Risk of Mortality Among Individual Antipsychotics in Patients With Dementia

Abstract

Objective The use of antipsychotics to treat the behavioral symptoms of dementia is associated with increased mortality. However, there remains limited information regarding individual agents’ risks. Method This was a retrospective cohort study using national data from the US Department of Veterans Affairs (fiscal years 1999–2008) for patients ≥65 years old with dementia, beginning outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, and haloperidol) or valproic acid and its derivatives (as a non-antipsychotic comparison). The total sample included 33,604 patients. Individual drug groups were compared for 180-day mortality rates. Potential confounding was addressed using multivariate models and propensity adjustments. Results In covariate-adjusted intent to treat analyses, haloperidol users had the highest mortality rates (relative risk 1.54, 95% confidence interval 1.38–1.73) followed by risperidone (reference), olanzapine (RR 0.99, 95% CI 0.89–1.10), valproic acid and its derivatives (RR 0.91, 95% CI 0.78–1.06) and quetiapine (RR 0.73, 95% CI 0.67–0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage showed similar patterns. Haloperidol risk was highest in the first 30 days and then significantly and sharply decreased. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during 180-day follow-up. Conclusions There may be differences in mortality risks among individual antipsychotic agents. Further, the use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

Pharmacological management of behavioral symptoms associated with dementia

“…Kales et al [46] in an outpatient study comparing the mortality risk of different psychotropics suggested that haloperidol had the highest risk in the first 30 d and quetiapine the lowest. Additionally, the highest mortality risk for risperidone, olanzapine, quetiapine, and valproate is in the first 120 d of use.…”

Non-pharmacological interventions for aggression in persons with dementia: A 10-year follow-up review of the literature

“…[17] Medications often result in adverse effects such as increased risk of mortality, excessive sedation, increased risk of falls, lethargy, and disorientation. [18][19][20][21][22] 1.3 Rationale for non-pharmacological approaches The use of psychotropic medications to reduce aggression overlooks the possibility that aggression may be related to environmental factors and may serve a communicative function for the PWD. For example, aggressive behaviors occur most frequently during ADLs such as bathing, dressing, and toileting, which naturally involve physical touch from a caregiver.…”

Management of Patients With Alzheimer’s Disease

“…Длительное наблюдение пациентов, страдающих БА и принимающих антипсихотические средства, показывает, что они умирают быстрее, чем остальные пациенты [19,20]. Назначение нейролептиков наиболее опасно пациентам с БА, страдающим сердечно-сосудистыми и легочными заболеваниями.…”