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Clinical Improvement with Dose Reduction in Patients with Chronic Schizophrenia on High-Dose Antipsychotic Polypharmacy

Dose reduction is successful in most cases of high-dose antipsychotic polypharmacy in patients with chronic schizophrenia, according to a recent Japanese study.

Early studies indicated benefits of high-dose antipsychotic therapy. However, more recent studies in patients with schizophrenia have suggested that high-dose therapy is not effective and should not be used in as routine practice. Unfortunately, overdosing and polypharmacy still occur in the real-world clinical setting.

Takefumi Suzuki and colleagues at the Keio University, Tokyo, Japan, evaluated the effects of dose reduction in a daily, clinical setting in patients with chronic schizophrenia who had been treated with high-doses of antipsychotics.

The study included 41 patients (27 men, average age 46) with chronic schizophrenia, 81% of whom had been treated with an antipsychotic high-dose polypharmacy regimen (equivalent of 1000 mg/day chlorpromazine).

Dose reduction was initiated with the least potent antipsychotic in the patient's regimen and was carried out in a conservative, gradual manner. Patients were followed for 6 months after termination of dose reduction and assessed by the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF) criteria.

Successful dose reduction was attained in 88% (36) of patients. Improvement was seen in 23 patients after dose reduction and 13 patients showed no change. However, symptoms worsened in 5 patients (12%). Significant overall improvements were seen in both the GAF and the Severity of Illness scores.

The initial dose could be effectively reduced by 59.1%, as the medication dose dropped significantly from 1984 mg/day to 812 mg/day. While the average number of medications used was 3.6 at the start of the study, the average number decreased to 2.2 by a median of 3 months (P < .0001). Moreover, 26.8% of patients were taking antipsychotic monotherapy and 49% were taking approximately 50mg of low-potency dosing.

Unfortunately, no significant predictors of success of dose reduction were identified in this study.

The authors conclude that "dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past."

They also highlight the important finding regarding the "possibility for clinical improvement after reducing the dose of antipsychotic medications."

Int Clin Psychopharmacol 2003 Nov;18:6:323-9. "Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: an open study of dose reduction for chronic schizophrenia"

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