St. John's Wort for Depression and Anxiety

Primary Recommendation

The American College of Physicians recommends choosing between cognitive behavioral therapy (CBT) or second-generation antidepressants as first-line treatment for major depressive disorder (strong recommendation, moderate-quality evidence) 2
St. John's wort is as effective as second-generation antidepressants (SSRIs) for treating mild-to-moderate depression, with better tolerability, but should only be used in carefully selected patients due to significant drug interactions and lack of FDA regulation in the United States 1, 2, 3

St. John's wort demonstrates equivalent response rates and remission rates compared to SSRIs in patients with mild-to-moderate depression 1, 4
Low-quality evidence from 9 trials showed no difference in response or remission when comparing St. John's wort with second-generation antidepressants after 4 to 12 weeks of treatment 1, 4

St. John's wort is absolutely contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or serotonin reuptake inhibitors (SSRIs) due to risk of serotonin syndrome 2, 3, 6, 5
St. John's wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, which significantly decreases plasma concentrations and effectiveness of many medications 2, 6, 5
Oral contraceptives: St. John's wort reduces effectiveness, potentially leading to unintended pregnancy 2, 3, 6
Immunosuppressants: May reduce efficacy of cyclosporine and tacrolimus, risking transplant rejection 2, 3, 6
Anticoagulants: Reduces warfarin effectiveness, increasing thrombotic risk 6
Cardiovascular medications: Decreases levels of statins and digoxin 6
Cancer medications: Unpredictably decreases dasatinib and imatinib plasma concentrations 3, 6
Anticonvulsants: May decrease levels of carbamazepine, phenytoin, and phenobarbital 6
HIV medications: Significantly decreases plasma concentrations of protease inhibitors and non-nucleoside reverse transcriptase inhibitors 6

St. John's wort is not regulated by the U.S. Food and Drug Administration, and there is no standardization of content or potency in preparations available in the United States 2, 6, 5

In older adults (aged 60-80 years), St. John's wort shows equal effectiveness and similar adverse event rates compared to second-generation antidepressants, though this is based on low-quality evidence 3

Patients taking St. John's wort with any interacting medications require more frequent monitoring of drug levels or therapeutic effects 6
Monitor for at least 24-48 hours after discontinuing St. John's wort, as symptoms of serotonin syndrome can emerge during this period if transitioning to SSRIs 6
Patients should always disclose use of St. John's wort to all healthcare providers, particularly before starting new medications or undergoing surgical procedures 6