Is St. John's Wort (Hypericum perforatum) effective in reducing stress?

St. John's Wort for Stress Reduction

St. John's wort has not been proven effective specifically for stress reduction, though it shows efficacy for depression; its use should be approached with caution due to significant drug interactions and limited evidence for stress management. 1, 2

Efficacy for Stress vs. Depression

• St. John's wort (Hypericum perforatum) has been primarily studied for depression, not specifically for stress reduction 1
• Limited evidence from a 2011 animal study suggests St. John's wort may help alleviate stress-related memory impairment by restoring levels of synaptic plasticity proteins in the hippocampus and prefrontal cortex 2
• Another animal study showed St. John's wort administration prevented corticosterone-induced decrease in hippocampal cell proliferation, suggesting potential benefits in chronic stress models 3
• However, these findings are from preclinical animal studies and cannot be directly extrapolated to humans 2, 3

Evidence for Depression Treatment

• Low-quality evidence indicates St. John's wort may be as effective as second-generation antidepressants for treating major depressive disorder 1
• A 2017 meta-analysis of 27 clinical trials with 3,808 patients demonstrated comparable response and remission rates between St. John's wort and SSRIs for mild-to-moderate depression 4
• St. John's wort appears better tolerated than standard antidepressants, with lower discontinuation rates due to adverse events 1, 4

Important Safety Considerations

• St. John's wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), which can significantly decrease the effectiveness of many medications 5
• Major drug interactions include:
  • Reduced effectiveness of oral contraceptives, potentially leading to unintended pregnancy 5
  • Risk of serotonin syndrome when combined with SSRIs or MAOIs 5
  • Decreased plasma concentrations of HIV medications, anticonvulsants, and cancer treatments 5
• St. John's wort should be discontinued at least 2 weeks before surgery due to potential drug interactions 5

Quality Control Issues

• St. John's wort is not regulated by the FDA, with no standardization of content or potency in the United States 5, 1
• This lack of regulation creates challenges in determining appropriate dosing and ensuring product consistency 1

Common Adverse Effects

• Mild gastrointestinal symptoms, skin reactions, fatigue, sedation, dizziness, confusion, headache, and dry mouth have been reported 1
• Long-term safety data is limited as most studies range from only 4 to 12 weeks 4

Clinical Implications

• For patients seeking stress relief, cognitive behavioral therapy is a strongly recommended option with better evidence than herbal remedies 1
• If considering St. John's wort for stress-related symptoms that may overlap with depression, patients should:
  • Disclose all medications to healthcare providers to check for potential interactions 5
  • Be aware of the lack of standardization in available products 1
  • Understand that evidence specifically for stress reduction (rather than depression) is limited 2, 3