Donepezil for the Treatment of Behavioral Symptoms in Patients With Alzheimer's Disease

Abstract

Behavioral and psychologic symptoms of dementia (BPSD) are common manifestations in mid- and late-stage Alzheimer's disease (AD). Traditional treatments for BPSD are neuroleptics and sedatives, which are not devoid of serious adverse effects. A number of studies show beneficial effects in the treatment of BPSD with acetylcholinesterase inhibitors (AChEI). The present study aimed to evaluate the effect of donepezil (using the generic drug Memorit) as monotherapy for AD patients suffering from BPSD. Twenty-eight consecutive patients followed at the Memory Outpatient Clinic and Psychogeriatric Department of the Abarbanel Mental Health Center were treated with donepezil for 6 months. Starting dose was 5 mg daily during the first 4 weeks and continuation with 10 mg daily thereafter. Treatment effects were evaluated using the Mini Mental State Examination (MMSE), the Neuro-Psychiatric Inventory (NPI), and the Clinical Global Impression of Change Scale (CGIC) caregiver version. Twenty-four of 28 patients completed the study. Of these, five patients needed additional rescue neuroleptic treatment due to incomplete response. The mean dose of donepezil was 9.10 mg/day (median 10 mg/day). The overall NPI improved significantly from 33.4 to 21.2 (p = 0.008). The mean CGIC at study's end was 3.0 (mild improvement). The cognitive scores did not change significantly. When compared to the patients who completed the study, patients who discontinued had higher mean scores on the irritability and agitation subscales of the NPI, they were older, and they had longer disease duration and lower MMSE mean scores. Three adverse events were recorded: one syncope causing a toe phalanx fracture and gastrointestinal complaints that resolved over time in two additional patients. Acetylcholinesterase inhibitors should be considered for the treatment of BPSD before neuroleptic treatment is instituted in AD patients with low levels of irritability and agitation.

Cholinergic–serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease

“…This cholinergic dysfunction in AD has been largely related to cognitive disturbances (Francis, Palmer, Snape, & Wilcock, 1999;Perry, Walker, Grace, & Perry, 1999). Besides cognitive symptoms, most patients with AD suffer from be-independent from effects on cognition, in patients with AD (Paleacu, Mazeh, Mirecki, Even, & Barak, 2002) may have important clinical implications. However, it is conceivable that, due to the complexity and diversity of BPSD, more than one transmitter system may contribute to a particular behavioral syndrome; indeed, balance between pairs of neurotransmitters may be of particular importance, e.g.…”

Pharmacologic Management of Agitation in Alzheimer’s Disease

“…A secondary analysis of behavioral data from a 6-month, placebo-controlled trial of donepezil in nursing home residents with probable AD complicated by behavioral symptoms showed some evidence for reduced agitation [97]. In a case series, 28 patients with AD treated with donepezil 5 mg/day for 1 month followed by a mean dose of 10 mg/day for 5 months showed improvement in symptoms of agitation [98].…”

Preventing falls in In-Patient Older Adult Mental Health Services: Different Causative Factors in Mental and Neurocognitive Disorders

“…Medication with strongest links to an increased risk of falling includes serotonin reuptake inhibitors and tricyclic antidepressants [39], antipsychotic agents [40], benzodiazepines and anticonvulsants [25]. Many medications can cause side effects such as hypotension/orthostatic hypotension, extrapyramidal effects, slowed reactions, and symptoms like dizziness, syncope, and weakness, which increases the risk for falls by affecting gait, balance and mobility [41]. They may also cause sedation and sensory disturbances that alter perception [42] and level or alertness and anticholinergic effects that may contribute to risk of falls by increasing the need for ambulation to meet toileting needs [43].…”