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The effect of psychotropic drugs on cortical excitability and plasticity measured with transcranial magnetic stimulation: Implications for psychiatric treatment

Abstract

Objective

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for neuropsychiatric disorders. Patients in rTMS treatment typically receive concomitant psychotropic medications, which affect neuronal excitability and plasticity and may interact to affect rTMS treatment outcomes. A greater understanding of these drug effects may have considerable implications for optimizing multi-modal treatment of psychiatric patients, and elucidating the mechanism(s) of action (MOA) of rTMS.

Method

We summarized the empirical literature that tests how psychotropic drugs affect cortical excitability and plasticity, using varied experimental TMS paradigms.

Results

Glutamate antagonists robustly attenuate plasticity, largely without changes in excitability per se; antiepileptic drugs show the opposite pattern of effects, while calcium channel blockers attenuate plasticity. Benzodiazepines have moderate and variable effects on plasticity, and negligible effects on excitability. Antidepressants with potent 5HT transporter inhibition reduce both excitability and alter plasticity, while antidepressants with other MOAs generally lack either effect. Catecholaminergic drugs, cholinergic agents and lithium have minimal effects on excitability but exhibit robust and complex, non-linear effects in TMS plasticity paradigms.

Limitations

These effects remain largely untested in sustained treatment protocols, nor in clinical populations. In addition, how these medications impact clinical response to rTMS remains largely unknown.

Conclusions

Psychotropic medications exert robust and varied effects on cortical excitability and plasticity. We encourage the field to more directly and fully investigate clinical pharmaco-TMS studies to improve outcomes.

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