Multilead quantitative electroencephalogram profile and cognitive evoked potentials (P300) in healthy subjects after a single dose of olanzapine

Rationale: Olanzapine is an atypical antipsychotic drug with a more favoura ble safety profile than typical antipsychotics with a hitherto unknown topo graphic quantitative electroencephalogram (QEEG) profile. Objectives: We in vestigated electrical brain activity (QEEG and cognitive event related pote ntials, ERPs) in healthy subjects who received olanzapine. Methods: Vigilan ce-controlled, 19-channel EEG and ERP in an auditory odd-ball paradigm were recorded before and 3 h, 6 h and 9 h after administration of either a sing le dose of placebo or olanzapine (2.5 mg and 5 mg) in ten healthy subjects. QEEG was analysed by spectral analysis and evaluated in nine frequency ban ds. For the P300 component in the odd-ball ERP, the amplitude and latency w as analysed. Statistical effects were tested using a repeated-measurement a nalysis of variance. Results: For the interaction between time and treatmen t, significant effects were observed for theta, alpha-2, beta-2 and beta-4 frequency bands. The amplitude of the activity in the theta band increased most significantly 6 li after the 5-mg administration of olanzapine. A pron ounced decrease of the alpha-2 activity especially 9 h after 5 mg olanzapin e administration could be observed. In most beta frequency bands, and most significantly in the beta-4 band, a dose-dependent decrease of the activity beginning 6 h after drug administration was demonstrated. Topographic effe cts could be observed for the beta-2 band (occipital decrease) and a tenden cy for the alpha-2 band (frontal increase and occipital decrease), both ind icating a frontal shift of brain electrical activity. There were no signifi cant changes in P300 amplitude or latency after drug administration. Conclu sion: QEEG alterations after olanzapine administration were similar to EEG effects gained by other atypical antipsychotic drugs, such as clozapine. Th e increase of theta activity is comparable to the frequency distribution ob served for thymoleptics or antipsychotics for which treatment-emergent somn olence is commonly observed, whereas the decrease of beta activity observed after olanzapine administration is not characteristic for these drugs. The re were no clear signs for an increased cerebral excitability after a singl e-dose administration of 2.5 mg and 5 mg olanzapine in healthy controls.