Systematic reviews
A large number of systematic reviews and meta-analyses have been published on St John’s wort and have been summarised previously.(1) The Cochrane review of St John’s wort in depression published in 2005 concluded that ‘current evidence regarding hypericum extracts is inconsistent and confusing’ as several recent placebo-controlled trials suggested minimal beneficial effects in patients who met the criteria for depression while other trials suggested that hypericum and standard antidepressants had similar beneficial effects.(2) (see STOP PRESS below). The authors also highlighted the possible variability in pharmaceutical quality of preparations on the market and those included in the trials. Since this review was published, a number of trials have been published and are listed below under the heading RCTs as have several more reviews. One study involved a reanalysis of data from patients in the acute phase of mild depression from previous trials.(3) Over 200 patients of the original 1,200 patients had a Hamilton Rating Scale for Depression (HAMD) scores of 20 or less and were included in the re-analysis (3). The results indicated that St John’s wort leads to a substantial increase in the probability of remission in patients with mild depression.
Safety
Other systematic reviews have focused on safety of St John’s wort. Systematic reviews of safety published up to 2005 have been discussed previously (1). These concluded that the available evidence suggested that St John’s wort is, in general, well-tolerated although there have been case reports of adverse effects including allergy or photosensitivity and possible induction of manic episodes in susceptible individuals. The main safety concern is the potential to interact with other drugs and the list of those drugs likely to be affected is constantly being extended. Three of the systematic reviews found during this Evidence Update address safety, one focusing on safety in pregnancy and lactation (4), and two on drug interactions (5,6). See also articles listed in the safety section of Herbal Medicine and the updated Cochrane review (see Stop Press below).
STOP PRESS (8th October 2008)
An update of the Cochrane review has been published today. It now focuses on major depression and concludes that:
“The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.”
Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD000448. DOI: 10.1002/14651858.CD000448.pub3. [Full text] See also analysis from Behind the Headlines.
References:
- Pilkington K, Boshnakova A, Richardson J. St John's wort for depression: time for a different perspective? Complementary Therapies in Medicine. 2006, 14(4):268-81. [PubMed abtract]
- Linde K, Mulrow CD, Berner M, Egger M. St John's Wort for depression. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD000448. DOI: 10.1002/14651858.CD000448.pub2.
- Kasper S, Gastpar M, Muller WE, Volz HP, Dienel A, Kieser M, et al. Efficacy of St. John's wort extract WS 5570 in acute treatment of mild depression: a reanalysis of data from controlled clinical trials. European Archives of Psychiatry and Clinical Neuroscience. 2008, 258(1):59-63. [PubMed abstract]
- Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (Hypericum) during pregnancy and lactation. Canadian Journal of Clinical Pharmacology. 2006, 13(3):e268-e276. [Full text]
- Nieuwstraten C, Labiris NR, Holbrook A. Systematic overview of drug interactions with antidepressant medications. Canadian Journal of Psychiatry. 2006, 51:300-16. [PubMed abstract] [DARE provisional record]
- Zhou SF, Lai X. An update on clinical drug interactions with the herbal antidepressant St. John's wort. Current Drug Metabolism. 2008, 9(5):394-409. [PubMed abstract]
List of all relevant studies
Systematic reviews (and DARE appraisals)
Clement K, Covertson CR, Johnson MJ, Dearing K. St. John's wort and the treatment of mild to moderate depression: a systematic review. Holistic Nursing Practice. 2006, 20(4):197-203. [PubMed abstract] [DARE provisional record]
Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (Hypericum) during pregnancy and lactation. Canadian Journal of Clinical Pharmacology. 2006, 13(3):e268-e276. [Full text]
Jou HJ, Hsu IP, Ling PY, Huang HT, Lin CT, Wu SC. Extracts of St. John's wort for mild to moderate depression: a meta-analysis of randomized, double-blinded and placebo-controlled trials. Nutritional Sciences Journal. 2005, 30(4): 166-173. [DARE provisional record]
Kasper S, Gastpar M, Muller WE, Volz HP, Dienel A, Kieser M, et al. Efficacy of St. John's wort extract WS 5570 in acute treatment of mild depression: a reanalysis of data from controlled clinical trials. European Archives of Psychiatry and Clinical Neuroscience. 2008, 258(1):59-63. [PubMed abstract]
Linde K, Knuppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders: a systematic review. Phytomedicine. 2005, 12:148-57 [PubMed abstract] [DARE appraisal]
Linde K, Berner M, Egger M, Mulrow C. St John's wort for depression: meta-analysis of randomised controlled trials. British Journal of Psychiatry. 2005;186:99-107. [Full text] Duplicate publication of Cochrane review below.
Linde K, Mulrow CD, Berner M, Egger M. St John's Wort for depression. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD000448. DOI: 10.1002/14651858.CD000448.pub2. [Full text]
Nieuwstraten C, Labiris NR, Holbrook A. Systematic overview of drug interactions with antidepressant medications. Canadian Journal of Psychiatry. 2006, 51:300-16. [PubMed abstract] [DARE provisional record]
Zhou SF, Lai X. An update on clinical drug interactions with the herbal antidepressant St. John's wort. Current Drug Metabolism. 2008, 9(5):394-409. [PubMed abstract]
Randomized controlled trials (RCTs)
Anghelescu IG, Kohnen R, Szegedi A, Klement S, Kieser M. Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study. Pharmacopsychiatry. 2006, 39(6):213-9. [PubMed abstract]
Bjerkenstedt L, Edman GV, Alken RG, Mannel M. Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients. European Archives in Psychiatry and Clinical Neuroscience. 2005 Feb;255(1):40-7. [PubMed abstract]
Farabaugh A, Mischoulon D, Fava M, Wu SL, Mascarini A, Tossani E, et al. The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients. International Clinical Psychopharmacology. 2005 Mar;20(2):87-91. [PubMed abstract]
Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, et al. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. Journal of Clinical Psychopharmacology. 2005, 25(5):441-7. [PubMed abstract]
Gastpar M, Zeller K. [Comparison of hypericum extract STW3 and sertraline in the treatment of mode-rate depression: a double-blind randomized 24-week-study]. Psychopharmakotherapie. 2005, 12:146-53.
Gastpar M, Singer A, Zeller K. Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline. Pharmacopsychiatry. 2005, 38(2):78-86. [PubMed abstract]
Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. 2006 Mar;39(2):66-75. [PubMed abstract]
Kasper S, Dienel A, Kieser M. Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after successful acute treatment of mild to moderate depression--rationale and study design. International Journal of Methods in Psychiatric Research. 2004, 13(3):176-83. [PubMed abstract]
Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298]. BMC Medicine. 2006, 4:14. [Full text]
Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Placebo controlled continuation treatment with Hypericum extract WS 5570 after recovery from a mild or moderate depressive episode. Wiener Medizinische Wochenschrift. 2007, 157(13-14):362-6. [PubMed abstract]
Moreno RA, Teng CT, Almeida KM, Tavares JH. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sample. Revista Brasileira de Psiquiatria. 2006;28:29-32. [PubMed abstract]
Papakostas GI, Crawford CM, Scalia MJ, Fava M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hypericum perforatum versus fluoxetine. Neuropsychobiology. 2007;56(2-3):132-7. [PubMed abstract]
Randlov C, Mehlsen J, Thomsen CF, Hedman C, von FH, Winther K. The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia--a double-blind placebo-controlled study. Phytomedicine. 2006 Mar;13(4):215-21. [PubMed abstract]
Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ. 2005, 330(7490):503. [PubMed abstract] Erratum in: BMJ. 2005 Apr 2;330(7494):759. dosage error in text.
Uebelhack R, Gruenwald J, Graubaum HJ, Busch R. Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial. Advances in Therapy. 2004, 21(4):265-75. [PubMed abstract]
Other studies of interest (linked to RCTs)
Gelenberg AJ, Shelton RC, Crits-Christoph P, Keller MB, Dunner DL, Hirschfeld RM, et al. The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication. Journal of Clinical Psychiatry. 2004, 65(8):1114-9. [PubMed abstract]
Kieser M, Szegedi A. Predicting stable treatment response in patients with major depression treated with hypericum extract WS 5570/5572. Pharmacopsychiatry. 2005, 38(5):194-200. [PubMed abstract]
Lecrubier Y, Bech P. The Ham D(6) is more homogenous and as sensitive as the Ham D(17). European Psychiatry. 2007, 22(4):252-5. [PubMed abstract]
Mischoulon D, Schwartz F, Papakostas G, Farabaugh A, Cusin C, Nierenberg AA, et al. Characterization of the placebo response in the Hypericum Depression Trial Group's study. 46th Annual NCDEU Meeting; 2006 June 12-15; Boca Raton , FLorida. 2006, p. 265. [Abstract]
Vitiello B, Shader RI, Parker CB, Ritz L, Harlan W, Greenblatt DJ, et al. Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial. Journal of Clinical Psychopharmacology. 2005, 25(3):243-9. [PubMed abstract]
Murck H, Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, et al. Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo. International Journal of Neuropsychopharmacology. 2005, 8(2):215-21. [PubMed abstract]
Link back to 2008 Annual evidence update on CAM in depression
