use. Stricter U.S. Food and Drug Administration oversight of these agents is indicated.

Publication types

  • Review

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / pharmacokinetics
  • Antidepressive Agents / therapeutic use
  • Dehydroepiandrosterone / adverse effects
  • Dehydroepiandrosterone / therapeutic use
  • Depressive Disorder / drug therapy*
  • Drug Information Services
  • Drug Interactions
  • Humans
  • Hypericum / adverse effects*
  • Hypericum / therapeutic use
  • Inositol / adverse effects
  • Inositol / therapeutic use
  • Mental Disorders / chemically induced*
  • Mental Disorders / diagnosis
  • Mental Disorders / epidemiology
  • Nonprescription Drugs / adverse effects*
  • Nonprescription Drugs / pharmacokinetics
  • Nonprescription Drugs / therapeutic use
  • Phytotherapy
  • Plants, Medicinal / adverse effects*
  • Plants, Medicinal / therapeutic use
  • Psychoses, Substance-Induced / diagnosis
  • Psychoses, Substance-Induced / epidemiology
  • Psychoses, Substance-Induced / etiology
  • S-Adenosylmethionine / adverse effects*
  • S-Adenosylmethionine / therapeutic use


  • Antidepressive Agents
  • Nonprescription Drugs
  • Dehydroepiandrosterone
  • Inositol
  • S-Adenosylmethionine