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Table 4 Trials testing St. John's wort

From: Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review

Reference Study Design Sample Population Intervention Control Length of Treatment Outcomes Direction of Evidence Reported Adverse Events
Taylor (2000) [63] Open-label; Uncontrolled; Observational 13 subjects with a primary DSM-IV diagnosis of OCD of at least 12 month duration Fixed dose of 900 mg/day of 0.3% hypericin (a psychoactive compound in Hypericum) N/A 12 weeks Significant improvement in Y-BOCS scores in SJW group (comparable to those seen in clinical trials with SSRIs). + Diarrhea
Restless sleep
Volz (2002) [61] Randomized; Double-blind; Parallel Group 149 outpatients diagnosed with somatization
Disorder2, undifferentiated somatoformDisorder3, or somatoform autonomic
Hypericum extract LI 160
(600 mg/day)
Placebo 6 weeks Significant reduction in anxiety (HAMA-SOM, CGI, HAMA-T, HAMA-PSY, HDS, SCL-90-R, SCL-90-R-ANX) in favour of SJW treatment. + Verywell tolerated.
Abdominal pain
Muller (2003) [62] Open-label; uncontrolled observational 500 patients diagnosed with depression comorbid with anxiety (1) 500 mg valerian extract5 and 600 mg/day St John's Wort6(2) 1,000 mg valerian extract7 and 600 mg/day St John's wort6 N/A 6 weeks Significant reduction in anxiety disorder symptoms (HAMA) in both treatment groups.
Higher dosage results in greater improvements.
+ Allergy
Bad dreams
Sleep disorders
Kobak (2005) [60] Randomized; Double-blind;Parallel Group 40 subjects with GAD St John's wort8; flexible dose (600-1800 mg/day), mean dose at week 12 was 1676 mg/day Placebo 12 weeks No significant difference to placebo (LSAS) - Similar to placebo.
Gastrointestinal upset
Kobak (2005) [59] Randomized;
Parallel Group
60 outpatients with primary diagnosis of OCD St John's wort LI 1608; flexible dose (600-1800 mg/day), mean dose at week 12 was 1663 mg/day Placebo 12 weeks No significant difference to placebo (Y-BOCS) - Similar to placebo9.
Gastrointestinal symptoms
Sleep disturbance
Sarris (2009) [51] Randomized; Double-blind; Crossover 28 adults with MDD and co-occurring anxiety Hypericum perforatum10
(1 × 1.8 g tablet, three times/day); Kava rhizome aqueous extract11(1 × 2.66 g tablet, 3 times/day)
Placebo 4 weeks Combination treatment had no significant effects on anxiety (BDI-II). - No serious adverse events.
Mild gastrointestinal upset.
No liver toxicity
  1. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, fourth edition; Y-BOCS: Yale-Brown Obsessive-Compulsive Scale; OCD: obsessive-compulsive disorder; GAD: generalized anxiety disorder; SJW: St John's wort; SCL-90-R-ANX: Self-Report Symptom Inventory-90 Items revised, subscore somatic anxiety; HAMA: Hamilton Anxiety Scale; ICD-10; International Classification of Diseases; LSAS: Liebowitz Social Anxiety Scale; HAMA-SOM: Hamilton Anxiety Scale, subscore somatic anxiety; CGI: Clinical Global Impressions; HAMA-PSY: Hamilton Anxiety Scale, subscore psychic anxiety; HAMA-T: Hamilton Anxiety Scale, total score; HDS: Hamilton Depression Scale; SCL-90-R: Self-Report Symptom Inventory-90 Items revised; PGI-I: Patient Global Impressions of Improvement; CGI-I: Clinical Global Impressions of Improvement; CGI-S: Clinical Global Impressions of Severity.
  2. 1. Clinician observation [case 1], SCL-90-R [case 2]; self-assessment, HAMA [case 3].
  3. 2. ICD-10: F45.0.
  4. 3. F45.1.
  5. 4. F45.3.
  6. 5. Euvegal Balance tablet; drug-extract-ratio 3-6:1.
  7. 6. Neuroplant tablet; drug-extract-ratio 2.5-5:1.
  8. 7. Euvegal Balance tablet.
  9. 8. Drug/extract ratio of 3-6:1.
  10. 9. Except agitation which was higher with SJW.
  11. 10. Standardized to 990 μg of hypericin, and 1500 μg of flavone glycosides.
  12. 11. Standardized to 50 mg of kavalactones.