People with Alzheimer’s disease often suffer not only from the debilitating effects of the disease itself, but also from the secondary psychological effects. Delusions and hallucinations appear in up to 50 percent of those with Alzheimer’s, and as many as 70 percent demonstrate aggressive behaviors and agitation. Both caregivers and family members are distressed by these symptoms, and so everyone is motivated to treat the person with Alzheimer’s with antipsychotic medications.
Antipsychotic medications haven’t always been well-researched on older populations, and fewer still on people with a disease like Alzheimer’s. And when the research has been done, the results are often underwhelming.
Take the latest research, for instance, by Vigen and colleagues (2011). In a robust study conducted on “modern” atypical antipsychotic medications, the researchers found that patients on any of the antipsychotic medications tested suffered from a statistically and clinically significant decline on a number of cognitive measures, compared with a placebo control group.
CATIE-AD included 421 outpatients with Alzheimer’s disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), or placebo.
Based on their clinicians’ judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients. […]
Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; –2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer’s Disease Assessment Scale (–4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures.
Despite these cognitive declines, the researchers suggest it still may be preferable to prescribe one of these medications to help control aggressive behavior in a person with Alzheimer’s:
Despite the evidence for worsening cognitive function and other adverse events with antipsychotics, improvement in psychotic and aggressive behavior may still warrant use of these agents in individual cases.
To aid in choosing the best medication for a given patient, the relative adverse effects on cognitive function within this class of medication need to be addressed in further studies that include assessments of attention, psychomotor function, and executive function.
The recommendation shouldn’t be surprising. Here’s the disclosure statement that accompanies the study:
Dr. Schneider has been a consultant for Pfizer, Eli Lilly, Johnson & Johnson, AstraZeneca, and Bristol-Myers Squibb. Dr. Keefe has received research support from AstraZeneca, Eli Lilly, and NIMH and has served as a consultant, adviser, or speaker for Abbott, Acadia, BiolineRx, Bristol-Myers Squibb, Cephalon, Cortex, Dainippon Sumitomo Pharma, Eli Lilly, Johnson & Johnson, Lundbeck, Memory Pharmaceuticals, Merck, Orexigen, Organon, Pfizer, Sanofi/Aventis, Schering-Plough, Wyeth, and Xenoport. Dr. Sano has served as a consultant or adviser for Aventis, Bayer, Bristol-Myers Squibb, Eisai, Elan, Forest, Genentech, GlaxoSmithKline, Janssen, Martek, Medivation, Novartis, Ortho-McNeil, Pfizer, Takeda, United BioSource, and Voyager. Dr. Sultzer has received research funding or lecture honoraria from or served as a consultant to AstraZeneca, Eli Lilly, Forest, and Pfizer. Dr. Lyketsos has received research funding, lecture honoraria, or travel support from or served as a consultant or adviser to Adlyfe, Associated Jewish Federation of Baltimore, AstraZeneca, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Ortho-McNeil, Monitor, Novartis, NIMH, National Institute on Aging, Pfizer, Supernus, Takeda, and Wyeth. Dr. Tariot has received research support or consulting or educational fees from Abbott, AC Immune, Alzheimer’s Association, Arizona Department of Health Services, AstraZeneca, Avid, Baxter Healthcare, Eisai, Elan, Epix, Forest, GlaxoSmithKline, Institute for Mental Health Research, Lundbeck, Memory, Merck, Merz, Mitsubishi Pharma, Myriad, National Institute on Aging, Neurochem, NIMH, Ono, Pfizer, Sanofi-Aventis, Takeda, and Wyeth; he is also a contributor to the patent “Biomarkers of Alzheimer’s Disease.” Dr. Stroup has received speaking or consulting fees from Eli Lilly, Janssen, and Lundbeck. The other authors report no financial relationships with commercial interests.
That’s quite the list. But granted, there were 13 researchers for this study and only 7 of them noted the above conflicts.
Can atypical antipsychotic medications be used in Alzheimer’s disease to help address aggressive behaviors? Yes, I believe they can — but not as a primary method of treatment, because they come with a lot of other problems when used in older populations. It’s my opinion that they should only be used when other methods have been tried unsuccessfully and the behavior has become extreme enough to warrant it.
Vigen et al. (2011). Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer’s Disease: Outcomes From CATIE-AD. The American Journal of Psychiatry, 1-9. doi: 10.1176/appi.ajp.2011.08121844