A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder.
OBJECTIVE
This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine.


METHODS
After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate.


RESULTS
One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated.


CONCLUSIONS
St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.
Fava
Maurizio
M
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. mfava@partners.org
Alpert
Jonathan
J
Nierenberg
Andrew A
AA
Mischoulon
David
D
Otto
Michael W
MW
Zajecka
John
J
Murck
Harald
H
Rosenbaum
Jerrold F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D020902:Hypericum; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy / Q000009:adverse effects; D010936:Plant Extracts / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales
D018687:Antidepressive Agents, Second-Generation; D010936:Plant Extracts; D005473:Fluoxetine