Electroencephalogram slowing, sleepiness and treatment response in patients with schizophrenia during olanzapine treatment

Abstract

Electroencephalogram (EEG) slowing is associated with clozapine side effects, e.g., sedation, and may predict treatment response during clozapine treatment. As olanzapine and clozapine share many pharmacological properties, we investigated whether EEG slowing during olanzapine treatment was related to therapy outcome and sleepiness in patients with schizophrenia. Participants were age- and gender-matched schizophrenic patients treated with olanzapine (n 54), receiving no pharmacological treatment (n 54), or cotreated with olanzapine and some other psychotropic drug (n 38). Their EEG recordings were assessed visually by the same rater blind to clinical data. The EEG scores were categorized using standardized forms. Patients with a poor treatment response did not differ significantly from those with a good response to treatment either in EEG patterns or in frequency of sleepiness. Olanzapine treatment was associated with increased rates of slow (70.4% vs. 22.3%) and sharp waves (22.2% vs. 7.4%), as well as of paroxysmal slow wave discharges (14.8% vs. 1.9%), but did not induce spike- or sharp-slow-wave complexes. Cotreatment with another antipsychotic further increased EEG abnormalities, whereas benzodiazepine administration diminished the olanzapine-induced EEG changes. The results show that olanzapine inducing both slow and sharp waves, as well as paroxysmal discharges, has a strong impact on EEG. However, as no spike- or sharp-slow-wave complexes were observed, the risk of epileptic seizure during olanzapine treatment can be regarded as low, as long as olanzapine is not combined with some other antipsychotic.

State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 – Relation to antipsychotic-like drug effects

“…However, VU0467154 did not alter the power spectra when administered during the dark period while rodents are most alert, consistent with a lack of potential sedating or hyper-arousing effects of the M 4 PAM mechanism. In contrast, clozapine increased low, and decreased high power, consistent with the sedative effects of APDs in medicated patients with schizophrenia (Boutros et al, 2008; 2014; Goder et al, 2006; Keshavan et al, 1995a; Wichniak et al, 2006). Clozapine and xanomeline administration produced similar effects, regardless of dosing during the light or dark period.…”

“…However, the effects of clozapine and other APDs on sleep do not substantially improve cognition (Barch and Ceaser, 2012; Nuechterlein et al, 2004), perhaps due to residual sedative effects during wake. Daytime drowsiness or decreased arousal is common following APD administration in healthy humans, schizophrenia patients, and in healthy rats (Ahnaou et al, 2003; Czobor and Volavka, 1993; Dimpfel, 2007; Hughes et al, 1999; Roubicek and Major, 1977; Wichniak et al, 2006; Yoshimura et al, 2007). In the present studies, VU0467154 altered sleep in a manner similar to clozapine, suggesting potential APD-like activity on sleep architecture, but lacked the sedative profile of clozapine during waking periods.…”

“…In addition to polysomnography, quantitative electroencephalography (qEEG) approaches have correlated aberrant brain oscillation patterns with specific symptoms in unmedicated schizophrenia patients and adverse side effect profiles of antipsychotic drugs (APDs) in medicated patients (Boutros et al, 2008; 2014; Goder et al, 2006; Keshavan et al, 1995a; Wichniak et al, 2006). For example, elevated power in the high frequency gamma band (e.g., >30 Hz in humans) is associated with positive symptoms, whereas lower gamma power at rest and reduced elevations in gamma power during cognitive testing is linked to cognitive impairments (Baldeweg et al, 1998; Chen et al, 2014; Lee et al, 2003; Uhlhaas and Singer, 2014).…”

EEG alterations during treatment with olanzapine

“…Wichniak et al [20] reported that the risk of epileptic seizures under olanzapine treatment can be regarded as low as long as olanzapine is administered as a monotherapy. In addition to this, an excess increase in the dosage of olanzapine should be regarded with caution.…”

Crises epilépticas e uso de olanzapina: relato de dois casos

“…(5,9,10) Quanto às anormalidades do EEG, em nossos casos não houve lentificação da atividade elétrica cerebral de base que é o achado mais freqüente associado à olanzapina. (4,9,10,11) Em relação à AE ao EEG, com o uso de olanzapina, há poucos relatos na literatura e, estes por vezes, são contraditórios.…”