Combination Therapy in Alzheimer's Patients Significantly Eases Caregiver Distress

Pam Harrison

March 10, 2010

March 10, 2010 (Savannah, Georgia) — Caregiver distress is significantly attenuated when patients with moderate to severe Alzheimer’s disease (AD) are treated with a combination of extended-release memantine plus a cholinesterase inhibitor (ChEI) vs ChEI monotherapy, according to a multicenter, randomized, double-blind, placebo-controlled trial presented here at the American Association for Geriatric Psychiatry 2010 Annual Meeting.

George Grossberg, MD, St. Louis University, St. Louis, Missouri, and colleagues found a greater reduction in overall distress associated with behavioral disturbances as reflected by the total Neuropsychiatric Inventory–Caregiver Distress scale (NPI-D) at study endpoint among caregivers of patients treated with the combination strategy compared with caregivers of patients treated with ChEI monotherapy (P = .054 on last observed carried forward analysis [LOCF]).

Significant baseline–to–study endpoint benefits were also observed for individual NPI-D items, including agitation and aggression, irritability and lability, and nighttime behaviors, among caregivers of patients in the combination group compared with the monotherapy group.

Correlate of Early Nursing Home Admission

"The extent or amount of caregiver distress is the 1 factor that most closely correlates with early nursing home admission," Dr. Grossberg told Medscape Psychiatry. "So if we can ease stress on caregivers, we can enable them to keep patients at home longer, keep them out of the institutional setting longer, which is good for the patient’s quality of life and good financially."

A total of 335 patients with a diagnosis of probable AD who had been undergoing stable ChEI therapy for at least 3 months were randomized to extended-release memantine, 28 mg daily, and another 342 patients received placebo.

Roughly equal numbers of patients in both groups were taking donepezil, galantamine, or rivastigmine at baseline, and approximately 80% of each treatment group completed the 24-week trial. Memantine was titrated in 4 weekly increments of 7 mg each, reaching a target dose of 28 mg/day at the beginning of week 4.

Efficacy was assessed using the NPI-D scale, a 60-point tool given along with the NPI. Caregivers were asked to rate their distress associated with each NPI item on a scale of 0 (no distress) to 5 (extreme distress). The NPI assesses the frequency and severity of 12 behavioral symptoms in patients with dementia, with higher scores indicating greater impairment.

At week 24, the NPI-D total score in the combination group had decreased by a mean of 2.1 points (LOCF analysis) in the additional memantine group compared with a decrease of 1.2 points in the ChEI monotherapy group.

Individual items showing significant differences between groups at endpoint were agitation and aggression, irritability and lability, and nighttime behavior, all in favor of the additional extended-release memantine arm, investigators add.

"The instigating factor or trigger for institutionalization in AD patients is behavior — things like agitation, aggression, irritability, and nighttime behaviors. So when caregivers can’t sleep, they get exhausted," said Dr. Grossberg. "In this particular study, we were able to show statistically significant benefits in decreasing these problem behaviors with the combination approach, all potentially good outcomes for caregivers of AD patients."

Caregiver Distress Warrants Attention

Ellen Whyte, MD, University of Pittsburgh Medical Center, Pennsylvania, told Medscape Psychiatry that physicians use drugs to treat AD dementia primarily to slow cognitive impairment.

"However," she added, "there is evidence that both classes of medications improve behavior in AD patients as well, and I think this study nicely shows that both the stability of cognition and improvement in behavior lead to decreased stress in the caregiver."

"This is very important," she added, "physicians should worry about caregiver stress. When I’m working with families who have a patient with AD, I have to take care of the caregiver, because they are the lifeline. No matter what happens to the patient — whether they get institutionalized or stay at home — the caregiver is still very active and involved in the patient’s care, and we have to take care of them," said Dr. Whyte.

The study was supported by Forest Laboratories Inc. Dr. Grossberg reports that he has received research funding from Forest Laboratories Inc along with other pharmaceutical companies developing new treatments for AD. Dr. Whyte has disclosed no relevant financial relationships.

American Association for Geriatric Psychiatry (AAGP) 2010 Annual Meeting: Abstract NR 32. Presented March 6, 2010.

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