The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo

Abstract

This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John's Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John's Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John's Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.

Figure 1

Patient Flow Chart 12-Week Study of St. John’s Wort vs. Citalopram vs. Placebo for Treatment of Minor Depression a. Reasons for termination after randomization but before returning for any post-randomization visit are as follows: St. John’s Wort: 2 due to protocol violations (not taking meds as prescribed) and 1 lost to follow-up; Citalopram: 1 due to adverse events (9 of them, continuing since screening) and 1 withdrew consent; Placebo: 2 lost to follow-up. b. 1 subject in the citalopram group had information on adverse events but no post-randomization visit data. c. Reasons for termination during acute treatment phase are as follows: St. John’s Wort: 1 adverse event (became MDD), 1 felt well and decided to stop, 1 had time constraints, 1 lost to follow-up; Citalopram: 4 due to adverse events (1 gastrointestinal, 1 severe agitation, 1 ringing in ears, and 1 fatigue & headaches), 1 due to time constraints associated with new job, and 1 lost to follow-up; Placebo: 2 due to adverse events (1 sexual side effects, and 1 “wiped out” and “fuzzy headed”), 1 due to insufficient clinical response, and 1 “PCP advised against continuing in study.”