Study 5

Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160

Au: Hänsgen-K-D, Vesper-J and Ploch-M

SO: J Geriatr Psychiatry Neurol 1994; (supl1) PP 15-18

Introduction

Previous placebo-controlled, double-blind trials of extract LI 160 have had a duration of 4 weeks, in keeping with the drug trial guidelines for antidepressants. In this study, the trial drug was given for 6 weeks. To enable this, the so-called observation group design was chosen, in which the patients in the placebo group are given the trial medication for the last 2 weeks of the study.

Description

72 patients, aged 18-70 years, with major depression according to DSM-III-R from a total of 11 neurology and psychiatry practices or general practices were given Jarsin 300 (0.9 mg total hypericin) or a placebo for 6 weeks. In weeks 5 and 6, patients in both groups took the trial medication.

Further inclusion criteria were a total score on the Hamilton Depression Scale (HAMD) of 16 or more and a duration of their depressive episode from 2 weeks to a maximum of 6 months.

Patient compliance was evaluated by counting the tablets returned at each follow-up point. Study participants were informed that all patients would receive the trial medication for at least 2 weeks during the course of the study.

Results

• The original placebo group improved in weeks 5 and 6 while on the trial medication, while the treatment group also continued to improve over the same period.
• The Hamilton responder rate (reduction of more than 50% in the baseline values, or final scores of less than 10) in week 4 was 81% in the treatment group and 26% in the placebo group.

HAMD score

• Figure 6 shows that the mean fell in the treatment group from a baseline value of 21.8 points to 9.3 points (within the normal range) after 4 weeks, with a further reduction to 6.3 points in weeks 5 and 6, while the placebo group failed to reach normal values. There is a statistically significant difference in this parameter after 2 and 4 weeks (treatment vs placebo, both p <.001).
• Subsequent treatment in the placebo group (weeks 5 and 6) also led to a reduction in symptoms, similar to the scaled changes seen in the treatment group in weeks 1 and 2 .

Depression scale (D-S)

• After 4 weeks of treatment with hypericum, normal values were achieved (mean and standard deviation). There were significant differences between groups in weeks 2 and 4 (both p< .001). Subsequent treatment of the placebo group with hypericum (weeks 5 and 6 led to reduction in symptoms, at least as great as those in the treatment group (weeks 1 and 2) when related to the scaled values.

BEB

• The level of symptoms according to the BEB fell in the treatment group from 131 to 89 in week 4 and to 77 in week 6, while in the placebo group it fell from 127 to 104 in week 4 and then, on the trial medication, to 85 points. The groups are different at the 1% level at weeks 2 and 4.
• Figure 7 shows the symptom profile obtained using the BEB in the treatment and placebo groups in week 4, and the overall baseline values. More significant changes are seen in the treatment group for well-being, cardiovascular symptoms, and anxiety/phobia symptoms. Well-being is particularly closely associated with a relief of depressive symptoms.
  was associated with a noticeable improvement in the placebo group.

CGI

• The severity of illness measured by Clinical Global Impressions (CGI) was much reduced after 4 weeks of treatment with the trial drug, with further improvement in the last 2 weeks.
• With the placebo, the severity diminished much less in the first 4 weeks. After that, however, taking the trial medication during the last two weeks

Side effects

One patient in the treatment group complained about sleep disturbance and two in the placebo group complained about gastrointestinal symptoms.

Researchers' comments

In interpreting the results, it must be borne in mind that the participants in the trial knew that they would receive the trial medication for at least 2 weeks. Most of the patients treated with the trial drug benefited from taking hypericum extract, as is shown by the continuous fall in depressive symptoms from the start of the study to the end of week 6 of treatment. Participants in the placebo group had no real improvement in symptoms up to the end of week 4.

Since the influence of certain doctors or practices are eliminated from the overall results because of the large number of practices supplying subjects, the results of a study such as this are particularly powerful. Because of its potent and specific efficacy with few or no side effects, hypericum extract LI 160 can be recommended as an antidepressant for treatment of depressed outpatients.