Abstract

BackgroundData are limited on the benefits and risks of dose reduction in managing side effects associated with antipsychotic treatment. As an example, antipsychotic dose reduction has been recommended in the management of tardive dyskinesia (TD), yet the benefits of lowering doses are not well studied. However, stable maintenance treatment is essential to prevent deterioration and relapse in schizophrenia.MethodsA retrospective cohort study was conducted to analyze the healthcare burden of antipsychotic dose reduction in patients with schizophrenia. Medical claims from six US states spanning a six-year period were analyzed for ≥10% or ≥ 30% antipsychotic dose reductions compared with those from patients receiving a stable dose. Outcomes measured were inpatient admissions and emergency room (ER) visits for schizophrenia, all psychiatric disorders, and all causes, and TD claims.ResultsA total of 19,556 patients were identified with ≥10% dose reduction and 15,239 patients with ≥30% dose reduction. Following a ≥ 10% dose reduction, the risk of an all-cause inpatient admission increased (hazard ratio [HR] 1.17; 95% confidence interval [CI] 1.11, 1.23; P < 0.001), and the risk of an all-cause ER visit increased (HR 1.09; 95% CI 1.05, 1.14; P < 0.001) compared with controls. Patients with a ≥ 10% dose reduction had an increased risk of admission or ER visit for schizophrenia (HR 1.27; 95% CI 1.19, 1.36; P < 0.001) and for all psychiatric disorders (HR 1.16; 95% CI 1.10, 1.23; P < 0.001) compared with controls. A dose reduction of ≥30% also led to an increased risk of admission for all causes (HR 1.23; 95% CI 1.17, 1.31; P < 0.001), and for admission or ER visit for schizophrenia (HR 1.31; 95% CI 1.21, 1.41; P < 0.001) or for all psychiatric disorders (HR 1.21; 95% CI 1.14, 1.29; P < 0.001) compared with controls. Dose reductions had no significant effect on claims for TD.ConclusionPatients with antipsychotic dose reductions showed significant increases in both all-cause and mental health–related hospitalizations, suggesting that antipsychotic dose reductions may lead to increased overall healthcare burden in some schizophrenia patients. This highlights the need for alternative strategies for the management of side effects, including TD, in schizophrenia patients that allow for maintaining effective antipsychotic treatment.

Highlights

  • Data are limited on the benefits and risks of dose reduction in managing side effects associated with antipsychotic treatment

  • Study objective and data sources A large retrospective cohort study using electronic medical records was conducted to compare the risk of all-cause and mental health–related inpatient admissions and emergency room (ER) visits for schizophrenia patients who were treated with a stable dose versus those who experienced a dose reduction of an oral antipsychotic monotherapy

  • Dose reduction has been recommended to manage tardive dyskinesia (TD) in previous practice guidelines for patients with schizophrenia who require maintenance antipsychotic treatment [5, 6], our results suggest that even relatively modest reductions in antipsychotic dosing, regardless of the rationale, may have significant adverse effects on outcomes for some patients

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Summary

Introduction

Data are limited on the benefits and risks of dose reduction in managing side effects associated with antipsychotic treatment. Antipsychotic dose reduction has been recommended in the management of tardive dyskinesia (TD), yet the benefits of lowering doses are not well studied. Stable maintenance treatment is essential to prevent deterioration and relapse in schizophrenia. Management options include discontinuation of the current antipsychotic, switching to a different drug, or lowering the dose [2,3,4]. Tardive dyskinesia (TD), which occurs in up to 30% of patients receiving antipsychotics, is a serious side effect of antipsychotics for which dose reduction has been proposed [2,3,4]. Maintenance antipsychotic treatment is essential to prevent deterioration and relapse [9]. Antipsychotic discontinuation, which is associated with increased risk of violence, incarceration, hospitalization, increased healthcare resource utilization, and interruption of rehabilitation efforts, may be impractical in most patients with schizophrenia [12, 13]

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