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Efficacy and tolerability of St John's wort in moderate to severe depression
Hypericum extract (St John's wort) is as effective in the acute treatment of patients with mild to moderate depression as treatment with certain tricyclic antidepressants or fluoxetine, moreover it is better tolerated than synthetic compounds. The efficacy of St John's wort in more severe depression has not, however, been clearly demonstrated. Therefore the efficacy of hypericum extract WS 5570 has been recently compared with paroxetine in patients with moderate to severe major depression.
A sample of 251 male and female outpatients in 21 psychiatric primary care centres was enrolled in a randomised double blind, double dummy, reference controlled, multicentre non-inferiority trial. All participants were 18-70 years old and had single or recurrent moderate or severe episodes of unipolar major depression with a total score
³ 22 points on the 17-item Hamilton depression scale. A group of 125 patients were assigned to hypericum extract 300 mg three times a day and 126 to paroxetine 20 mg once a day for six weeks. Doses were doubled after two weeks of treatment in patients whose total depression score had not decreased by at least 20%. The primary outcome measure was change in score on Hamilton depression scale from baseline to day 42. Change in scores on Montgomery-Åsberg depression rating scale, clinical global impressions, and Beck depression inventory were secondary measures.
After 42 days, the Hamilton depression scores decreasd by 14.4 points in the hypericum group and 11.4 points in the paroxetine group, which corresponded to 57% and 45% of the baseline value, respectively. Response rates were 71% and 60% in the hypericum group and in the paroxetine group, respectively. Remission rates were 50% and 35% in patients treated with hypericum and paroxetine, respectively. Both the intention to treat analysis and the per protocol analyses showed non-inferiority of hypericum and statistical superiority over paroxetine. All secondary measures showed differences between treatment groups in favour of hypericum. Patients treated with hypericum (55%) reported 172 adverse events while those receiving paroxetine (76%) reported 269.
These results show that hypericum extract, WS 5570, is at least as effective as paroxetine in ameliorating the symptoms of moderately or severely depressed patients and, since it is well tolerated, this support its use as an interesting alternative option in some fragile depressed populations.
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 Feb 2005, Online First, 10.1136/bmj.38356.655266.82.

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