The Influence of Antipsychotics on Diabetes Mellitus and Fracture Risks in Schizophrenic Patients
Date Issued
2010
Date
2010
Author(s)
Cho, Yi-Tzu
Abstract
Background: Second-generation antipsychotics (SGAs), have been demonstrated efficacy in the treatment of schizophrenia with fewer extrapyramidal system side effects than first-generation antipsychotics (FGAs), and accordingly have also been approved as the first-line drugs in treating schizophrenia. However, recent studies found that schizophrenic patients have higher risk for diabetes mellitus (DM) and low bone mineral density, it is speculated that in addition to the disease of schizophrenia itself, the use of antipsychotics may also affect the blood sugar control and bone health, especially the second-generation antipsychotics. There is no national study examing the effects of antipsychotics on DM and fracture risks so far in Asia; therefore, we conducted the current study to provide a reference for clinical medical staffs in selecting drugs.
Objectives: To compare the DM and fracture events rate between schizophrenic patients and non-psychiatric population; and to assess the DM and fracture risks between different antipsychotics in patients with newly diagnosed schizophrenia.
Methods: This was a retrospective cohort study. We used a subset database (LHID2005) retrieved from National Health Insurance Research Database (NHIRD) to establish a cohort of patients with new onset of schizophrenia from 2001 to 2008, and screening for non-psychiatric population according to DM and fracture study groups.
Descriptive analysis. We compared the DM and fracture event rate and age of onset between schizophrenic patients and non-psychiatric population. The DM and fracture study groups were divided into two groups (Schizo-A group and Schizo-N group), according to the exposure of antipsychotics, and then compared the demographic and clinical characteristics between the two groups.
Survival analysis. Our study endpoints were DM, fracture at all sites and each part. We used time-dependent Cox’s proportional hazard model to evaluate the hazard ratio (HR) of all FGAs and individual SGAs for each study endpoints.
Results: A total of 2649 new onset schizophrenic patients were included in the DM cohort (DM-Schizo group), and 9925 matched non-psychiatric reference were randomly selected (DM-Refere group). The crude DM event rates were 7.1% and 3.7%, and average DM onset ages were 49.1 y/o and 55.5 y/o in DM-Schizo group and DM-Refere group, respectively (p<0.0001). There were 2414 patients in DM-Schizo-A group and 235 in DM-Schizo-N group; DM-Schizo-A group mainly concentrated in 11-50 y/o, but the age distribution of DM-Schizo-N group is more dispersed. Compared with DM-Schizo-N group, patients in DM-Schizo-A group treated with more lithium and valproate, and had higher prevalence of episodic mood disorders. After adjusted with confounding factors, patients exposed to FGAs and amisulpride were more likely to have DM (FGAs HR=1.44; amisulpride HR=2.37). The higher accumulative dose of amisulpride, risperidone and ziprasidone were associated with a higher risk of DM (amisulpride HR=1.005; risperidone HR=1.002; ziprasidone HR=1.007).
A total of 2501 new onset schizophrenic patients were included in the fracture cohort (FRA-Schizo group), and 9009 matched non-psychiatric reference were randomly selected (FRA-Refere group). The crude fracture event rates were 8.0% and 4.7 % in FRA-Schizo group and FRA-Refere group, respectively (p<0.0001). There were 2284 patients in FRA-Schizo-A group and 217 in FRA-Schizo-N group; FRA-Schizo-A group mainly concentrated in 11-50 y/o, but the age distribution of FRA-Schizo-N group is more dispersed. Compared with FRA-Schizo-N group, patients in FRA-Schizo-A group treated with more lithium, BZD, anti-depressants and anti-convulsants, and had higher prevalence of episodic mood disorders and Parkinson''s disease. After adjusted with confounding factors, patients exposed to any kinds of antipsychotics were not associated with the occurrance of fracture at all sites. However, patients exposed to ziprasidone was associated with a higher risk of neck/trunk fracture (HR=5.44, CI=1.67-17.76, p=0.0051). Risperidone was associated with a lower risk of lower limb fracture (HR=0.58, 95% CI=0.34-0.99, p=0.0473). The higher accumulative dose of aripiprazole and zotepine were associated with a higher risk of vertebral fracture (HR are both 1.002).
Conclusions: The DM and fracture events rate are higher in schizophrenic patients than in non-psychiatric population, and the DM onset age was lower in schizophrenic patients. In both DM and fracture study population, there were some demographic and clinical characteristics differences between Schizo-A group and Schizo-N group. Different from previous study, the use of FGAs and amisulpride were found to be associated with significant increased risk of DM in our study; and the higher accumulative dose of amisulpride, risperidone and ziprasidone were also associated with a higher risk of DM. All antipsychotics seem not to be associated with the risk of fracture at all sites, but ziprasidone was associated with a higher risk of neck/trunk fracture, and the accumulative dose of aripiprazole and zotepine were also associated with a higher risk of vertebral fracture. However, risperidone seems to have a protective effect in lower limb fracture in our study.
Subjects
schizophrenia
antipsychotics
diabetes mellitus
fracture
SDGs
Type
thesis
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