Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease

Trinh, Nhi-Ha; Hoblyn, Jennifer; Mohanty, Subhanjoy; Yaffe, Kristine

doi:10.1001/jama.289.2.210

Cited by 464 publications

(276 citation statements)

References 50 publications

Supporting

Mentioning

241

Contrasting

Unclassified

Order By: Relevance

“…To our knowledge, this is the first NMA of ChEIs treatment in patients with AD in which compared using both direct and indirect comparisons of interventions across trials simultaneously. This should strengthen the findings from our analysis over previous meta‐analyses (Trinh et al , 2003; Birks, 2006; Hansen et al , 2008; Lockhart et al , 2011;Tan et al , 2014; Wang et al , 2014). The study quality of head‐to‐head trials might be questionable, because two out of three head‐to‐head trials were not double‐blinded.…”

Section: Resultssupporting

confidence: 89%

“…Previous meta‐analyses have consistently demonstrated that ChEIs have beneficial effects on neuropsychiatric symptoms (Trinh et al , 2003; Hansen et al , 2008; Lockhart et al , 2011; Tan et al , 2014; Wang et al , 2014). However, differences in efficacy between each ChEI were inconsistent.…”

Section: Resultsmentioning

confidence: 99%

“…To date, several reviews and meta‐analyses have been published summarising the efficacy and safety of second‐generation ChEIs for treatment of AD (Trinh et al , 2003; Birks, 2006; Hansen et al , 2008; Tan et al , 2014; Wang et al , 2014). However, comparative evidence is still sparse.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild‐to‐moderate Alzheimer's disease: a Bayesian network meta‐analysis

Kobayashi¹,

Ohnishi²,

Nakagawa³

et al. 2015

Int J Geriat Psychiatry

View full text Add to dashboard Cite

BackgroundComparative evidence for efficacy and safety of second‐generation cholinesterase inhibitors (ChEIs) is still sparse.ObjectivesThe purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild‐to‐moderate Alzheimer's disease (AD).MethodsWe conducted a systematic review for published articles and included randomised, double‐blind, placebo‐controlled trials and head‐to‐head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS‐Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview‐Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta‐analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions.ResultsAmong the 21 trials included, network meta‐analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS‐Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety.ConclusionsOur analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild‐to‐moderate AD.

show abstract

Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild‐to‐moderate Alzheimer's disease: a Bayesian network meta‐analysis

Kobayashi¹,

Ohnishi²,

Nakagawa³

et al. 2015

Int J Geriat Psychiatry

View full text Add to dashboard Cite

show abstract

“…Overall, these trials yielded, at best, mixed results regarding therapeutic efficacy and tolerability. Cholinesterase inhibitors and memantine have been reported to have small-to-medium effect size effects on neuropsychiatric symptoms, including psychosis and agitation; however, these data were obtained from secondary outcome measures and post hoc analyses of patients who often did not have clinically significant behavioral symptoms at baseline, and yet other trials have shown no effect of cognitive enhancers on behavior (Cummings et al, 2006a, b;Sink et al, 2005;McKeith et al, 2000;Trinh et al, 2003;Hermann et al, 2005). A prospective trial of donepezil for neuropsychiatric symptoms in outpatients with mildmoderate AD showed improvement in global neuropsychiatric symptoms during open-label treatment for 3 months, followed by symptomatic worsening only in placebo-treated patients during the subsequent randomized discontinuation phase of the trial (Holmes et al, 2004).…”

Section: Other Psychotropicsmentioning

confidence: 99%

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Jeste

Blazer

Casey

et al. 2007

Neuropsychopharmacol

Self Cite

325

273

View full text Add to dashboard Cite

In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6-1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/ or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.

show abstract

“…31 A recent meta-analysis of clinical studies assessing neuropsychiatric outcomes with the NPI in patients with mild to moderate AD reported modest benefits of the ChE inhibitors tacrine, donepezil, galantamine, and metrifonate for behavioral symptoms. 40 However, interpretation of these results is limited by the low incidence of behavioral problems and the use of psychoactive medications in this patient cohort. Nonetheless, in light of the modest benefits observed, it was proposed that ChE inhibitors be considered for the management of the neuropsychiatric symptoms in AD.…”

Section: Cholinesterase Inhibitors and Behavioral Symptoms Of Alzheimmentioning

confidence: 79%

Role of Cholinesterase Inhibitors in Managing Behavioral Problems in Alzheimer's Disease

Masterman¹

2004

Prim. Care Companion CNS Disord.

View full text Add to dashboard Cite

Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease

Cited by 464 publications

References 50 publications

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild‐to‐moderate Alzheimer's disease: a Bayesian network meta‐analysis

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild‐to‐moderate Alzheimer's disease: a Bayesian network meta‐analysis

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Role of Cholinesterase Inhibitors in Managing Behavioral Problems in Alzheimer's Disease

Contact Info

Product

Resources

About