Abstract
Rationale
Quetiapine is increasingly used for the treatment of patients with psychosis and bipolar disorder. However, the neurobiological mechanisms, which may account for the favourable risk/benefit profile of this drug, are not entirely understood.
Objectives
Transcranial magnetic stimulation was used to investigate the effects of acute and repeated administration of quetiapine on cortical excitability in healthy volunteers.
Materials and methods
Within a double-blind, placebo-controlled, randomized cross-over design motor threshold, intracortical inhibition, intracortical facilitation and cortical silent period were studied in 15 healthy volunteers before and after a single dose of placebo and 100 mg quetiapine. Additional measurements were performed after 5 days of daily intake of 100 mg quetiapine.
Results
We observed a significant prolongation of the cortical silent period after a single dose of quetiapine, whereas the placebo had no effects. After repeated administration, there was a trend towards CSP prolongation, which did not reach significance. However, plasma concentrations at this time point were relatively low, as measurements were performed 15 h after the last drug intake. Other parameters of cortical excitability remained unaffected.
Conclusions
By lengthening CSP without affecting MT, ICI and ICF, quetiapine demonstrates a unique neurophysiological profile which differs distinctively from brain excitability profiles of typical antipsychotics such as haloperidol. Provided that the CSP prolongation reflects the antipsychotic potential of quetiapine, TMS may be developed as a tool to monitor neurobiological effects of quetiapine treatment in schizophrenic patients and to explore the efficacy of other antipsychotic drugs with a similar mode of action.
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Acknowledgements
The authors wish to thank Sandra Pfluegl and Helene Niebling for technical assistance and Astra Zeneca, Germany, for funding of the study.
Conflict of interest statement
The study has been funded by a grant from Astra Zeneca. None of the authors has any further conflict of interest with respect to this study. The company Astra Zeneca did not have any influence on the conduct of the study, the collection, management, analysis, and interpretation of data, the writing of the manuscript or the decision to submit the manuscript for publication.
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Berthold Langguth, Peter Eichhammer contributed equally to the manuscript.
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Langguth, B., Eichhammer, P., Spranz, C. et al. Modulation of human motor cortex excitability by quetiapine. Psychopharmacology 196, 623–629 (2008). https://doi.org/10.1007/s00213-007-1000-z
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DOI: https://doi.org/10.1007/s00213-007-1000-z