- A University of Pittsburgh study used Truveta Data to compare mortality risk across four antipsychotics commonly used off label to treat Alzheimer’s disease.
- Among 17,004 patients with Alzheimer’s disease, mortality risk differed across medications in several head-to-head comparisons.
- Aripiprazole and quetiapine were associated with lower mortality than olanzapine and risperidone in several comparisons.
- The study also found that patient characteristics, including medication use for the treatment of type 2 diabetes, may influence relative mortality risk.
A recent study from University of Pittsburgh researchers found that mortality risk may differ across second-generation antipsychotics commonly used off label in the treatment of Alzheimer’s disease.
Published in CNS Drugs, the study used Truveta Data to analyze 17,004 patients with Alzheimer’s disease who initiated aripiprazole, olanzapine, quetiapine, or risperidone. The study found that aripiprazole and quetiapine were associated with lower mortality than olanzapine and risperidone in several head-to-head comparisons. It also found that mortality differences may vary across patient groups, including patients using medications for the treatment of type 2 diabetes.
These medications are often used off label to manage behavioral and psychological symptoms in Alzheimer’s disease, including psychosis, but their use in older adults with dementia has long raised serious safety concerns. Antipsychotic use in older adults with dementia carries an FDA black box warning because of increased mortality risk.
A difficult treatment decision with limited real-world evidence
Behavioral symptoms in Alzheimer’s disease can be distressing for patients, families, and caregivers. When non-drug approaches are not enough to address these symptoms, clinicians may consider antipsychotic treatment despite known risks.
That makes the choice of medication important. Much of the prior evidence has compared antipsychotic use with placebo or nonuse, but clinicians often need to choose among available medications. This study used real-world data to compare those options directly.
Mortality risk differs across medications
Among patients with Alzheimer’s disease who started one of the four antipsychotics, mortality risk differed by medication.
Aripiprazole was associated with lower mortality than olanzapine and quetiapine. Quetiapine was associated with lower mortality than olanzapine and risperidone. The comparison between aripiprazole and risperidone also favored aripiprazole, though that finding was not statistically significant in the main analysis.
Risk may vary by patient characteristics
The study also asked a more nuanced question, exploring whether mortality risk differs by patient, not only by medication.
This is important in Alzheimer’s disease, where patients often have multiple comorbidities and overlapping medications. In this analysis, patients using medications for type 2 diabetes emerged as one subgroup where mortality patterns differed. Among these patients, aripiprazole was associated with lower mortality compared with a combined group of quetiapine and risperidone.
What this study means for clinical decision-making
This study adds real-world evidence to a difficult treatment decision in Alzheimer’s care. When antipsychotic treatment is considered necessary, mortality risk may differ not only by medication, but also by patient characteristics.
The study does not prove that one antipsychotic is safest for every patient. The findings are observational and may be influenced by factors not fully captured in the data, such as symptom severity, prescribing rationale, dose, or adherence.
For providers, the findings support a more individualized approach to prescribing when antipsychotic treatment is considered necessary. For patients and caregivers, they highlight why the choice of medication, not just the decision to use an antipsychotic, should be part of the risk-benefit conversation.
