Although several problems in the clinical practice of Japanese psychiatry have been reported, antipsychotic polypharmacy comprising three to four drugs is more common in Japan than in Western countries, indicating that the situation has not improved. The resting heart rate (RHR) among the general population was found to be related to the relative risk of overall mortality and sudden cardiac death. Antipsychotics are known to have RHR elevating effects via alpha (1A) adrenergic receptor blockade or muscarinic receptor blockade, but the detailed mechanisms are unclear. In this study, we examined the effects of antipsychotic polypharmacy on RHR in approximately 8,000 Japanese patients with schizophrenia.
 Of the examined patients, 56.3% were treated using antipsychotic polypharmacy and 21.2% were treated using more than three antipsychotics. The RHR increased with the number of antipsychotics used, and the mean RHR was nearly 80 beats per minute in the groups using more than three antipsychotics in combination, being approximately 10 beats per minute higher than that in the untreated group. Therefore, antipsychotic polypharmacy may be related to the high mortality risk of schizophrenia.
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