Comparative efficacy and safety of therapy for the behavioral and psychological symptoms of dementia: a systemic review and Bayesian network meta-analysis

Jin, Boru; Liu, Huayan

doi:10.1007/s00415-019-09200-8

Cited by 37 publications

(44 citation statements)

References 33 publications

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“…Similar to two published NMAs of pharmacologic interventions in persons with dementia, we found that antipsychotics were associated with an increased risk of cerebrovascular events [30,31]. Although one of these NMAs included cholinesterase inhibitors, authors did not conduct analyses to assess for an association with mortality risk [30]. We found a possible association between cholinesterase inhibitor use and lower mortality risk among RCTs only; however, wide predictive intervals (that cross one) associated with this effect estimate suggest that, in a future study, we might not see this association.…”

Section: Discussionsupporting

confidence: 86%

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Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis

et al. 2020

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Background: Prescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia. Methods: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network metaanalyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 69%

Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis

et al. 2020

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“…Dementia is a neurodegenerative brain disorder with diverse clinical symptoms including cognitive impairment (e.g., memory loss and learning deficits) and non-cognitive disorders (e.g., behavioral and psychological deficits). Nearly 50 million patients worldwide develop dementia and this population is expected to exceed 130 million in 2050 (Prince et al, 2015; Jin and Liu, 2019). The global cost associated with dementia was about 1,000 billion dollars in 2015, and this continues to increase rapidly.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD): Management of Extrapyramidal Side Effects

2019

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Antipsychotic drugs are often used for the treatment of behavioral and psychological symptoms of dementia (BPSD), especially psychosis and behavioral disturbances (e.g., aggression and agitation). They are prescribed alone or in conjunction with anti-dementia (e.g., anti-Alzheimer’s disease drugs) and other psychotropic drugs (e.g., antidepressants). However, antipsychotic drugs frequently produce serious extrapyramidal side effects (EPS) including Parkinsonian symptoms (e.g., bradykinesia, akinesia, tremor, and muscle rigidity). Therefore, appropriate drug choice and combination strategy are important in the treatment of BPSD. Among anti-Alzheimer’s disease drugs, cholinesterase inhibitors (ChEIs, e.g., donepezil and galantamine) have a propensity to potentiate EPS associated with antipsychotic treatment in a synergistic manner. In contrast, the NMDA receptor antagonist memantine reduces antipsychotic-induced EPS. Antidepressant drugs, which inhibit 5-HT reuptake into the nerve terminals, also synergistically augment antipsychotic-induced EPS, while mirtazapine (α2, 5-HT2 and 5-HT3 antagonist) reduces the EPS induction. Importantly, previous studies showed that multiple 5-HT receptors play crucial roles in modulating EPS associated with antipsychotic treatment. Specifically, activation of 5-HT1A receptors or blockade of 5-HT2, 5-HT3 and 5-HT6 receptors can alleviate EPS induction both by antipsychotics alone and by combined antipsychotic treatments with ChEIs or 5-HT reuptake inhibitors. In this article, we review antipsychotic use in treating BPSD and discuss the favorable drug selection in terms of the management of antipsychotic-induced EPS.

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“…Beside cognitive functions, behavioral symptoms improved under treatment with AChE-I as well (Rolinski et al, 2012). Jin and Liu looked at the efficacy and safety of different drugs used to treat BPSD (Jin and Liu, 2019). They also found a positive effect for AChE-I.…”

Section: Bpsdmentioning

confidence: 99%

Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer’s Dementia Are Frequently Below the Recommended Levels

et al. 2020

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Background: Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration of the respective AChE-I. Objective: In patients with mild to moderate Alzheimer's dementia, we measured serum concentrations of hepatically metabolized donepezil and renally excreted rivastigmine and investigated possible modifiers. Additionally, we looked at correlations between serum concentrations and efficacy for both drugs. Methods: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatographytandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR). Allele specific PCR were performed to determine CYP2D6 genotype and gene dose. Clinical efficacy was assessed by changes of the subtest wordlist delayed recall of the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). Results: Sixty-seven patients treated with a stable dosage of donepezil 10 mg (n=41) or rivastigmine 9.5 mg (n=26) were included. Mean serum concentration of donepezil and rivastigmine were 41.2 and 6.5 ng/ml, respectively. Serum concentrations were below the recommended range in 73% of the subjects in the donepezil group and in 65% of the participants in the rivastigmine group. When applying a dose-related reference, ranges 63% of patients in the donepezil group and 32% in the rivastigmine group had concentrations below the expected range. Gene dose, sex, and duration of treatment significantly predicted donepezil serum concentration (p=0.046, p=0.001, p=0.030 respectively). Only for rivastigmine did the serum concentration significantly contribute

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Comparative efficacy and safety of therapy for the behavioral and psychological symptoms of dementia: a systemic review and Bayesian network meta-analysis

Cited by 37 publications

References 33 publications

Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis

Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis

Antipsychotic Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD): Management of Extrapyramidal Side Effects

Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer’s Dementia Are Frequently Below the Recommended Levels

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