Below, we discuss the drugs used to treat behavioral problems in dementia, evidence for the efficacy of these drugs, and their potential for adverse effects.
ANTIPSYCHOTIC DRUGS: SMALL BENEFIT, BIG RISK
Although antipsychotic drugs, both typical and atypical, are often used to treat dementia- related behaviors, their beneficial effects are minimal and adverse effects are common. 8,9
Aggression has been considered a symptom that might respond to an atypical antipsychotic drug. 10 However, the Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer’s Disease (CATIE-AD) trial 11 found no differences in efficacy between placebo and the atypical antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) in treating psychosis, aggression, and agitation in dementia. In that study, rates of drug discontinuation due to adverse effects ranged from 5% for placebo to 24% for olanzapine. Overall, 82% of the patients stopped taking their initially assigned medications during the 36-week period of the trial. 11
Antipsychotic drugs may cause more adverse effects in patients with Parkinson disease or dementia with Lewy bodies, and medications with the least dopamine D2 receptor blockade are chosen to reduce the impact on the parkinsonism. Patients with movement disorders were excluded from the CATIE-AD study, and data on this topic are very limited. Quetiapine and olanzapine are often used as alternatives to clozapine (Clozaril) for treating psychosis in Parkinson disease and may have a role in dementia with Lewy bodies. 12,13
Atypical antipsychotics carry significant risk of illness and even death. The US Food and Drug Administration (FDA) has published advisories about hyperglycemia, cerebrovascular events, and death. 14 Returning to the older, “typical” antipsychotics is not a solution either, given their high incidence of extrapyramidal symptoms 15 and potentially higher risk of death. 16,17
Even if effective, try stopping the drug
Even in the few situations in dementia in which antipsychotics prove efficacious, a trial of dose-reduction and possible discontinuation is a part of the appropriate plan of care. Symptoms such as aggression and delusions may decrease as the underlying dementia progresses. 2 A consensus statement on antipsychotic drug use in the elderly 18 recommended stopping antipsychotic drugs as follows:
- If given for delirium—discontinue the drug after 1 week
- For agitated dementia—taper within 3 to 6 months to determine the lowest effective maintenance dose
- For psychotic major depression—discontinue after 6 months
- For mania with psychosis—discontinue after 3 months. 18
Disorders for which antipsychotics are not recommended are irritability, hostility, generalized anxiety, and insomnia. In contrast with recommendations for dementia-related behaviors, the psychosis of schizophrenia is treated lifelong at the lowest effective dose of medication.
ANTIDEPRESSANTS: MANY CHOICES, LITTLE EVIDENCE
Depression is hard to assess in a patient with dementia, particularly since apathy is a common symptom in both dementia and depression and may confuse the presentation. Additionally, screening tests for depression have not been validated in the demented elderly.
Depression in dementia is associated with poorer quality of life, greater disability in activities of daily living, a faster cognitive decline, a high rate of nursing home placement, a higher death rate, and a higher frequency of depression and burden in caregivers. 19 Quality of life may improve with antidepressant treatment even if the patient does not meet all the criteria for a major depressive disorder. Provisional recommendations for diagnosing depression in dementia suggest using three (instead of five) or more criteria, and include irritability or social isolation as additional criteria. 20