The effects of St John's wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men.
OBJECTIVE
To compare the effects of multiple dosing with St John's wort (Hypericum perforatum) extract and amitriptyline on heart rate variability, cognitive function and quantitative EEG (qEEG) with placebo in healthy humans.


METHODS
A randomized, double-blind, cross over study of 12 healthy male volunteers. Subjects orally received capsules with 255-285 mg St John's wort extract (900 micro g hypericin content), 25 mg amitriptyline and placebo three times daily for periods of 14 days each with at least 14 days between. The doses of amitriptyline and St John's wort extract are comparable with respect to their antidepressant activity. Compliance was confirmed by coadministration of 10 mg of riboflavin with each capsule and detection of urinary vitamin B2 on treatment day 11 with high performance liquid chromatography. Measurements of heart rate variability, psychometric tests and qEEG were performed before start of medication and repeatedly on the last treatment day.


RESULTS
St John's wort extract did not affect heart rate variability (HRV) whereas amitripytline significantly decreased it: the difference in the percentage number of adjacent RR intervals> 50 ms (pNN50) was 8.6 (-2.6, 19.9; mean; 95% confidence interval) between St John's wort extract and placebo and -17.6 (-24.7, -10.4) between amitriptyline and placebo. Neither St John's wort extract nor amitriptyline had an influence on cognitive performance such as choice reaction, psychomotor coordination, short-term memory and responsiveness to distractive stimuli. Amitriptyline but not St John's wort extract decreased self rated activity (P < 0.05). Both drugs caused significant qEEG changes. St John's wort extract increased theta power density. Amitriptyline increased theta as well as fast alpha power density.


CONCLUSIONS
Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.
Siepmann
M
M
Institute of Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany. Martin.Siepmann@mailbox.tu-dresden.de
Krause
S
S
Joraschky
P
P
Mück-Weymann
M
M
Kirch
W
W
D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D020902:Hypericum; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011594:Psychometrics; D011930:Reaction Time
D000929:Antidepressive Agents, Tricyclic; D010936:Plant Extracts; D000639:Amitriptyline