Following recent dissemination of various guidelines and algorithms and spread of second-generation antipsychotics, the view laying emphasis on “single antipsychotic regimen” has been well known as far as drug therapy for schizophrenia is concerned. In practice, monotherapy using one of the second-generation antipsychotics is gradually spreading as a means of treating the acute stage of schizophrenia. However, according to studies on the frequency of using polypharmacy in Japan,the percentage of cases treated with a monotherapy still remains lower than that in foreign countries,although there is a tendency for rise in the percentage. One possible reason for the low percentage of cases treated with a monotherapy in Japan relative to that in foreign countries is the persisting practice of applying polypharmacy to the hospitalized patients,particularly to the long-term hospitalized patients and chronically sick patients in Japan. Some of these patients receive high-dose treatment with multiple drugs, including various antipsychotics and anti-Parkinsonian drugs, and it is not easy for these patients to be managed with monotherapy even though the view“monotherapy is appropriate”has been spreading. Furthermore, there is poor evidence supporting switching of high-dose polypharmacy to monotherapy,and the methodology for such switching has not yet been established. In practice,it is often difficult to apply monotherapy to long -term hospitalized patients or chronically sick patients in the way similar to that applied to acutely sick patients or patients with first-onset schizophrenia. This paper will discuss the feasibility of switching to monotherapy in long-term hospitalized patients and chronically sick patients on the basis of our experience in the past and will present our experience with switching polypharmacy to monotherapy and our way of augmentation therapy for monotherapy, on the basis of the concept “optimization of prescriptions”rather than “simply reducing the number of drugs prescribed to one.”