A transcranial magnetic stimulation study of the effects of olanzapine and risperidone on motor cortical excitability in patients with schizophrenia

Rationale: There has been a progressive increase in interest in the functioning of the main inhibitory and excitatory neurotransmitters in the pathophysiology of schizophrenia. Limited information is available as to how these neurotransmitters are affected by commonly prescribed antipsychotic agents. Objectives: We investigated whether the atypical antipsychotics olanzapine and risperidone differ in their effects on inhibitory and excitatory cortical markers measured with transcranial magnetic stimulation. Methods: Electromyographic recordings from the abductor pollicis brevis muscle were made during focal transcranial magnetic stimulation to the contralateral motor cortex and during bilateral cortical stimulation. Twenty patients on each drug, and 22 controls were studied with measures of the resting motor threshold, motor evoked potential size, post-excitatory silent period duration, cortical inhibition and facilitation to paired-pulse transcranial magnetic stimulation and transcallosal inhibition. Results: The patient groups differed from the controls in the silent period and transcallosal inhibition measures, both of which assess cortical inhibitory activity. The two medication groups differed in the magnitude of the resting motor threshold and several measures of transcallosal inhibition that reflect the spread of inhibitory activity between hemispheres. Conclusions: These findings suggest that olanzapine and risperidone differ subtly in their effects on cortical inhibitory mechanisms. Further evaluation is required to establish whether these differences may reflect or underlie differences seen between these medications in their clinical profiles, including their effects on cognitive symptoms of schizophrenia.