Clozapine in Patients with Chronic Schizophrenia: Serum Level, EEG and Memory Performance

Abstract

The atypical antipsychotic clozapine causes EEG alterations, and may lead to memory impairments due to its anticholinergic properties. The relationships between clozapine serum level, quantitative EEG parameters and performance in vigilance and memory tasks were studied in a group of 17 chronically ill schizophrenic patients under maintenance treatment with clozapine at stable dosages. There were negative correlations between clozapine serum levels and the amount of high-frequency EEG activity and positive correlations between high-frequency EEG activity and memory performance. These findings may suggest that clozapine treatment brings about dose-dependent impairments of vigilance and memory, for which a reduction of high-frequency EEG activity is indicative.

Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis

“…There are some reports that CLZ can significantly improve working memory dysfunctions in schizophrenic patients (e.g., Grace et al 1996;Galletly et al 1997Galletly et al , 2005Sharma et al 2003), as opposed to several findings reporting no or even detrimental effects of chronic CLZ treatment on working memory performance in affected individuals (e.g., Hagger et al 1993;Lee et al 1999;Adler et al 2002;McGurk et al 2005). While there has been a long discussion on the involvement of hippocampal dysfunctions in the neuropathology and pathophysiology of schizophrenia (Harrison 1999(Harrison , 2004Weinberger 1999;Antonova et al 2004;Tamminga 2006), the nature and/or severity of hippocampal abnormalities are likely to differ considerably between individual subjects suffering from this disorder.…”

N-Desmethylclozapine, a Major Metabolite of Clozapine, Increases Cortical Acetylcholine and Dopamine Release In Vivo Via Stimulation of M1 Muscarinic Receptors

“…The ability of APDs to improve some or all aspects of the cognitive deficit in schizophrenia (Meltzer and McGurk, 1999;Woodward et al, 2005) has been attributed, in part, to their ability to preferentially increase the release of dopamine (DA) (Imperato and Angelucci, 1989;Moghaddam and Bunney, 1990;Kuroki et al, 1999) and ACh in the cortex and HIP (Ichikawa et al, 2002a, b;Shirazi-Southall et al, 2002;Chung et al, 2004), while the anticholinergic activity of clozapine, olanzapine, thioridazine, and mesoridazine has been suggested to interfere with memory (Eitan et al, 1992;Adler et al, 2002;McGurk et al, 2004). The increased DA release induced by the atypical APDs may be due, in part, to blockade of serotonin 5-HT 2A and D 2 receptors, and direct or indirect stimulation of 5-HT 1A receptors (Ichikawa et al, 2001).…”

Clozapine-Induced QEEG Changes Correlate with Clinical Response in Schizophrenic Patients: a Prospective, Longitudinal Study

“…The mechanism of CLO-induced theta increase is not completely understood, but the potent anticholinergic effect of CLO has been proposed as one plausible explanation [1], the parallel effect of several modulatory systems affected by CLO also being possible.…”