ABSTRACT
Objective@#The relationship of antipsychotics and the risk of refracture in treated patients is unclear. The aim of this study is to evaluate the association between prolonged antipsychotic and the incidences of bone fractures and refractures in schizophrenia. @*Methods@#This is a retrospective nested case-control study using Taiwan National Health Insurance Research Database recorded from 2000 to 2005, with cases followed up to end of 2011. Total of 7,842 schizophrenic patients, 3,955 had developed bone fractures were compared with 3,887 control subjects matched in age, sex, and index date.Antipsychotic drug exposure was classified based on the drug type and medication duration. Conditional logistic regression analyses were performed. Odds ratio (OR) and confidence interval (CI) were calculated. @*Results@#We found (after adjustments) higher risks of developing fractures under continued use of typical (OR = 1.70; 95% CI, 1.51−1.91) or atypical antipsychotics (OR = 1.43; 95% CI, 1.28−1.60) were found. Additionally, continued use typical (OR = 1.84; 95% CI, 1.35−2.50) or atypical antipsychotics (OR = 1.44; 95% CI, 1.06−1.95) was positively associated with refracture risks. Moreover, refractures were associated with continuous use of chlorpromazine (one typical antipsychotics, OR = 2.45; 95% CI, 1.14−5.25), and risperidone (OR = 1.48; 95% CI, 1.01−2.16) or zotepine (OR = 2.15; 95% CI, 1.06−4.36) (two atypical antipsychotics). @*Conclusion@#Higher risks of bone fracture and refracture were found in schizophrenia under prolonged medication with typical or atypical antipsychotics. We therefore recommend that clinicians should pay more attention on bone density monitoring for patients using long-term antipsychotics.
ABSTRACT
OBJECTIVE: Metabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-alpha/PPAR-gamma heterodimers. We examined a possible role of the PPAR-gamma gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics. METHODS: Single nucleotide polymorphisms (SNPs) of the PPAR-gamma gene and a serial of metabolic traits were determined in 394 schizophrenia patients, among which 372 were rated with Positive and Negative Syndrome Scale (PANSS). RESULTS: SNP-10, -12, -18, -19, -20 and -26 were associated with glycated hemoglobin (HbA1c) whereas SNP-18, -19, -20 and -26 were associated with fasting plasma glucose (FPG). While SNP-23 was associated with triglycerides, no associations were identified between the other SNPs and lipids. Further haplotype analysis demonstrated an association between the PPAR-gamma gene and psychosis profile. CONCLUSION: Our study suggests a role of the PPAR-gamma gene in altered glucose levels and psychosis profile in schizophrenia patients exposed to antipsychotics. Although the Pro12Ala at exon B has been concerned an essential variant in the development of obesity, the lack of association of the variant with metabolic traits in this study should not be treated as impossibility or a proof of error because other factors, e.g., genes regulated by PPAR-gamma, may have complicated the development of metabolic abnormalities. Whether the PPAR-gamma gene modifies the risk of metabolic abnormalities or psychosis, or causes metabolic abnormalities that lead to psychosis, remains to be examined.