What is the recommended dosage of St. John's Wort (Hypericum perforatum) for treating mild to moderate depression?

Recommended Dosage for St. John's Wort for Depression

For treating mild to moderate depression, St. John's wort should be taken at a dosage of 300-900 mg daily of a standardized extract containing 0.12% to 0.28% hypericin, divided into three doses. 1

Dosage Guidelines

The effective dosage range for St. John's wort in treating depression is based on clinical evidence:

• Standard dosage range: 300-900 mg daily, typically divided into three doses 1
• Most common effective dosage: 900 mg daily (300 mg three times daily) 1
• Standardization: Products should be standardized to contain 0.12% to 0.28% hypericin 1
• Duration: Clinical trials have evaluated effectiveness over 6-12 weeks 1, 2

Efficacy and Comparison to Prescription Antidepressants

St. John's wort has demonstrated effectiveness comparable to second-generation antidepressants (SGAs) for mild to moderate depression:

• Meta-analyses show similar response rates between St. John's wort (54%) and SGAs (52%) 1
• Remission rates are comparable (36% for St. John's wort vs. 30% for SGAs) 1
• St. John's wort has significantly lower discontinuation rates (12% vs. 16%) and fewer adverse events (4% vs. 7%) compared to SGAs 1

Important Considerations and Precautions

Quality and Standardization Issues

• St. John's wort is not regulated by the FDA, leading to potential variability in product quality and potency 1
• Look for products standardized to hypericin content (0.12-0.28%) 1
• Hyperforin (not hypericin) is now believed to be the primary constituent responsible for antidepressant effects 3

Drug Interactions (CRITICAL)

St. John's wort has significant drug interactions that must be considered:

• Induces cytochrome P450 isoenzyme 3A4, affecting metabolism of many medications 1
• Contraindicated with:
  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Triptans (risk of serotonin syndrome)
  • Oral contraceptives (reduced effectiveness)
  • Immunosuppressants (especially cyclosporine)
  • Anticoagulants (warfarin)
  • Anticonvulsants
  • Digoxin
  • HIV protease inhibitors
  • Theophylline 1, 3

Common Side Effects

• Gastrointestinal symptoms
• Dizziness/confusion
• Fatigue/sedation
• Photosensitivity (rare but potentially serious) 1, 4

Patient Selection and Monitoring

St. John's wort may be most appropriate for:

• Patients with mild to moderate depression
• Those who prefer a natural approach or cannot tolerate SGAs
• Patients not taking medications with potential interactions

Not recommended for:

• Severe depression (insufficient evidence)
• Patients with high suicidality or suicide risk 2
• Patients taking medications with known interactions

Duration of Treatment

• Clinical trials have only evaluated St. John's wort for 4-12 weeks 2
• Long-term safety and efficacy data are limited
• Regular monitoring is recommended if treatment extends beyond 12 weeks

Bottom Line

St. John's wort at 300-900 mg daily (standardized to 0.12-0.28% hypericin) is an effective option for mild to moderate depression with fewer side effects than conventional antidepressants. However, significant drug interactions and product standardization issues require careful consideration and monitoring.