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Haloperidol and Risperidone May Produce Opposite Effects on Human Corticospinal System in Schizophrenic Patients

Haloperidol and risperidone -- two drugs used for treatment of schizophrenic -- might have a clear difference in pharmacologically-induced changes in corticospinal excitability.

In a previous electrophysiological investigation of schizophrenia using transcranial magnetic stimulation, Basant K. Puri, MA, MB, BChir, MRCPsych, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom, and colleagues observed altered corticospinal inhibition in medicated patients compared with drug-naïve patients.

Using similar techniques, these researchers performed a study of the time-course of drug action in two antipsychotic drug-naïve schizophrenic patients, one patient treated with the typical antidopaminergic antipsychotic haloperidol and the other with the atypical antipsychotic risperidone.

Both subjects were men in their early twenties with first-episode schizophrenia. Immediately after neurophysiological and clinical assessments, one patient began haloperidol treatment at a dose of 6 mg/day, which was increased to 16 mg/day 6 days later for the study duration, and the second patient began risperidone treatment at 2 mg/day, incrementally increased to 6 mg/day for the study duration.

After initial assessment, the patients were evaluated at intervals of 2 to 11 days up to 6 weeks.

Symptoms were rated using the Schedule for the Assessment of Positive Symptoms (SAPS) and the Schedule for the Assessment of Negative Symptoms (SANS). Electrophysiological measurements were obtained by electromyograms and electromagnetic stimulation of the cerebral motor cortex.

Results showed that use of haloperidol was associated with increased overall corticospinal excitability, as evidenced by an increase in motor evoked potential area 4 to 5 weeks after treatment initiation, while risperidone decreased overall corticospinal excitability, as evidenced by a decrease in motor evoked potential area 3 to 4 weeks post-treatment.

Interestingly, the SAPS score associated with haloperidol improved within a few days of the increase in corticospinal excitability. Alternatively, the SAPS score was reduced 2 to 3 weeks in advance of the decrease in corticospinal excitability associated with risperidone.

It is likely that the opposite neurophysiological effects are related to the relative dopaminergic and serotonergic actions of the two classes of drug, the investigators write.

"This electrophysiological approach to the investigation of pharmacological actions of psychotropic agents in the human brain may be informative in the exploration and differentiation between putative antipsychotics," they conclude.
Int J Clin Pract 2003 Nov;57:9:831-3. "Excitability of the motor cortex in schizophrenia following typical and atypical antipsychotics: two serial case reports"

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