Evaluation of the Individual Safe Correction of Antipsychotic Agent Polypharmacy in Japanese Patients with Chronic Schizophrenia: Validation of Safe Corrections for Antipsychotic Polypharmacy and the High-Dose Method

Abstract

Background:Polypharmacy for schizophrenia treatment is not justified by the available clinical evidence. We evaluated a treatment reduction approach that reduces the dose and number of antipsychotic medications simultaneously prescribed to patients.Methods:In a randomized open study of the Safe Correction of Antipsychotic Polypharmacy and High-Dose Prescriptions program funded by the Japanese Ministry of Health, Labour, and Welfare, we evaluated a drug reduction method consisting of a dose reduction intervention performed on 163 patients with schizophrenia for twelve or 24 weeks. One antipsychotic medication was removed each week from each patient’s treatment regimen by reducing the dose by 0 to 50 chlorpromazine equivalents. Data on health-related indices of quality of life, clinical symptoms, and risk of side effects were analyzed using a two-way repeated-measures mixed linear model.Results:Despite a 23% reduction in antipsychotic dose, no differences in outcomes were observed between the dose reduction and observation groups (effect size = 0.001 – 0.085, P = .24–.97), despite high statistical power (1-β = 0.48–0.97). The findings are limited by the nonuniformity of the participants’ treatment history, duration, and dose reduction amount. Dose reduction protocol patients exhibited no difference in psychotic symptoms or adverse events compared with the observation group.Conclusions:Importantly, the low dropout rate in our study (6.9% of participants withdrew because of patient factors and 23.8% for all secondary reasons) indicates that our “slowly” method is well tolerated. We hope that this approach will result in therapeutic improvements.

Polypharmacy and psychotropic drug loading in patients with schizophrenia in Asian countries: Fourth survey of Research on Asian Prescription Patterns on antipsychotics

“…In Japan, the use of high doses of antipsychotics and polypharmacy has been conventionally prevalent . To reduce the high rate of polypharmacy, psychotropic dose equivalence has been suggested for dose standardization; in addition, the public insurance reimbursement system, drug reduction program, and pharmacist intervention policies have been revised to improve and prevent psychotropic polypharmacy . Our results indicated that the rate of polypharmacy has reduced in recent years in Japan; nevertheless, among the Asian countries included here, Japan still has the highest average number of antipsychotic use (1.8 ± 0.9) and antipsychotic loading (2.29 ± 1.79).…”

Effectiveness in Switching from Antipsychotic Polypharmacy to Monotherapy in Patients with Schizophrenia: A Case Series

“…According to the SCAP protocol [9], the dosage of one antipsychotic agent was reduced every week for the subjects in the dose-reduction group. The choice of agent to be reduced in dose was left to the discretion of the physician.…”

“…Monotherapy is recommended due to the following dis-advantages of high-dose antipsychotic polypharmacy [7]: 1) difficulty in evaluating which drug is effective or ineffective, 2) difficulty in deciding the optimal dosage, 3) difficulty in identifying the causes of adverse reactions, 4) complex regimens that increases the frequency of administration mistakes, thus enhancing the stress of the patient's family or nursing staff, 5) drug interactions, and 6) reduced compliance. To overcome these challenges, a method for safely correcting high-dose antipsychotic polypharmacy (SCAP method) has been proposed [8,9]. In the SCAP method, it is recommended that when the titer of an antipsychotic agent is high, the dose be reduced by 0 to 50 mg/week as a chlorpromazine (CP)-converted value, and that when the titer is low, the dose be reduced by 0 to 25 mg/week as a CP-converted value [8,9].…”

“…To overcome these challenges, a method for safely correcting high-dose antipsychotic polypharmacy (SCAP method) has been proposed [8,9]. In the SCAP method, it is recommended that when the titer of an antipsychotic agent is high, the dose be reduced by 0 to 50 mg/week as a chlorpromazine (CP)-converted value, and that when the titer is low, the dose be reduced by 0 to 25 mg/week as a CP-converted value [8,9]. These dose-reduction rates have been designed to avoid the withdrawal symptoms mediated by dopaminergic D2, cholinergic or other receptors.…”

“…In the present study, we reduced the number and doses of antipsychotic agents (dose-reduction) in patients with schizophrenia using the SCAP method [8,9] and also reduced the dosages of antiparkinson and benzodiazepine drugs. In addition, we evaluated psychiatric symptoms and adverse reactions of patients in whom the number and doses of antipsychotic agents were reduced and con- ducted a survey regarding their satisfaction.…”