Abstract
BackgroundIn a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes.MethodsOutpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140), "medium" (405 mg/4 weeks; N = 318), or "high" (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data).ResultsSafety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose.ConclusionsAnalyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient.Trial RegistrationClinicalTrials.gov: NCT00088491
Highlights
In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al, 2010), apparent dose-associated changes were noted in both efficacy and safety parameters
Some previous studies in patients treated with oral olanzapine have found an association between olanzapine plasma concentrations and changes in some metabolic parameters [3,4], as well as differences in changes in efficacy and safety parameters in a sample including patients treated with doses greater than 20 mg/day [5]
Significant dose-associated changes were identified for weight and for prolactin, both of which exhibited mean increases with increasing dose
Summary
In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al, 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. Some previous studies in patients treated with oral olanzapine have found an association between olanzapine plasma concentrations and changes in some metabolic parameters [3,4], as well as differences in changes in efficacy and safety parameters in a sample including patients treated with doses greater than 20 mg/day [5]. Considering these reports, the observed dose-associated changes were not completely unexpected and warranted further investigation. Risperidone long-acting injection has been reported as having dose-related changes for both weight and EPS, similar to that seen with oral risperidone [7]. Based on a limited number of studies, paliperidone palmitate may have dose-related changes for weight, EPS, and prolactin [8]
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