Elsevier

Journal of Psychiatric Research

Volume 95, December 2017, Pages 299-307
Journal of Psychiatric Research

Risperidone versus olanzapine among patients with schizophrenia participating in supported employment: Eighteen-month outcomes

https://doi.org/10.1016/j.jpsychires.2017.09.008Get rights and content

Abstract

This study compares the efficacy and tolerability of olanzapine versus risperidone among patients with schizophrenia who are established in outpatient psychiatric care and entering supported employment. A multicenter, randomized, double-blind trial was conducted among 107 outpatients with schizophrenia, who were cross-titrated to flexible dose risperidone or olanzapine over 2 weeks. Clinical endpoints included time to hospitalization and persistence on assigned medication. Weight, laboratory tests, psychopathology, neurologic side effects, social adjustment and role functioning were assessed at 3–6 month intervals. Data were analyzed first by randomized treatment, and then reassessed controlling for prior medication treatment. The proportion of patients on assigned medication at 18 months was 30.9% for risperidone and 37.3% for olanzapine. Mean doses were 6.4 ± 3.2 mg daily for risperidone, and 17.0 ± 5.0 mg daily for olanzapine. The groups did not differ significantly in time to medication discontinuation, first hospitalization or first employment. There were few differences in psychopathology, laboratory, or neurological assessments between groups at 18 months. Patients randomized to olanzapine gained modestly more weight. Controlling for pre-randomization medication suggested improvement in some aspects of psychopathology from switching medications; however, switching from olanzapine to risperidone was associated with more hospitalizations. Risperidone and olanzapine have similar efficacy and tolerability in patients with schizophrenia who are participating in supported employment. Randomization to olanzapine was associated with more weight gain, but randomization from olanzapine to risperidone appeared to be associated with a greater likelihood of hospitalization. Careful monitoring of metabolic effects and participation in supported employment may have contributed to minimal weight gain and metabolic effects.

Introduction

Guiding outpatients with schizophrenia in choosing optimal antipsychotic therapy for participating in psychosocial rehabilitation is complex and poorly understood (Salkever et al., 2006, Sungur et al., 2011). Antipsychotic medications may be associated with side effects such as sedation and EPS that can interfere with attention, learning and motor function (Kumar et al., 2013). There is some evidence that antipsychotics may have differential effects on cognitive function (Bilder et al., 2002, Keefe et al., 2007, Matsuda et al., 2014). Switching antipsychotic medications can also be disruptive and destabilizing (Takeuchi et al., 2017).

Large randomized trials such as the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study have demonstrated that the second-generation antipsychotics (SGAs) as a group have similar effects on psychopathology, with some advantages in treatment outcomes for clozapine, olanzapine, and risperidone (Lieberman et al., 2005, McEvoy et al., 2007, McEvoy et al., 2006, Stroup et al., 2006). However, the agents also differed in their side effects. A re-analysis of the CATIE phase 1 findings by Essock and colleagues (Essock et al., 2006) found that patients who were randomized to the same antipsychotic that they were taking before study entry tended to have better outcomes than those who were randomly assigned to take a different antipsychotic medication during the study. However, the authors did not evaluate the effects of continuing or changing antipsychotics on adverse effects. All of these medication effects were studied in isolation from any psychosocial rehabilitation that patients were receiving.

In the current trial, stable, unemployed outpatients with schizophrenia were randomly assigned to an 18-month double-blind comparison of olanzapine and risperidone at the point of initiating a supported employment program (Glynn et al., 2017). The purpose of this study was to compare two highly prescribed antipsychotic medications in the understudied clinical context of psychosocial rehabilitation. We examined the effectiveness, but also the side effects, of assigned medication treatment as a function of prior antipsychotic treatment.

Section snippets

Study setting and design

We randomized 107 stable outpatients to double-blind risperidone vs. olanzapine. In addition, all participants received supported employment using the evidence-based Individual Placement and Support Program (IPS)(Becker and Drake, 1994), and half of these participants were randomly assigned to receive vocational maintenance skills training in the clinic (Glynn et al., 2017, Mueser et al., 2005). Patients were recruited from a Dartmouth-affiliated Community Mental Health Center (NH site) and an

Randomized medication group analysis (Two groups)

The demographic composition of the sample is presented in Table 1. There were no differences in any of the demographic variables between the two randomized treatment groups. There was a significant difference in pre-randomization medication by site, with patients recruited in LA more often taking risperidone, and patients recruited in NH more often taking olanzapine. There were also site differences in race, gender, education and prior psychiatric hospitalizations (Glynn et al., 2017).

Discussion

The primary analysis comparing the 2 randomized treatment groups confirmed our hypothesis that risperidone and olanzapine have similar effectiveness in the context of supported employment. The low 18-month assigned medication continuation rates, consistent with those found in CATIE phase-1 (Lieberman et al., 2005), are somewhat surprising in this study where participants were actively involved in psychosocial rehabilitation. Study physicians were actively working with rehabilitation staff to

Conflict of interest

Dr. Noordsy receives research support from Janssen. Dr. Marder (R092670SCH3013) serves on the consulting and advisory boards of Abbvie, Allergan, Lundbeck, Otsuka, Roche, Takeda, and Teva and receives research support from Forum (20152534) and Neurocrine (NBI-98854-1506). Drs. Sugar and Glynn, and Mr. O'Keefe report no competing interests.

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