title: Risk of Mortality Among Patients Treated With Antipsychotic Medications: A Nationwide Population-Based Study in Taiwan.
abstract: In this nationwide population-based study, we examined whether haloperidol exposure is associated with a higher risk of mortality than are other antipsychotic medications. Patients who newly received monotherapy with chlorpromazine (n = 2133), haloperidol (n = 4454), quetiapine (n = 1513), and risperidone (n = 1046) between January 1, 2001, and December 31, 2011, were selected from a random sample of the 1 million enrollees of the Taiwan National Health Insurance Research Database. The association between antipsychotic prescription and mortality was estimated through Cox proportional hazard regression. To examine the mortality rates of antipsychotics at different exposure durations, we compared the differences among short-term (≤30 days), midterm (31-90 days), and long-term (>90 days) antipsychotic use. The mortality rates during the follow-up among the chlorpromazine, haloperidol, quetiapine, and risperidone groups were 17.4%, 45.5%, 26.8%, and 25.9%, respectively. The mortality risk among patients receiving haloperidol was the highest within 30 days of the prescription, after which the risk reduced rapidly. Compared with the patients receiving chlorpromazine, the mortality risk was higher in short-term (adjusted hazard ratio, 2.11; 95% confidence interval, 1.87-2.39) and midterm haloperidol users (1.86; 1.54-2.25) than in long-term users (0.99; 0.61-1.61). In conclusion, haloperidol use is associated with higher mortality risk than other antipsychotic medications. The mortality risk varies according to the duration of drug exposure. Underlying characteristics and medical conditions may influence the estimation of the mortality risk. Clinicians should pay attention to the mortality risk when prescribing antipsychotic medications, particularly for the elderly and critically ill patients.
authors.affiliation: From the *Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine; †Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; ‡Institute of Statistical Science, Academia Sinica; §Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica; ∥Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei; ¶Community Medicine Research Center, Chang-Gung Memorial Hospital, Keelung, Taiwan; #Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX; and **Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Liang-Jen
authors.initials: LJ
authors.lastname: Wang
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Lee
authors.forename: Shin-Sheng
authors.initials: SS
authors.lastname: Yuan
authors.forename: Kang-Chung
authors.initials: KC
authors.lastname: Yang
authors.forename: Chun-Ju
authors.initials: CJ
authors.lastname: Yang
authors.forename: Tung-Liang
authors.initials: TL
authors.lastname: Lee
authors.forename: Yu-Chiau
authors.initials: YC
authors.lastname: Shyu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects*; D016638:Critical Illness; D005260:Female; D005500:Follow-Up Studies; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D000069348:Quetiapine Fumarate / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects*; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000069348:Quetiapine Fumarate; D006220:Haloperidol; D018967:Risperidone; D002746:Chlorpromazine