Szegedi A, et al. 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.
A total of 251 patients with acute major depression were given either 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine, an SSRI, once a day for six weeks. At two weeks, the doses were increased to 1800 mg/day of hypericum and 40 mg paroxetine for patients who did not respond to the treatments. Researchers found that both the treatment groups showed significant decrease in depression scores. St. John's wort appears to be as effective as paroxetine in the management of severe depression. However, care should be taken while taking St. John's wort as it can interact with other drugs.
Fava M, et al. A double-blind, randomized trial of St John’s wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005;25:441–447.
Kasper S, et al. Continuation and long-term maintenance treatment with Hypericum extract WS((R)) 5570 after recovery from an acute episode of moderate depression - A double-blind, randomized, placebo controlled long-term trial. Eur Neuropsychopharmacol. Nov 2008;18(11):803-813.
St. John’s wort extract vs fluoxetine and placebo was evaluated in this double-blind trial. After single-blind washout, 135 patients with major depressive disorder were randomized to 12 weeks of therapy with St. John’s wort extract 900 mg/d, fluoxetine 20 mg/d, or placebo. HAMD-17 and analysis of covariance (ANCOVA) compared differences in endpoint HAMD-17 scores across the 3 treatment groups, treating baseline HAMD-17 as the covariate. ANCOVA analyses showed lower mean HAMD-17 scores at endpoint for St. John’s wort (n = 45; mean ± SD, 10.2 ± 6.6) vs fluoxetine group (n = 47; 13.3 ± 7.3; p < 0.03) with a trend toward same relative to placebo (n = 43; 12.6 ± 6.4; p = 0.096). There was also a trend toward higher rates of remission with St. John’s wort (38%) compared with fluoxetine (30%) and placebo (21%). Investigators found St. John’s wort to be safe and well tolerated and significantly more effective than fluoxetine with a trend toward superiority over placebo. Authors also conclude that the smaller than planned sample size may account for the lack of statistically significant advantage of St. John’s wort over placebo.
To determine the long-term effects of sustained treatment with hypericum extract WS 5570 in 426 individuals with recurrent, moderate depression (defined as Hamilton Depression Rating Scale [HAMD] total score ≥20 and ≥3 previous episodes in 5 years), this double-blind, randomized, placebo-controlled study was performed. Participants were given WS 5570 (3x300 mg/day) or placebo for 26 weeks during which relapse rates, time to relapse, HAMD scores, as well as adverse events were assessed. Time until relapse was significantly greater and HAMD scores were lower in the WS 5570-treated group as compared with the placebo group. Also, there was no difference in adverse events reported between the 2 groups. Thus, in individuals treated for recurrent, moderate depression, WS 5570 maintenance therapy reduced relapse; however, further studies are required to determine if WS 5570 maintenance therapy is comparable to conventional maintenance therapies.
Gastpar M, et al. 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;39:66-75.
This double-blind, placebo-controlled, multicentre phase III trial enrolled 388 patients suffering from moderate depression. Participants were randomized to one of 3-arms: hypericum extract 900 mg, citalopram 20 mg, or placebo using a once-daily dosage regimen for 6 weeks. The course of depression was documented using the HAMD, von Zerssen’s Adjective Mood Scale (BfS), and the Clinical Global lmpression (CGI) scales for safety and tolerability. HAMD scores demonstrated statistically significant therapeutic equivalence for hypericum extract vs citalopram (both 10.3 ± 6.4, p < 0.0001) as well as superiority over placebo (13.0 ± 6.9, p < 0.0001). At treatment end, 54.2 % of participants using hypericum extract were deemed therapy responders vs 55.9% citalopram and 39.2% placebo. Significantly more adverse events were documented for citalopram (53.2%, vs hypericum 17.2% and placebo 30%). Investigators concluded that hypericum extract was noninferior to citalopram, significantly superior to placebo, and had better safety and tolerability than citalopram.
Singer A, et al. Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: a reanalysis of data from a controlled clinical trial. Phytomedicine. 2011;18:739-42.
This reanalysis of the Gastpar et al study (above) evaluated duration of response and relapse/recurrence. In 30 of 154 responders (19.5%), relapse was highest with citalopram (14 of 54), and lowest with hypericum extract (8 of 54) and placebo (8 of 46) groups. No differences in relapse severity were observed. Response duration was longest with hypericum (1817 days, vs citalopram, 1755 days; placebo, 802 days). The authors determined that hypericum extract was more efficient in lowering relapse/recurrence rates of responders and increased response duration compared with citalopram and placebo.