The Spectrum of Behavioral Responses to Cholinesterase Inhibitor Therapy in Alzheimer Disease

Mega, Michael S.; Masterman, Donna; O’Connor, Susan; Barclay, Terry R.; Cummings, Jeffrey L.

doi:10.1001/archneur.56.11.1388

Cited by 226 publications

(139 citation statements)

References 18 publications

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“…Hecker [18] reported improvement with donepezil in depression, anxiety, and apathy areas of the NPI when compared with placebo over 4 and 24 weeks in 191 moderate-severe AD patients. In a retrospective study in 86 AD patients Mega et al [19] observed significant improvement from baseline in delusions, agitation, anxiety, disinhibition, and irritability in responders to donepezil. The behavioral changes were dose-dependent.…”

Section: Donepezilmentioning

confidence: 98%

Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents

Burt

2000

Curr Psychiatry Rep

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Section: Donepezilmentioning

confidence: 98%

Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents

Burt

2000

Curr Psychiatry Rep

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“…The study sample size was estimated based on a clinically relevant difference of 4 points on NPI, 29,30 a SD of 12 points, 31,32 and an estimated correlation with baseline of 0.6 and interclass correlation coefficient of 0.6. Approximately 130 patients were required for a power of 80% (2-sided testing at 0.05).…”

mentioning

confidence: 99%

Tetrahydrocannabinol for neuropsychiatric symptoms in dementia

et al. 2015

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Objective: To study the efficacy and safety of low-dose oral tetrahydrocannabinol (THC) in the treatment of dementia-related neuropsychiatric symptoms (NPS).Methods: This is a randomized, double-blind, placebo-controlled study. Patients with dementia and clinically relevant NPS were randomly assigned to receive THC 1.5 mg or matched placebo (1:1) 3 times daily for 3 weeks. Primary outcome was change in Neuropsychiatric Inventory (NPI), assessed at baseline and after 14 and 21 days. Analyses were based on intention-to-treat.Results: Twenty-four patients received THC and 26 received placebo. NPS were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant (mean difference NPI total : 3.2, 95% confidence interval [CI] 23.6 to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation Inventory 4.6, 95% CI 23.0 to 12.2), quality of life (Quality of Life-Alzheimer's Disease 20.5, 95% CI 22.6 to 1.6), or activities of daily living (Barthel Index 0.6, 95% CI 20.8 to 1.9). The number of patients experiencing mild or moderate adverse events was similar (THC, n 5 16; placebo, n 5 14, p 5 0.36). No effects on vital signs, weight, or episodic memory were observed.Conclusions: Oral THC of 4.5 mg daily showed no benefit in NPS, but was well-tolerated, which adds valuable knowledge to the scarce evidence on THC in dementia. The benign adverse event profile of this dosage allows study of whether higher doses are efficacious and equally welltolerated. Classification of evidence:This study provides Class I evidence that for patients with dementiarelated NPS, low-dose THC does not significantly reduce NPS at 21 days, though it is welltolerated. Neurology ® 2015;84:2338-2346 GLOSSARY AD 5 Alzheimer disease; AE 5 adverse event; CCGIC 5 Caregiver Clinical Global Impression of Change; CI 5 confidence interval; CMAI 5 Cohen-Mansfield Agitation Inventory; NPI 5 Neuropsychiatric Inventory; NPS 5 neuropsychiatric symptoms; PAL WMS-R 5 Paired Associate Learning Wechsler Memory Scale-Revised; QoL-AD 5 Quality of Life-Alzheimer's Disease Scale; RCT 5 randomized controlled trial; THC 5 D-9-tetrahydrocannabinol.

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“…In several open-label studies, donepezil treated AD patients demonstrated improvements on a variety of behavioral measures and specific behaviors such as delusions, agitation, anxiety, aggression and disinhibition. 182,183 Donepezil may also provide significant benefit for patients with LBD, especially for behaviors such as hallucinations, agitation and apathy, though certain side effects such as worsening of parkinsonism and sedation may be more common than in patients with AD. 184,185 Finally, in a large randomized placebo-controlled trial of the cholinesterase inhibitor metrifonate for mild to moderate AD, total behavioral scores improved with a significant improvement in hallucinations.…”

Section: Cholinergic Medicationsmentioning

confidence: 99%

Recommendations for the Management of Behavioral and Psychological Symptoms of Dementia

Herrmann

2001

Can. J. Neurol. Sci.

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Suppl. 1 -S96 serious problem that they encountered, rating it more frequently as a serious problem than the memory disturbance itself. The significance of BPSD was recently endorsed by both the United States A l z h e i m e r's A s s o c i a t i o n 6 and the International Psychogeriatric Association 1 as research priorities. The phenomenology and prevalence of BPSD have beenThe behavioral and psychological symptoms of dementia (BPSD) include delusions, hallucinations, misidentifications, agitation, wandering, pacing, restlessness, disinhibition, apathy, negativism, emotional lability, depression, anxiety, sleep disturbance and sexually inappropriate behaviours.1 While not included as diagnostic criteria for dementia by DSM-IV 2 or the NINCDS-ADRDA, 3 behaviours such as paranoia, depression, euphoria and apathy were recognized by Alzheimer in the initial description of the illness that bears his name. 4 Historically, the focus on BPSD began only recently, prompted by an early study by Rabins et al,5 who interviewed caregivers of patients with dementia. While these behaviours were noted in 50-90% of patients, caregivers considered physical aggression the most ABSTRACT: Background: The behavioral and psychological symptoms of dementia (BPSD) are common, serious problems that impair the quality of life for both patient and caregiver. In order to provide recommendations based upon the best available evidence, a qualitative literature review was performed. Methods: A search of the English language medical literature published between 1966 and 2000 was performed. The quality of the studies was assessed by considering the subjects, trial design, analysis and results. Final recommendations were based upon the quality of available evidence. Results: The management of BPSD begins with a thorough assessment to search for underlying causes of behaviour change. Concomitant medical illness should be treated and sensory impairment ameliorated. Nonpharmacological approaches should be instituted prior to medication use. These interventions include music, light, changes in level of stimulation and specific behavioral techniques. Antipsychotics are the best studied pharmacological intervention for agitation and aggression and have demonstrated modest but consistent efficacy. Antidepressants such as trazodone and selective serotonin re-uptake inhibitors, as well as anticonvulsants such as carbamazepine and valproic acid have also demonstrated efficacy. Benzodiazepines can be used for short-term treatment as p.r.n. agents when necessary. Pharmacotherapy must be monitored closely for both effectiveness and side effects, with consideration of medication withdrawal when appropriate. Conclusion: The management of BPSD can significantly improve the quality of life for the patient and caregiver. Their assessment and management are essential components of the treatment of dementia.RÉSUMÉ: Recommandations pour la prise en charge des symptômes comportementaux et psychologiques de la démence. Introduction: L e s symptômes comportementaux et ...

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The Spectrum of Behavioral Responses to Cholinesterase Inhibitor Therapy in Alzheimer Disease

Abstract: Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.

Cited by 226 publications

References 18 publications

Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents

Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents

Tetrahydrocannabinol for neuropsychiatric symptoms in dementia

Recommendations for the Management of Behavioral and Psychological Symptoms of Dementia

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