What is the recommended dosing for St. John's wort (Hypericum perforatum) for anxiety or depression?

St. John's Wort Dosing for Depression and Anxiety

Direct Dosing Recommendation

For adults and children above 12 years with mild-to-moderate depression, the standard dose is 300 mg three times daily (900 mg total daily) of a standardized extract, though FDA-labeled preparations may use alternative dosing such as 10 drops orally 3 times daily for hypericin formulations. 1, 2

Evidence-Based Dosing Details

Standard Dosing Regimen

• Most clinical trials demonstrating efficacy used 900-1800 mg daily of standardized St. John's wort extract, typically divided into three doses 2, 3
• Studies showing comparable efficacy to SSRIs employed flexible dosing schedules ranging from 600-1800 mg/day over 4-12 weeks 2, 4
• Long-term safety data supports use of 500 mg daily for up to 1 year in mild-to-moderate depression 3

Critical Prescribing Considerations

St. John's wort should NOT be routinely recommended in the United States due to lack of FDA regulation, absence of standardized potency, and inability to reliably obtain preparations with proven effectiveness comparable to those used in European clinical trials. 5, 6

When St. John's Wort May Be Considered

St. John's wort might be appropriate only for highly selected patients who meet ALL of the following criteria:

• Mild-to-moderate depression only (not severe depression or high suicide risk) 6, 7, 2
• Cannot tolerate standard second-generation antidepressants 7
• Not taking any contraindicated medications (see absolute contraindications below) 5, 6, 8
• Access to quality-controlled European preparations (not readily available in U.S.) 7

Absolute Contraindications

Do NOT prescribe St. John's wort if the patient is taking:

• SSRIs or MAOIs (risk of serotonin syndrome) 5, 6, 8
• Oral contraceptives (reduced effectiveness, unintended pregnancy risk) 5, 6, 8
• Immunosuppressants (cyclosporine, tacrolimus - risk of transplant rejection) 5, 6, 8
• Warfarin (reduced anticoagulation, thrombotic risk) 6, 8
• HIV medications (protease inhibitors, NNRTIs) 6, 8
• Cancer medications (imatinib, dasatinib) 6, 8, 7
• Ivabradine (specifically contraindicated) 8

Mechanism of Drug Interactions

St. John's wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, which accelerates metabolism and elimination of substrate drugs, reducing their therapeutic effectiveness. 5, 6, 8

Guideline-Based First-Line Recommendation

The American College of Physicians strongly recommends choosing between cognitive behavioral therapy (CBT) or second-generation antidepressants as first-line treatment for major depressive disorder, NOT St. John's wort. 6, 7

This recommendation is based on:

• Moderate-quality evidence showing CBT and SGAs are similarly effective 5, 6
• Better standardization and predictability of FDA-approved treatments 5
• Lower relapse rates with CBT compared to pharmacotherapy 5

Efficacy Data (For Context Only)

While St. John's wort demonstrates comparable efficacy to SSRIs in clinical trials:

• Response rates: 54% (St. John's wort) vs. 52% (SSRIs) 7, 2
• Remission rates: 36% vs. 30% 7, 2
• Lower discontinuation rates: 12% vs. 16% 7
• Better tolerability (moderate-quality evidence) 5, 6, 7

Lack of Evidence for Anxiety

St. John's wort has NOT demonstrated efficacy for anxiety disorders, including obsessive-compulsive disorder, despite theoretical pharmacologic rationale. 4

A randomized controlled trial in OCD showed no significant difference between St. John's wort (600-1800 mg/day) and placebo on Yale-Brown Obsessive-Compulsive Scale scores 4

Special Populations

Older Adults

• In patients aged 60-80 years, St. John's wort shows equal effectiveness and similar adverse event rates compared to SGAs, though evidence quality is low 6

Children and Adolescents

• NICE guidelines actively recommend AGAINST use of St. John's wort in children and youth with depression 5
• FDA labeling permits use in children above 12 years, but guideline evidence does not support this 1, 5

Monitoring Requirements If Prescribed

If St. John's wort is used despite the above cautions:

• Monitor for at least 24-48 hours after discontinuation before starting SSRIs (serotonin syndrome risk) 8
• More frequent monitoring of drug levels or therapeutic effects for any interacting medications 6, 8
• Discontinue at least 2 weeks before surgery (multiple drug interactions, serotonin effects) 8
• Patients must disclose use to ALL healthcare providers before starting new medications 6, 8

Common Adverse Effects

Mild adverse effects associated with St. John's wort include:

• Gastrointestinal symptoms (most common) 5, 3
• Skin reactions and photosensitivity 5, 8
• Dizziness, confusion 5
• Fatigue, sedation 5
• Headache, dry mouth 5

Clinical Bottom Line

Given the lack of FDA regulation, unpredictable potency, extensive drug interactions, and availability of safer evidence-based alternatives (CBT, SSRIs), St. John's wort should NOT be routinely recommended for depression or anxiety in clinical practice. 5, 6 If a patient insists on using it, ensure comprehensive medication reconciliation, document all contraindications discussed, and consider this only for mild-to-moderate depression in patients without contraindicated medications.