St. John's Wort for Depression Treatment

Efficacy and Safety

Low-quality evidence shows that St. John's wort may be as effective as second-generation antidepressants for treating major depressive disorder, according to the American College of Physicians 1, 2
Moderate-quality evidence indicates St. John's wort is better tolerated than second-generation antidepressants, with lower discontinuation rates due to adverse events, as reported by the American College of Physicians 3, 4
St. John's wort is associated with important drug-drug interactions as it induces cytochrome P450 isoenzyme 3A4, which may reduce the bioavailability or efficacy of several medications, including oral contraceptives and immunosuppressants, according to the American College of Clinical Pharmacology 2, 6
The American College of Clinical Pharmacology recommends that St. John's wort is contraindicated in patients receiving monoamine oxidase inhibitors or serotonin reuptake inhibitors due to risk of serotonin syndrome 2, 6

The American College of Physicians notes that St. John's wort is not regulated by the U.S. Food and Drug Administration, and there is no current standard for contents and potency of St. John's wort preparations in the United States 2, 6
Adverse effects associated with St. John's wort include mild gastrointestinal symptoms, skin reactions, fatigue or sedation, dizziness or confusion, headache, and dry mouth, as reported by the American College of Physicians 2, 7

Cognitive behavioral therapy is a strongly recommended option with moderate-quality evidence for patients with severe depression, high suicidality risk, or taking contraindicated medications, according to the American Psychological Association 8