St. John's wort extract LI160 for the treatment of depression with atypical features - a double-blind, randomized, and placebo-controlled trial.
Mannel M , et al.
«Preliminary data suggest that hypericum extract LI160 is effective in atypical depression. Reported is the outcome of an 8-week double-blind, placebo-controlled, randomized trial of 600 mg LI160 vs. placebo in patients with vegetative features of atypical depression, i.e. hyperphagia or hypersomnia. One-hundred (100) patients with mild and 100 patients with moderate severity of a major depression according to ICD-10 were randomized. Patients needed to meet a score of 2 in at least one of the items 22-26 of the Hamilton-Depression-Rating-Scale (HAM-D) 28-item version and episode duration of at least 3 months. The primary outcome variable was the relative change of the HAM-D(17) from Baseline. Secondary outcome variables were the depression sub-score of the Patient Health Questionnaire (PHQ-9), the Clinical Global Impression (CGI), a patient's satisfaction scale, the Hamilton-Anxiety-Scale (HAM-A) and the sum score of atypical vegetative symptoms of the HAM-D(28). The percentage reduction of the HAM-D(17) for LI160 compared to placebo approached statistical significance (p=0.051) in the Full Analysis Set (FAS)-population. Using the conventional criterion of the absolute reduction of the HAM-D(17) significance was achieved (p<0.05). No significant benefit could be observed for the sum score of the atypical vegetative items of the HAM-D(28;) however, the sum score of the hypersomnia items (items 22-24) showed a significant superiority for LI160. The HAM-A, PHQ-9, and CGI-I scales demonstrated superiority of LI160 (p<0.01). Confining the analysis to moderately depressed patients, a highly significant benefit for the primary outcome variable was revealed. The study supports the beneficial effect of LI160 in depression with atypical features and the validity of the definition of atypical depression on the basis of reversed vegetative signs. Further, it identifies the PHQ-9 as a useful outcome variable in this population.»
Adolescent, Adult, Aged, Antidepressive Agents, Depression, Depressive Disorder, Double-Blind Method, Female, Humans, Hypericum, Male, Middle Aged, Plant Extracts, Psychiatric Status Rating Scales, Statistics, Nonparametric, Time Factors, Young Adult
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Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans.
Brockmöller J , et al.
«Extracts of St. John's wort (Hypericum perforatum) are used in treatment of depression. They contain various substances with the naphthodianthrones hypericin and pseudohypericin as characteristic ingredients. These compounds were shown to cause phototoxicity in cell culture and in animals. A placebo-controlled randomized clinical trial with monitoring of hypericin and pseudohypericin plasma concentration was performed to evaluate the increase in dermal photosensitivity in humans after application of high dose hypericum extracts. The study was divided into a single dose and a multiple dose part. In the single dose period, each of 13 volunteers received in a double blind fourfold complete crossover design, either placebo, or 900, 1800 or 3600 mg of a standardized hypericum extract (LI 160) containing zero, 2.81, 5.62 and 11.25 mg of total hypericin (total hypericin is the sum of hypericin and pseudohypericin). Maximum total hypericin plasma concentration were observed about 4 h after dosage and were 0, 0.028, 0.061 and 0.159 mg/L, respectively. Before and 4 h after drug intake, the subjects were exposed at small areas of their back to increasing doses of solar simulated irradiation (SSI, with combined ultraviolet A, UV-A, and UV-B light) and another part was exposed to selective UV-A light irradiation. Minimal erythema dose was determined 5, 20 and 68 h after irradiation. Comparison of SSI sensitivity without and with hypericum extract did not show and difference and there was no dose-related trend in light sensitivity. Sensitivity to selective UV-A light was increased only after the highest dose from a minimal tanning dose of 10.8 J/ cm2 (mean) after placebo to 8.7 J/cm2 after 3600 mg extract with marginal statistical significance (p = 0.03 by one sided paired t-test). There was no correlation between total hypericin plasma concentration and photosensitivity. In the multiple dose part, 50 volunteers received 600 mg hypericum extract t.i.d. with a daily dose of 5.6 mg of total hypericin. Comparison of UV light sensitivity before dosing with day 15 of treatment showed a slightly increased SSI sensitivity expressed by decrease of the MED from 0.17 to 0.16 J/cm2 (p = 0.005 by Wilcoxon test), and similarly, sensitivity to UV-A light increased (the mean tanning dose decreased from 9.9 to 7.8 J/cm2, p < 0.0001). This increase in cutaneous light sensitivity could be compensated by reducing irradiation time by 21%. Doses used in this study were higher than typical doses in current commercial preparations. In spite of these high doses in the double blind single dose part, frequency of side effects was equal to placebo medication and UV light sensitivity was not or only marginally increased. The study does not, however, exclude phototoxic reactions with doses above 11.25 mg of total hypericin and plasma levels above 100 micrograms/L. Furthermore, phototoxicity may be different after application of pure hypericin, since some constituents in the plant extract may exhibit protective effects.»
Adult, Antidepressive Agents, Cross-Over Studies, Double-Blind Method, Enzyme Inhibitors, Erythema, Female, Humans, Male, Perylene, Photosensitivity Disorders
Modified: 1 month ago
on Jul 7, 2019
1 month ago
on Jul 7, 2019.