A pharmaco-EEG study on antipsychotic drugs in healthy volunteers.
BACKGROUND
Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle).


OBJECTIVE
We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle.


METHODS
Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands.


RESULTS
Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1.


CONCLUSIONS
The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics.
Yoshimura
Masafumi
M
Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bern, Switzerland. yoshimum@takii.kmu.ac.jp
Koenig
Thomas
T
Irisawa
Satoshi
S
Isotani
Toshiaki
T
Yamada
Keizo
K
Kikuchi
Mitsuru
M
Okugawa
Gaku
G
Yagyu
Takami
T
Kinoshita
Toshihiko
T
Strik
Werner
W
Dierks
Thomas
T
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D018592:Cross-Over Studies; D003987:Dibenzothiazepines / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D005583:Fourier Analysis; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D012016:Reference Values; D018967:Risperidone / Q000494:pharmacology; D016037:Single-Blind Method; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D007211:Indoles; D054833:Isoindoles; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D006220:Haloperidol; D018967:Risperidone; C065533:perospirone; D000077152:Olanzapine; D002746:Chlorpromazine