Aripiprazole in the treatment of Alzheimer's disease

Psychosis is a common and difficult to treat symptom in Alzheimer's disease (AD). It is a cause of diminished quality of life and caregiver distress. Atypical antipsychotics are frequently used for the treatment of dementia-related psychosis, despite FDA warnings because of increased mortality associated with the use of these medications in dementia patients. Aripiprazole is a newer atypical antipsychotic drug with partial agonist activity at dopamine receptors and antagonist activity at 5-HT(2A) receptors, with a low side-effect profile.

This descriptive review gives a short overview of the pathology and epidemiology of AD, including psychotic symptoms, and describes the mode of action of aripiprazole and results of preclinical studies. Finally, randomized controlled trials evaluating the use of aripiprazole in AD-related psychosis and agitation are discussed. Whenever relevant, meta-analytical data from literature are referred to.

In randomized placebo-controlled clinical trials, aripiprazole shows modest efficacy in the treatment of AD-related psychosis. Neuropsychiatric symptoms alleviated were predominantly psychotic features and agitation. In individual trials, aripiprazole was generally well tolerated, serious side effects were seldom reported and included accidental injury and somnolence. Meta-analyses however demonstrated increased mortality as a class effect for atypical, but also for typical antipsychotics. No increased cardiovascular outcomes, cerebrovascular accidents, increased appetite or weight gain were demonstrated in meta-analyses for aripiprazole-treated patients with psychosis of dementia. Aripiprazole was found to induce sedation. Aripiprazole should only be used in selected patient populations resistant to non-pharmacological treatment with persisting or severe psychotic symptoms and/or agitation, and in which symptoms lead to significant morbidity, patient suffering and potential self-harm. The indication for continuing treatment should be revised regularly.