High‐dose antipsychotic use in schizophrenia: a comparison between the 2001 and 2004 Research on East Asia Psychotropic Prescription (REAP) studies
Authors: Sim Kang , Su Hsin Chuan , Fujii Senta , Yang Shu‐yu , Chong Mian‐Yoon , Ungvari Gabor , Si Tianmei , He Yan Ling , Chung Eun Kee , Chan Yiong Huak , Shinfuku Naotaka , Kua Ee Heok , Tan Chay Hoon , Sartorius Norman 
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• High‐dose antipsychotic use in schizophrenia has been a topic of continuous debate since the introduction of the first antipsychotic in the 1950s.

• There are reasons arguing for (such as pharmacokinetic reasons for the possible use of high antipsychotic doses in those with genetic polymorphisms associated with unusually high metabolic rates and the presence of inducers such as co‐prescriptions of other medications and smoking) and against high‐dose antipsychotic use (such as the pharmacokinetic understanding that Asians may need lower antipsychotic doses, the association of high antipsychotic doses with more frequent adverse effects, and receptor occupancy data from neuroimaging studies).

• There is increasing awareness of the need for more practice‐based research in order to highlight discrepancies between the empirical data and clinical practice.

WHAT THIS STUDY ADDS

• There was an overall significant decrease in the frequency of high‐dose antipsychotic use from 17.9% in 2001 to 6.5% in 2004 within East Asia.

• The association of high antipsychotic doses with demographic, psychopathological and treatment variables identified the clinical profile of schizophrenia patients who are at risk of receiving high antipsychotic doses.

• These findings provide information and impetus for clinicians to constantly monitor the drug regimes and to foster rational, evidence‐based prescribing practices.

AIMS

We aimed to examine the frequency of high‐dose (defined as mean chlorpromazine mg equivalent doses above 1000) antipsychotic prescriptions in schizophrenia and their clinical correlates in the context of a comparison between studies in 2001 and 2004 within six East Asian countries and territories.

METHODS

Prescriptions of high‐dose antipsychotic for a sample of 2136 patients with schizophrenia from six countries and territories (mainland China, Hong Kong, Korea, Japan, Taiwan and Singapore) were evaluated in 2004 and compared with data obtained for 2399 patients in 2001.

RESULTS

Overall, the comparison between 2001 and 2004 showed a significant decrease in high‐dose antipsychotic use from 17.9 to 6.5% [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.26, 0.39, P < 0.001]. Patients who received high‐dose antipsychotics were significantly more likely to have multiple admissions (OR 1.96, 95% CI 1.16, 3.33, P = 0.009), more positive psychotic symptoms such as delusions (OR 2.05, 95% CI 1.38, 3.05, P < 0.001) and hallucinations (OR 1.85, 95% CI 1.30, 2.64, P = 0.001), but less likely to have negative symptoms (OR 0.58, 95% CI 0.40, 0.82, P = 0.002). Multivariate regression analyses revealed that prescription of high‐dose antipsychotics was also predicted by younger age (P < 0.001), time period of study (2001; P < 0.001), use of first‐generation antipsychotic (P < 0.001) and depot antipsychotics (P < 0.001) as well as antipsychotic polytherapy (P < 0.001).

CONCLUSIONS

We identified the clinical profile and treatment characteristics of patients who are at risk of receiving high antipsychotic doses. These findings should provide impetus for clinicians to constantly monitor the drug regimes and to foster rational, evidence‐based prescribing practices.