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With Comments from John La Puma, MD, FACP
April 2001; Volume 4; 47-48
Source: Woelk M. Comparison of St. John’s wort and imipramine for treating depression: Randomised controlled trial. BMJ 2000;321: 536-539.
To compare the efficacy and tolerability of Hypericum perforatum (St. John’s wort extract) with imipramine in patients with mild-to-moderate depression, we designed a randomized, multicentre, double-blind, parallel-group trial in 40 outpatient clinics in Germany. We recruited 324 outpatients with mild-to-moderate depression and randomized them to 75 mg imipramine bid or 250 mg hypericum extract ZE 117 bid for six weeks. We used the Hamilton depression rating scale, clinical global impression scale, and patient’s global impression scale as outcome measures.
Among the 157 participants taking hypericum, mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine, scores fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22/7 for the hypericum group and 2.42 for the imipramine group. On the seven-point self-assessments of global improvement completed by participants (1 = "very much improved;" 7 = "very much deteriorated") mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group.
None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatization subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the five-point scale used by participants to assess tolerability (1 = excellent tolerability; 5 = very poor tolerability) were better for hypericum (1.67) than imipramine (2.35).
Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. Four (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine.
This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild-to-moderate depression, but patients tolerate hypericum better.
The population in which St. John’s wort appears most effective is that of mildly depressed patients who are also anxious. Technically sound evidence for St. John’s wort’s equivalent effectiveness and better side effect profile than second-line antidepressants appears to be mounting. But the devil is in the details.
Many patients who might be candidates for St. John’s wort were purposefully excluded from this trial: those pregnant, breast feeding, premenopausal, and not using contraception; those with abnormal thyroid function or other relevant abnormalities on laboratory testing; and those with bipolar disorder, previous serious psychiatric disease, or history of alcohol or drug misuse. Plus, anyone who had taken any of the following medications within the past 14 days: monoamine oxidase inhibitors, antidepressants, lithium, antipsychotic drugs, neuroleptic drugs, cimetidine, oral corticosteroids, anticonvulsants, theophylline, or thyroid hormones.
The investigators also might have added oral contraceptives, antiviral/HIV agents, and transplant medications to the list: Negating effects of all of these have been clearly documented in the peer-reviewed medical literature within the past 12 months, and summarized here. (See Alternative Medicine Alert, September 2000, pp. 97-101.)
While this extract of St. John’s wort may be as effective and better tolerated than imipramine in a very narrowly defined population over the short term, St. John’s wort should not be recommended—disturbing emerging reports of untoward drug interactions, especially with other medications metabolized through the cytochrome p450 pathway, are increasingly noted.