Neuroleptic-induced akathisia is a distressing side effect of antipsychotics, and it is unmanageable in some cases. The authors report three cases of schizophrenia whose neuroleptic-induced akathisia did not respond to representative anti-akathisia drugs such as beta-adrenergic antagonists, anticholinergic agents, benzodiazepines and antihistaminergics, and they showed a marked improvement of it without worsening of psychotic symptoms dining a combination treatment with carbamazepine and perospirone, a serotonin-dopamine antagonist developed in Japan. As the mechanism of current observation, we assumed that carbamazepine affected the pharmacokinetics of perospirone, and change in the proportion of perospirone and its major active metabolite (ID-15036). Further investigations including the monitoring pharmacokinetics of perospirone and ID-15036 under concomitant use of carbamazepine should be carried out to explain the mechanism of the current experience. (C) 2004 Elsevier Inc. All rights reserved.