Long-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia

Veterans Affairs (VA) New England Mental Illness, Research Education and Clinical Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
New England Journal of Medicine (Impact Factor: 55.87). 03/2011; 364(9):842-51. DOI: 10.1056/NEJMoa1005987
Source: PubMed


BACKGROUND Long-acting injectable risperidone, a second-generation antipsychotic agent, may improve adherence to treatment and outcomes in schizophrenia, but it has not been tested in a long-term randomized trial involving patients with unstable disease. METHODS We randomly assigned patients in the Veterans Affairs (VA) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of long-acting injectable risperidone every two weeks or to a psychiatrist's choice of an oral antipsychotic. All patients were followed for up to 2 years. The primary end point was hospitalization in a VA or non-VA psychiatric hospital. Symptoms, quality of life, and functioning were assessed in blinded videoconference interviews. RESULTS Of 369 participants, 40% were hospitalized at randomization, 55% were hospitalized within the previous 2 years, and 5% were at risk for hospitalization. The rate of hospitalization after randomization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics (39% after 10.8 months vs. 45% after 11.3 months; hazard ratio, 0.87; 95% confidence interval, 0.63 to 1.20). Psychiatric symptoms, quality of life, scores on the Personal and Social Performance scale of global functioning, and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments. Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms. CONCLUSIONS Long-acting injectable risperidone was not superior to a psychiatrist's choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization, and it was associated with more local injection-site and extrapyramidal adverse effects.

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    • "The ASI was a proportion ranging from 0 to 1 with higher scores indicating more severe substance use problems. The CGI score was measured on a scale of 1 to 7, with higher scores indicating poorer functioning or less improvement [7]. "
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    ABSTRACT: Missing data pose a serious challenge to the integrity of randomized clinical trials, especially of treatments for prolonged illnesses such as schizophrenia, in which long-term impact assessment is of great importance, but the follow-up rates are often no more than 50%. Sensitivity analysis using Bayesian modeling for missing data offers a systematic approach to assessing the sensitivity of the inferences made on the basis of observed data. This paper uses data from an 18-month study of veterans with schizophrenia to demonstrate this approach. Data were obtained from a randomized clinical trial involving 369 patients diagnosed with schizophrenia that compared long-acting injectable risperidone with a psychiatrist's choice of oral treatment. Bayesian analysis utilizing a pattern-mixture modeling approach was used to validate the reported results by detecting bias due to non-random patterns of missing data. The analysis was applied to several outcomes including standard measures of schizophrenia symptoms, quality of life, alcohol use, and global mental status. The original study results for several measures were confirmed against a wide range of patterns of non-random missingness. Robustness of the conclusions was assessed using sensitivity parameters. The missing data in the trial did not likely threaten the validity of previously reported results. Copyright © 2014 John Wiley & Sons, Ltd.
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    • "However, the results from randomized controlled trials and reviews on this subject give a mixed picture. For example, a recent large randomized controlled trial has shown that there was no statistically significant difference between risperidone long-acting injection and an oral formulation in preventing hospitalization.40 A meta-analysis based on 21 randomized controlled studies with the primary outcome measure of study-defined relapse at the longest time point in the study, found that long-acting injections were not significantly superior to oral antipsychotics. "
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    • "However, the majority of studies evaluating the safety and efficacy of these medications are typically 1 year or less in duration (Leucht et al., 2011; Kishimoto et al., 2014). Although there are some clinical trials on long-acting injectable antipsychotics that are 2 years in duration (Hogarty et al., 1979; Macfadden et al., 2010; Detke et al., 2014; Lambert et al., 2011; Rosenheck et al., 2011), few studies have examined these medications for longer durations. As schizophrenia is often a lifelong disorder, and as long-acting injectable treatments in schizophrenia are intended for long-term use, there is need for longer term data. "
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