Clozapine Prolongs Cortical Silent Period in Patients with Treatment-Resistant Schizophrenia

Atsuhiro Miyazawa; Nobuhisa Kanahara; Yusuke Nakata; Satoshi Kodama; Hiroshi Kimura; Atsushi Kimura; Yasunori Oda; Hiroyuki Watanabe; Masaomi Iyo

Clozapine Prolongs Cortical Silent Period in Patients with Treatment-Resistant Schizophrenia

Psychopharmacol Bull. 2021 Mar 16;51(2):20-30.

Authors

Atsuhiro Miyazawa¹, Nobuhisa Kanahara¹, Yusuke Nakata¹, Satoshi Kodama¹, Hiroshi Kimura¹, Atsushi Kimura¹, Yasunori Oda¹, Hiroyuki Watanabe¹, Masaomi Iyo¹

Affiliation

¹ Miyazawa, MD, Nakata, MD, PhD, Atsushi Kimura, MD, PhD, Oda, MD, PhD, Iyo, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. Kanahara, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan, Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan. Kodama, MD, PhD, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Hiroshi Kimura, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan, Department of Psychiatry, International University of Health and Welfare, Chiba, Japan. Watanabe, MD, PhD, Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan, Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan.

PMID: 34092820
PMCID: PMC8146563

Abstract

Objectives: Although clozapine exhibited high efficacy for treating the symptoms of patients with treatment-resistant schizophrenia (TRS), its precise action mechanisms have not been fully understood. Recently, accumulating evidence has suggested the presence of abnormalities in the gamma-aminobutyric acid (GABA) systems in patients with schizophrenia, and the potential effects of clozapine on GABA receptors have gained a great deal of attention.

Experimental designs: In the present study, the cortical silent period (CSP), an electrophysiological parameter of GABA function via GABA_B receptors, was measured using with the transcranial magnetic stimulation in patients with schizophrenia and healthy control subjects. Then the CSP of patients treated with clozapine (N = 12) was compared with that of patients treated with other antipsychotics (N = 25) and with that of healthy controls (N = 27).

Principal observations: The CSP of the patients treated with clozapine was significantly longer compared to those of the other two groups. The CSP of patients treated with other antipsychotics was similar to that of healthy subjects. There was a positive correlation between CSP and global assessment of function (GAF) in patients with TRS.

Conclusions: The present study indicated that CSP was prolonged in patients receiving clozapine, and suggested that clozapine enhances the transmission signal via GABAB receptors.

Keywords: GABA; antipsychotic; cortical inhibition; transcranial magnetic stimulation; treatment-resistant.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antipsychotic Agents* / therapeutic use
Clozapine* / therapeutic use
Humans
Schizophrenia, Treatment-Resistant / drug therapy*
Transcranial Magnetic Stimulation

Substances

Antipsychotic Agents
Clozapine