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The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer's Disease.

ABSTRACT: According to the World Alzheimer's report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer's disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer's disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and non-pharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents.

SUBMITTER: Calsolaro V

PROVIDER: S-EPMC6915160 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer's Disease.

Calsolaro Valeria V Antognoli Rachele R Okoye Chukwuma C Monzani Fabio F

Frontiers in pharmacology 20191206

According to the World Alzheimer's report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer's disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer's disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the pr ...[more]

PMID: 31920655

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Project description:BackgroundAlzheimer's disease (AD) is the most prevalent form of dementia and represents one of the highest unmet requirements in medicine today. There is shortage of novel molecules entering into market because of poor pharmacokinetic properties and safety issues. Drug repurposing offers an opportunity to reinvigorate the slowing drug discovery process by finding new uses for existing drugs. The major advantage of the drug repurposing approach is that the safety issues are already investigated in the clinical trials and the drugs are commercially available in the marketplace. As this approach provides an effective solution to hasten the process of providing new alternative drugs for AD, the current study shows the molecular interaction of already known antipsychotic drugs with the different protein targets implicated in AD using in silico studies.ResultA computational method based on ligand-protein interaction was adopted in present study to explore potential antipsychotic drugs for the treatment of AD. The screening of approximately 150 antipsychotic drugs was performed on five major protein targets (AChE, BuChE, BACE 1, MAO and NMDA) by molecular docking. In this study, for each protein target, the best drug was identified on the basis of dock score and glide energy. The top hits were then compared with the already known inhibitor of the respective proteins. Some of the drugs showed relatively better docking score and binding energies as compared to the already known inhibitors of the respective targets. Molecular descriptors like molecular weight, number of hydrogen bond donors, acceptors, predicted octanol/water partition coefficient and percentage human oral absorption were also analysed to determine the in silico ADME properties of these drugs and all were found in the acceptable range and follows Lipinski's rule.ConclusionThe present study have led to unravel the potential of leading antipsychotic drugs such as pimozide, bromperidol, melperone, anisoperidone, benperidol and anisopirol against multiple targets associated with AD. Benperidol was found to be the best candidate drug interacting with different target proteins involved in AD.

Project description:BACKGROUND:Certain Chinese medicine (CM) herbs and acupuncture may protect against Alzheimer's disease (AD). However, there is a lack of research regarding the use of CM in patients with AD. The aim of this study was to investigate CM usage patterns in patients with AD, and identify the Chinese herbal formulae most commonly used for AD. METHODS:This retrospective, nationwide, population-based cohort study was conducted using a randomly sampled cohort of one million patients, selected from the National Health Insurance Research Database between 1997 and 2008 in Taiwan. CM use and the top ten most frequently prescribed formulae for treating AD were assessed, including average formulae dose and frequency of prescriptions. Demographic characteristics, including sex, age and insurance level were examined, together with geographic location. Existing medical conditions with the behavioral and psychological symptoms of dementia, and medications associated with CM were also examined. Factors associated with CM use were analyzed by multiple logistic regressions. RESULTS:The cohort included 1137 newly diagnosed AD patients, who were given conventional treatment for AD between 1997 and 2008. Among them, 78.2 % also used CM treatments, including Chinese herbal remedies, acupuncture and massage manipulation. Female patients (aOR 1.57 with 95 % CI 1.16-2.13) and those living in urban areas (aOR 3.00 with 95 % CI 1.83-4.90 in the middle of Taiwan) were more likely to use CM. After adjusting for demographic factors, AD patients suffering from the behavioral and psychological symptoms of dementia were more likely to seek CM treatment than those with no symptoms (aOR 2.26 with 95 % CI 1.48-3.43 in patients suffering more than three symptoms). Bu-Zhong-Yi-Qi-Tang and Ji-Sheng-Shen-Qi-Wan were the two formulae most frequently prescribed by CM practitioners for treating AD. CONCLUSION:Most people with AD who consumed herbal products used supplement qi, nourish the blood, and quiet the heart spirit therapy as complementary medicines to relieve AD-related symptoms, in addition to using standard anti-AD treatments.

Project description:Behavioral and psychological symptoms of dementia are symptoms of disturbed perception, mood, behavior, and thought content that occurred frequently. These symptoms, which include apathy, depression, anxiety, psychosis, agitation, and aggression, can serve as predictors of and early clinical diagnostic markers for Alzheimer's disease (AD) and are common precipitants of institutional care. Agitation and psychosis are associated with accelerated disease progression and increased tau phosphorylation in patients with AD. Current guidelines recommend the use of second-generation antipsychotics for the treatment of agitation and psychosis in AD, but only after first-line non-pharmacological interventions and for no longer than 12 weeks because long-term use of these drugs is associated with an increased risk of mortality and an increased frequency of cerebrovascular events. Therefore, new antipsychotic drugs with improved efficacy and safety are needed as an alternative to current antipsychotic drugs. In this report, we discuss some of the most relevant advances in the field of agitation and psychosis in AD and focus on the recent positive clinical evidence observed with two new antipsychotics drugs: brexpiprazole and pimavanserin. Brexpiprazole is a receptor partial agonist (D2, D3, 5-HT1A), receptor antagonist (5-HT2A/B, α1B/α2C) according to the neuroscience-based nomenclature. Two recent phase III clinical trials have shown that brexpiprazole 2 mg/day is effective for the treatment of agitation in patients with AD and has an improved tolerability and safety profile compared with currently available second-generation antipsychotics. Pimavanserin is a receptor antagonist (5-HT2A, 5-HT2C) that has been given market authorization for psychosis occurring in Parkinson's disease. Recent phase II studies suggest that this drug is effective in AD patients with more severe psychosis, although further long-term studies are needed to better define the efficacy and long-term safety profile of pimavanserin for the treatment of psychosis in AD.

Dataset Information

The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer's Disease.

Publications

The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer's Disease.

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