Sodium valproate in aggressive behaviour in dementia: a twelve‐week open label follow‐up study

Sival, Rob C.; Duivenvoorden, Hugo J.; Jansen, Paul A. F.; Haffmans, P.M.J.; Duursma, S. A.; Eikelenboom, Piet

doi:10.1002/gps.1034

Cited by 23 publications

(14 citation statements)

References 31 publications

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“…It is possible that lower doses of valproate and a slower titration schedule may have improved tolerability. Similarly, longer treatment phases might be required to demonstrate benefit for valproate [23] . Regardless, the results of this study add to the mounting evidence of lack of efficacy and poor tolerability, and suggest that valproate should not be recommended as a first-line treatment for agitation and aggression in AD patients.…”

Section: Discussionmentioning

confidence: 99%

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

Herrmann

Lanctôt²,

Rothenburg³

et al. 2006

Dement Geriatr Cogn Disord

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Background/Aims: To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer’s disease (AD). Methods: This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering. Results: Fourteen patients (8 male/6 female) aged 85.6 ± 4.5 years with baseline Mini Mental State Examination scores of 4.5 ± 4.6 and NPI agitation/aggression scores of 6.4 ± 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = –2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = –2.82, p = 0.005). Conclusion: Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.

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Section: Discussionmentioning

confidence: 99%

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

Herrmann

Lanctôt²,

Rothenburg³

et al. 2006

Dement Geriatr Cogn Disord

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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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“…Except for reversible sedation in 8 patients and transient worsening of gait and confusion in 1 subject, no other side effects were observed. In an open-label extension trial of a double-blind study ongoing treatment with VPA (mean: 851 mg/d) was associated with improvement in measures of agitation in 46 patients [48]. Behavior was rated on the Social Dysfunction and Aggression Scale 9 (SDAS-9), a Dutch version of the Behavioral Observation Scales for Intrmural Psychogeriatrics (GIP), and the CGIC.…”

Section: Valproatementioning

confidence: 99%

“…Possible limitations of this study were the low dose of VPA and the relatively short treatment period. 39 patients were further examined in a twelve-week open label follow-up study [50]. Maintaining the same dosage of VPA aggressive, non-social, apathetic, disorientated behavior and distorted memory improved at week 12 compared to week 0.…”

Section: Valproatementioning

confidence: 99%

Anticonvulsants in the treatment of aggression in the demented elderly: an update

Amann

Pantel

Grunze

et al. 2009

Clinical Practice and Epidemiology in Mental Health

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IntroductionComplex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity.MethodsCommonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate.ResultsTo date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate.ConclusionSo far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.

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Sodium valproate in aggressive behaviour in dementia: a twelve‐week open label follow‐up study

Abstract: Low dose sodium valproate may be effective reducing a broad range of types of disturbed behaviours in aggressive demented patients. The high death rate underlines the fragility of demented patients with aggressive behaviour.

Cited by 23 publications

References 31 publications

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

Valproic Acid in Dementia

Anticonvulsants in the treatment of aggression in the demented elderly: an update

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