The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary.
OBJECTIVE
New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998. While only 2 cholinesterase inhibitors, donepezil and tacrine, were available in 1998, 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants. However, there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments. We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia.


METHODS
Based on a literature review, a 61-question survey was developed with 1,225 options. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, the experts were asked to write in answers. The survey was sent to 50 North American experts on dementia, 100% of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. Based on the 95% confidence interval around the mean, we assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option. Guidelines indicating preferred treatment strategies were then developed for selected clinical situations.


RESULTS
For patients at risk for dementia, the experts recommended control of hypertension and diabetes. They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia. Cholinesterase inhibitors were an option for patients with mild cognitive impairment (i.e., at risk for Alzheimer's dementia [AD]). To slow cognitive impairment in mild/moderate AD, the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and galantamine were the preferred cholinesterase inhibitors. The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate (NMDA) antagonist (e.g., memantine) if a patient with mild/moderate dementia has an inadequate response to monotherapy. Control of hypertension and diabetes was the treatment of choice, in patients with mild/moderate vascular or mixed AD/vascular dementia, with aspirin another first-line option. Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia. Among nonpharmacological interventions for mild/moderate dementia, the experts recommended caregiver education, supportive therapy for caregivers, referral to day treatment, exercise programs, and respite care. For moderate/severe AD or mixed AD/vascular dementia, the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor. For moderate/severe vascular or mixed AD/vascular dementia, they recommended control of hypertension and diabetes. The experts' ratings underscore the importance of nonpharmacological strategies aimed at reducing caregiver burden in more severe dementia. Management of agitation and other behavioral disturbances was another focus of this study. The experts recommended using an atypical antipsychotic for agitation associated with delirium, psychosis, aggression, or anger. They would also consider divalproex to manage anger with a risk of physical aggression. Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia. Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety. Trazodone was recommended for insomnia. The experts also gave recommendations concerning dosage levels, duration of treatment, and choice of medications for patients with different complicating conditions.


CONCLUSIONS
The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances. Within the limits of expert opinion and with the expectation that new research data will take precedence, these guidelines may provide direction for clinicians offering care to patients with dementia.
Alexopoulos
George S
GS
Jeste
Dilip V
DV
Chung
Henry
H
Carpenter
Daniel
D
Ross
Ruth
R
Docherty
John P
JP
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003704:Dementia / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D015140:Dementia, Vascular / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy; D004359:Drug Therapy, Combination; D006801:Humans
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors