Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication

Forester, Brent P.; Vanelli, Mark; Hyde, Joan; Perez, Rosa Janeth Gomez; Ahokpossi, Calixte; Sribney, William M.; Adkison, Lesley

doi:10.1016/j.amjopharm.2007.09.001

Cited by 30 publications

(19 citation statements)

References 10 publications

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“…22 Anticonvulsant mood stabilizers are used for agitation and aggression in particular, although trials evaluating their efficacy and safety for frail elderly are scant, and results are mixed. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Some anticonvulsants, such as valproate and carbamazepine, carry US Food and Drug Administration (FDA) boxed warnings because of hepatic and bone marrow toxicities. 38,39 Antipsychotic medications have the best evidence for improving BPSD, although they work only 25% to 30% of the time.…”

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confidence: 99%

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia

Kerns

Winter

et al. 2018

J Am Board Fam Med

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Background: Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD.Methods: Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primarycare practice for at least 3 years in Northwestern Virginia.Results: PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management.Conclusions: PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development. (J Am Board Fam Med 2018;31: 9 -21.)

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confidence: 99%

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia

Kerns

Winter

et al. 2018

J Am Board Fam Med

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“…Eighteen of the studies examined the effects of valproic acid on patients with psychosis or behavioral disturbances in dementia, [33][34][35][36][39][40][41][42][43][44][45][46][47][48][49][50][51][52] one investigation involved valproic acid for the prevention of behaviors, 53 and another trial investigated the tolerability of valproic acid. 54 Seventeen of the 20 investigations administered divalproex, the remaining 3 trials employed sodium valproate.…”

Section: Review Componentmentioning

confidence: 99%

Valproic Acid in Dementia

Dolder

Nealy

McKinsey

2011

Journal of Pharmacy Practice

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Valproic acid is widely used in the treatment of behavioral disturbances in patients with dementia; however, there is uncertainty about its dosing and studies have reported mixed findings. The current article examines published trials of valproic acid in the treatment of patients with dementia to identify whether an optimal dosing strategy exists. Secondarily, valproic acid dosing from published studies is compared with a real-world 5-year sample of valproic acid prescribing. Twenty studies met selection criteria and were included in the review. Based primarily on uncontrolled trials and the current retrospective study, valproic acid serum levels between 40 and 60 mcg/mL and relatively low doses (ie, 7-12 mg/kg per d) are associated with improvements in agitation in some patients with dementia. At the same time, similar valproic acid levels produced no significant behavioral improvements in most placebo-controlled studies and led to substantial side effects in some patients. Considerable trial design differences exist between controlled and uncontrolled trials. Overall, valproic acid appears to have limited efficacy as monotherapy in many patients with dementia. Its optimal role may be in combination with other psychotropics as a treatment of agitation associated with dementia.

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“…The potential of drugs that interfere with DNMT activity may go beyond these examples of synaptic and behavioral plasticity. In mice, for example, treatment with DNMT inhibitors can confer stroke protection after mild ischemia; furthermore, haploinsufficiency for Dnmt1 in mice is associated with smaller infarction volumes after acute ischemia and stroke [36, 37]. For neurological diseases, the few DNA methylation markers that have been identified so far require further validation in large-scale multicenter studies.…”

Section: Potential Targets For Epigenetic Therapeutic Interventionsmentioning

confidence: 99%

“…A recent clinical trial revealed significant worsening of agitation and aggression in AD patients receiving VPA versus placebo [35]. Moreover, the effectiveness of VPA in treating behavioral symptoms in elderly dementia patients with agitation and aggressive behaviors has also been limited; low doses of VPA fail to reduce agitation in all patients, and high doses in some patients lead to unacceptable adverse effects [36, 37]. While HDAC inhibition may have limited benefits in AD patients and dementia, alternative methods of manipulating the general DNA hypomethylation seen in AD may hold greater therapeutic promise.…”

Section: Implications For Treatment In Neurodegenerative Disordersmentioning

confidence: 99%

Epigenetics-Based Therapeutics for Neurodegenerative Disorders

Jin

2012

Curr Tran Geriatr Gerontol Rep

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Epigenetic regulation, such as DNA methylation and histone modification, is implicated in the aberrant changes in gene expression that occur during the progression of neurodegeneration. Many epigenetics-based drugs have been developed recently for the treatment of some neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s diseases. Here we review recent studies that highlight the role of epigenetic modifications in neurodegeneration, among them DNA methylation and demethylation and histone acetylation and deacetylation; we also explore the possibility of using epigenetics-based therapeutics to treat neurodegenerative disorders.

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Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication

Cited by 30 publications

References 10 publications

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia

Valproic Acid in Dementia

Epigenetics-Based Therapeutics for Neurodegenerative Disorders

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