St. John's Wort for Mild-to-Moderate Depression

Efficacy and Tolerability

The American College of Physicians recommends choosing between cognitive behavioral therapy or second-generation antidepressants as first-line treatment for mild-to-moderate depression, with St. John's wort considered for patients who cannot tolerate standard antidepressants 1, 2, 3, 4
St. John's wort has similar response rates to second-generation antidepressants (54% vs. 52%) and comparable remission rates (36% vs. 30%) in patients with mild-to-moderate depression 3
Patients on St. John's wort have significantly lower treatment discontinuation rates (12% vs. 16%) and discontinuation due to adverse events (4% vs. 7%) compared to those on antidepressants 3
Moderate-quality evidence confirms St. John's wort is better tolerated than second-generation antidepressants 1, 2, 5

St. John's wort is not regulated by the U.S. Food and Drug Administration, and its use is contraindicated with monoamine oxidase inhibitors or serotonin reuptake inhibitors due to serotonin syndrome risk 1, 2, 5, 6
St. John's wort may reduce the efficacy of oral contraceptives and immunosuppressants, and its use is not recommended for patients taking these medications 1, 2, 5, 6
St. John's wort decreases dasatinib plasma concentrations unpredictably in cancer patients 7

In older adults (aged 60-80 years), St. John's wort shows equal effectiveness and similar adverse event rates compared to second-generation antidepressants (low-quality evidence) 1, 2
St. John's wort might be considered for mild-to-moderate depression in patients who cannot tolerate standard antidepressants, have no contraindicated medications, and have access to quality-controlled European preparations 1, 2, 3, 6

The American College of Physicians recommends starting with 300 mg of standardized extract (0.3% hypericin) three times daily, totaling 900 mg/day, and continuing this dose for at least 4 weeks to assess response 8
If inadequate response after 4 weeks, the American College of Physicians suggests increasing to 1200 mg/day (400 mg three times daily) 8
The acute treatment phase should last a minimum of 6-12 weeks 8

Moderate-quality evidence confirms that St. John's wort has better tolerability than second-generation antidepressants, with discontinuation rates due to adverse events being significantly lower (4% vs 7% for SSRIs) 8
In older adults (60-80 years), the effectiveness and adverse event rates of St. John's wort are similar to SSRIs, though evidence quality is low 8