Clozapine potentiation of GABA mediated cortical inhibition in treatment resistant schizophrenia

Tyler S. Kaster, Danilo Rocha de Jesus, Natasha Radhu, Faranak Farzan, Daniel M Blumberger, Tarek K Rajji, Paul B. Fitzgerald, Zafiris Jeff Daskalakis

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)


Background: Cortical inhibition (CI) deficits have been demonstrated in schizophrenia using transcranial magnetic stimulation (TMS). These CI deficits may be related to decreased GABA activity which may be involved in schizophrenia pathophysiology. Previous cross-sectional studies have also demonstrated greater CI in patients treated with clozapine than other typical/atypical antipsychotics. However, it is not clear if these differences in CI are a result of treatment-resistant illness which necessitates clozapine or are related to clozapine treatment. Methods: TMS measures of CI (i.e., cortical silent period (CSP) and short-interval cortical inhibition (SICI)) were measured over the motor cortex in 16 patients with schizophrenia before starting clozapine, then 6. weeks and 6. months after starting clozapine. Results: CSP was significantly longer after 6. weeks of treatment with clozapine (p = 0.014). From 6. weeks to 6. months, there was no significant difference in CSP (p > 0.05). Short-interval cortical inhibition (SICI) was not significantly different at any time after treatment with clozapine (p > 0.05). Conclusions: This prospective-longitudinal study demonstrates that treatment with clozapine is associated with an increase in GABAB mediated inhibitory neurotransmission. Potentiation of GABAB may be a novel neurotransmitter mechanism that is involved in the pathophysiology and treatment of schizophrenia.

Original languageEnglish
Pages (from-to)157-162
Number of pages6
JournalSchizophrenia Research
Issue number2-3
Publication statusPublished - 1 Jul 2015


  • Clozapine
  • Cortical inhibition
  • GABA
  • Schizophrenia
  • Transcranial magnetic stimulation

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