Use of antipsychotics and risk of cerebrovascular events in schizophrenic patients – A nested case-control study
Date Issued
2011
Date
2011
Author(s)
Hsieh, Pei-Hua
Abstract
Background: Antipsychotics have been used in treatment of psychological diseases such as schizophrenia, depression and bipolar, as well as in dementia patients with psychosis and behavioural problems. Recent researches indicated an increasing risk of developing cerebrovascular adverse events due to the use of antipsychotics in patients with dementia and elderly users. The risk of antipsychotics on the occurrence of stroke in schizophrenic patients remains unknown. Therefore, we conducted this study to examine the relationship between antipsychotics and risk of stroke among schizophrenic patients, to provide a reference to clinical medical specialists when treating schizophrenic patients.
Objectives: To identify whether the use of antipsychotics increase risk of stroke among newly diagnosed schizophrenic patients, onset of such adverse event, and find out the risk factors that affect the risk of stroke among schizophrenic patients.
Methods: A retrospective nested case-control study was conducted by using the data from two sets of longitudinal health insurance database (LHID 2000 and LHID 2005). Newly diagnosed schizophrenic patients (ICD-9 code=295.xx) between 2001 and 2009 without diagnosis of stroke before first diagnosis of schizophrenia were identified to form the study cohort. The date of first diagnosis of schizophrenia was defined as entry date. Patients with diagnosis of stroke or transient ischemic attack (ICD-9 code=430.xx-435.xx) were defined as the cases, and the date of first diagnosis of stroke was taken as index date for the cases. For each case, two controls were randomly selected from the cohort, matched by age (±2 years) and sex, and were assigned an index date of the corresponding case. The study individuals were divided into three groups based on the use of antipsychotic agents before the index date. Current users were those who had prescription period within 7 days before index date, including index date, recent users were defined as patients with the last prescription period ended within 8 days till 30 days before index date, and past users were those with the prescription period not overlapping the last 30 days before index date. Non-users were defined as patients with no use of antipsychotics during the whole follow-up period. Based on the length of antipsychotic use, the current users were divided into four categories (0–15, 16–30, 31–90 and >90 days) to assess the relationship between length of antipsychotic use and risk of stroke. The type of antipsychotic prescriptions were analyzed by variables of single use of first generation antipsychotics, single use of second generation antipsychotics, and combination of first and second generation antipsychotics, as well as individual antipsychotics. Other potential confounders included co-morbidities and co-medication that related to the risk of stroke. For conducting the basic demographic analysis, we use t-test for continuous variables and Chi-square analysis for discrete variables. We used conditional logistic regressions to examine the relationship between antipsychotic use and risk of stroke.
Results: There were 9715 individuals in newly diagnosed schizophrenic cohort, we identified 386 cases and 772 controls. There were no differences in age, sex and length of follow-up period between two groups, but cases tend to had higher prevalence of co-morbidities and co-medication than controls. After adjustment of potential confounders, current users had increased risk of stroke compared with non-users (adjusted OR: 1.94, 95% CI: 1.11-1.39). Other risk factors included dementia, COPD, hypertension, and concomitant use of anti-platelet drugs, NSAIDs, valproate and phenytoin. The risk of stroke had a temporal relationship with antipsychotic use, which concentrated in the first month of use, with the adjusted OR for the length of antipsychotics used less than 15 days and 16-30 days 9.41 (95% CI: 3.08-28.71) and 6.90 (95% CI: 1.09-43.69), respectively. The effect decreased with the length of antipsychotics used, that risk of stroke did not different from non-user when duration greater than 30 days. Among antipsychotics, risk of stroke increased when patients used first generation antipsychotics alone or combined with second generation antipsychotics, with adjusted OR 2.75 (95% CI: 1.34-5.64) and 2.37 (95% CI: 1.20-4.68), respectively. Uses of chlorpromazine (OR: 9.26, 95% CI: 1.54-55.69), flupentixol (OR: 3.39, 95% CI: 1.22-9.42), haloperidol (OR: 4.74, 95% CI: 1.45-15.47) and prochlorperazine (OR: 9.83, 95% CI: 1.49-65.02) had increased risk of stroke. Uses of risperidone had relative protective effect in stroke, with OR 0.40 (95% CI: 0.20-0.82).
Conclusion: Use of antipsychotics is associated with risk of stroke and transient ischemic attack among schizophrenic patients, with the greatest risk in first month after started antipsychotics. Other risk factors that increase the risk of stroke in schizophrenic patients include diseases that take anti-platelet drugs as standard therapy, dementia, COPD, hypertension, and concomitant use of NSAIDs, valproate and phenytoin. First generation antipsychotics, especially chlorpromazine, flupentixol, haloperidol and prochlorperazine, have increased risk of stroke, with the greatest risk when using prochlorperazine and chlorpromazine. Risperidone seems to have protective effect against stroke, but need further studies to prove it.
Subjects
schizophrenia
antipsychotic
stroke
case-control study
Type
thesis
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