Valproate Therapy for Agitation in Dementia: Open-Label Extension of a Double-Blind Trial

Porsteinsson, Anton P.; Tariot, Pierre N.; Jakimovich, Laura; Kowalski, Nancy; Holt, Connie; Erb, Rosemary; Cox, Christopher

doi:10.1097/00019442-200307000-00006

Cited by 38 publications

(10 citation statements)

References 18 publications

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“…Uncontrolled open trials, case reports or case series have suggested the efficacy of VPA for variant BPSD [19–26], although RCTs showed conflicting results. Five RCTs [27–31] looking at the effect of VPA monotherapy on BPSD are listed in Table 2.…”

Section: Valproate (Vpa)mentioning

confidence: 99%

Mood stabilizers for the treatment of behavioral and psychological symptoms of dementia: An update review

Yeh

Ouyang

2012

The Kaohsiung J of Med Scie

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Behavioral and psychological symptoms of dementia (BPSD) are common and debilitating problems, but current treatments are limited. Antipsychotic agents show some efficacy on BPSD, but their use is limited by the associated risk of cerebrovascular events and mortality. Reports have shown the efficacy of mood stabilizers on BPSD, but systemic reviews on this issue are scant. This article aims to review studies of the efficacy of mood stabilizers on BPSD, and the quality of the available evidence. We searched for articles published in English during the period 1990 to 2010 and included in the PubMed database that concerned treatment of BPSD with mood stabilizers, such as carbamazepine, valproate, gabapentin, topiramate, lamotrigine, oxcarbazepine and lithium. The quality of the studies was assessed by considering the trial designs, analyses, subjects and results. We found one meta-analysis and three randomized controlled trials (RCTs) supporting the efficacy of carbamazepine in managing global BPSD, particularly aggression and hostility. With regard to valproate, current evidence from one meta-analysis and five RCTs did not strongly support its efficacy for global BPSD, including agitation and aggression. Only open trials or case series showed some efficacy of gabapentin, topiramate and lamotrigine in controlling BPSD. The single RCT investigating the effect of oxcarbazepine on agitation and aggression showed negative results. Case series reports on lithium tended to show it to be ineffective. Thus far, among mood stabilizers, carbamazepine has the most robust evidence of efficacy on BPSD. More RCTs are needed to strengthen evidence regarding the efficacy of gabapentin, topiramate and lamotrigine. Valproate, oxcarbazepine and lithium showed low or no evidence of efficacy. Large and well designed RCTs focusing on specific symptoms of BPSD are needed to deal with the issue.

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Section: Valproate (Vpa)mentioning

confidence: 99%

Mood stabilizers for the treatment of behavioral and psychological symptoms of dementia: An update review

Yeh

Ouyang

2012

The Kaohsiung J of Med Scie

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“…An initial study showed efficacy in treating aggressive behaviors and agitation [20] . However, this was not replicated in a subsequent double-blind, placebocontrolled study [21] .…”

Section: Mood Stabilizersmentioning

confidence: 99%

Pharmacological management of behavioral symptoms associated with dementia

Madhusoodanan

Ting

2014

WJP

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Core tip: Dementia may present with neuropsychiatric symptoms that may require pharmacological interventions. Medications used for the behavioral symptoms associ ated with dementia are not Food and Drug Administration approved and hence are being used offlabel in the United States. The decision to start medications is based on a judi cious consideration of risks and benefits. The choice of the agent should be guided by a thorough understanding of its pharmacologic properties and safety profiles, concomitant medications, and concurrent medical conditions. This article reviews the current evidence for psychotropic medications and presents recommendations with an algorithm for the treatment of neuropsychiatric symptoms associated with dementia. INTRODUCTIONDementia is a clinical syndrome which includes a heterogeneous group of disorders that lead to cognitive decline in the absence of delirium [1] . Although the cognitive decline is a core feature of dementia, this may be associated with a variety of neuropsychiatric symptoms [1] . These symptoms are as follows: (1) affective and motivational symptoms; (2) perceptual disturbances; (3) delusions; (4) disturbances of basic drives; and (5) disinhibition and inappropriate behaviors [1] . A five-year study on the AbstractDementia is a clinical syndrome with features of neurocognitive decline. Subtypes of dementia include Alzheimer's, frontotemporal, Parkinson's, Lewy body disease, and vascular type. Dementia is associated with a variety of neuropsychiatric symptoms that may include agitation, psychosis, depression, and apathy. These symptoms can lead to dangerousness to self or others and are the main source for caregiver burnout. Treatment of these symptoms consists of nonpharmacological and pharmacological interventions. However, there are no Food and Drug Administrationapproved medications for the treatment of behavioral and psychological symptoms of dementia. Pharmacological interventions are used offlabel. This article reviews the current evidence supporting or negating the use of psychotropic medications along with safety concerns, monitoring, regulations, and recommendations. REVIEWSubmit a

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“…, 1995; Kasckow et al. , 1997; Narayan and Nelson, 1997; Porsteinsson et al. , 1997; 2001; 2003; Herrmann, 1998; Kunik et al.…”

Section: Admentioning

confidence: 99%

Pharmacology of epigenetics in brain disorders

Narayan

Dragunow

2010

British J Pharmacology

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Epigenetics is a rapidly growing field and holds great promise for a range of human diseases, including brain disorders such as Rett syndrome, anxiety and depressive disorders, schizophrenia, Alzheimer disease and Huntington disease. This review is concerned with the pharmacology of epigenetics to treat disorders of the epigenome whether induced developmentally or manifested/acquired later in life. In particular, we will focus on brain disorders and their treatment by drugs that modify the epigenome. While the use of DNA methyl transferase inhibitors and histone deacetylase inhibitors in in vitro and in vivo models have demonstrated improvements in disease-related deficits, clinical trials in humans have been less promising. We will address recent advances in our understanding of the complexity of the epigenome with its many molecular players, and discuss evidence for a compromised epigenome in the context of an ageing or diseased brain. We will also draw on examples of species differences that may exist between humans and model systems, emphasizing the need for more robust pre-clinical testing. Finally, we will discuss fundamental issues to be considered in study design when targeting the epigenome.

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Valproate Therapy for Agitation in Dementia: Open-Label Extension of a Double-Blind Trial

Cited by 38 publications

References 18 publications

Mood stabilizers for the treatment of behavioral and psychological symptoms of dementia: An update review

Mood stabilizers for the treatment of behavioral and psychological symptoms of dementia: An update review

Pharmacological management of behavioral symptoms associated with dementia

Pharmacology of epigenetics in brain disorders

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