Study 21
Effects of hypericum extract on the sleep EEG in older volunteers
Au: Schulz and M. Jobert
So: J Geriatr Psych in. try Neurol 1994; 7(suppl 1): PP 39-43
Introduction
Sleep is an actively controlled resting state associated with characteristic changes in central nervous activity. The various stages of sleep can be distinguished and the cyclic course of sleep demonstrated with the help of EEGs and other electrophysiologic parameters (electromyogram, EMG; electrooculogram, EOG). The EEG, EMG, and EOG biosignals can be evaluated either visually or by automated means. It is also possible to differentiate between the non-REM (NREM) stages 1, 2, 3, and 4 of sleep and REM sleep. Due to the marked delta activity in the EEG (slow, high-amplitude waves in the frequency range below 4 Hz) recorded during the NREM stages 3 and 4, these stages are also known as slow-wave sleep.
Depressive illnesses are accompanied by characteristic changes in sleep. Sleep is fitful, and early waking is frequent. Slow-wave sleep can be reduced and the time between sleep onset and the appearance of the first REM sleep in the night (REM latency) is shortened.
An increased activity of cholinergic systems with a simultaneous weakening of aminergic transmitter systems has been postulated as the neurobiologic basis of these changes in sleep structure.
Antidepressants intervene in this process and lead to typical changes in sleep profile. With tricyclic antidepressants, this intervention includes a prolongation of REM latency and a reduction in REM sleep, which can be associated with a marked flattening of the ultradian rhythm (physiological activities that occur more than once every 24 hours).
Description
Twelve older female volunteers with a mean age of 60 years went through two 4-week treatment phases (placebo and active treatment) separated by a washout period of 14 days. Active treatment was given with the hypericum extract LI 160 (Jarsin) in a daily dose of 3 x 0.9 mg hypericin). The 12 subjects were divided into two groups: Group I received LI 160 in the first 4 weeks and a placebo in the second phase, and group II began with the 4 weeks of placebo and was transferred to LI 160 in the second phase.
Each subject spent a total of 4 nights (study days 2, 30, 44, and 72) in the sleep laboratory, when the sleep polygraph was recorded. Each of these nights was preceded by an adaptation night (study days 1, 29, 43, and 71).
Conclusion
The aim of this double-blind study was to investigate the effects of 4 weeks of treatment with hypericum on sleep and well-being. The purpose was to find out whether hypericum's action on sleep is comparable to that of the tricyclic antidepressants and nonselective MAO inhibitors, which cause a prolongation in REM latency and a suppression of REM sleep.
The results show that hypericum has a different profile of action: contrary to the working hypothesis, under active treatment there was actually a slight reduction (on average 10 minutes) in REM sleep latency, whereas under the placebo, the median REM sleep latency remained virtually unchanged. It cannot, however, be ruled out that changes in REM sleep occurred at the start of treatment with hypericum that were not detected when they were measured 4 weeks later.
The proportion of REM sleep in the total sleep period was within the normal range at 20% and was not altered by treatment with hypericum. In the investigated group of older, healthy volunteers, several weeks of treatment with hypericum thus had no effect on the time of appearance or amount of REM sleep.
The observation that the total amount of sleep fell slightly during active treatment and the waking period increased indicates that hypericum does not have any sedative potential, but rather a moderate activating effect on wakefulness. This effect of hypericum can depend, however, both on the dose and the time of ingestion.
Notably, there was an increase in slow-wave sleep in the deep stages 3 and 4 under treatment with hypericum. The baseline value of slow-wave sleep in the subjects was low and amounted on average to less than 5% of the total. This small proportion corresponds to the known reduction in deep sleep with increasing age.
The increase in sleep stages 3 and 4 in the visual evaluation of the sleep EEG corresponded with the increase in slow-wave activity in the automated analysis, which enabled the output in the delta-frequency range to be quantified. This result might be associated with the clinically observed antidepressant effect of LI 160, since several authors assume that a deficit in slow-wave sleep is a significant neurobiologic indicator in affective disorders. Kupfer et al. also reported that the prognosis in patients with depression who had a high proportion of slow-wave activity in the sleep EEG (delta sleep ratio") was considerably more favorable than in those patients with low values. According to the results of the present study, the neurophysiologic activity of LI 160 is displayed more in terms of slow-wave EEG activity than in parameters of REM sleep.
Copyright © 1996 by Harold H. Bloomfield, M.D. and Peter McWilliams
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