High rates of prior antipsychotic use (within 30 days of starting study medication) were observed: 90.7% for patients in the lurasidone group (pooled), 91.0% for patients in the risperidone group, and 81.8% for patients in the quetiapine XR group (Table 3). No patients had taken clozapine for at least 30 days before study entry. The distribution of patients who had taken other antipsychotic agents associated with increased risk of weight gain (e.g. olanzapine, quetiapine) was similar across the pooled treatment groups, except for a lower rate of prior quetiapine use in the lurasidone and quetiapine groups compared with the risperidone group. Across the 12-month study period, the mean modal daily doses of study medication were 90.6 mg lurasidone, 4.4 mg risperidone, and 660.6 mg quetiapine XR.
Younger, treatment-naive patients and patients belonging to certain racial and ethnic groups (e.g. black and Hispanic patients) appear to be at greater risk for antipsychotic-related weight gain (Meyer et al., 2009; Salimi et al., 2009; Maayan and Correll, 2011). In the present analysis, younger age was significantly associated with weight gain during lurasidone treatment; however, weight gain of at least 7% was observed in a similar proportion of white patients and black patients taking lurasidone for 12 months. Asian patients (particularly Asian women) were significantly more likely than patients of other races to experience at least 7% weight gain, which is consistent with previous reports that Asian patients may be more likely to experience adverse effects of antipsychotic medications (Bond, 1991). Genetic factors may account for differences in medication-related weight gain based on race or ethnicity (Lett et al., 2012). A recent meta-analysis found a significant association between the leptin −2548A allele and the risk for antipsychotic-induced weight gain in Asian patients with schizophrenia (Shen et al., 2014).
This analysis has several limitations, including its post-hoc nature and the lack of a placebo control group. This observed-case analysis included only patients who completed 12 months of treatment. The number of patients treated with quetiapine XR for 12 months (N=33) was relatively small compared with the other treatment groups. Between-group differences in dropout rates could have influenced the magnitude of weight change observed at month 12, to the extent that treatment discontinuation was associated with weight change; however, the proportion of patients in the underlying studies who discontinued study medication was similar for lurasidone, risperidone, and quetiapine XR. In addition, detailed information was not collected with regard to prior antipsychotic treatment (e.g. dose, duration of treatment, impact on weight). Thus, the magnitude of antipsychotic-induced weight gain that may have occurred before the patients’ enrollment in the studies included in this analysis is unknown. The effect of antipsychotic medication dose on weight gain was not evaluated in this analysis because five of six longer-term studies used flexible dosing.
Nancy Holland, PhD, Synchrony Medical Communications, LLC, provided medical writing and editorial assistance for this manuscript under the direction of the authors. Financial support for this writing and editorial assistance from Synchrony Medical Communications, LLC, were provided by Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA. Clinical research was sponsored by Sunovion Pharmaceuticals Inc. The sponsor was involved in the study design, data collection, and analysis of data.
The studies and this analysis were sponsored by Sumitomo Dainippon Pharma Co. Ltd., Osaka, Japan, and Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA, a wholly-owned US subsidiary of Sumitomo Dainippon Pharma Co Ltd. Dr Meyer reports having received research support from Bristol-Myers Squibb, National Institutes of Health (as General Clinical Research Center support), National Institute of Mental Health, and Pfizer Inc., and speaking or advising fees from Alkermes, Arbor Scientia, Bristol-Myers Squibb Company, Forum Pharmaceuticals Inc., Genentech, Neuroscience Education Institute, Otsuka America Inc., and Sunovion Pharmaceuticals Inc. Drs Mao, Pikalov, Cucchiaro, and Loebel are employees of Sunovion Pharmaceuticals Inc.
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