Valproate for agitation in critically ill patients: A retrospective study

Gagnon, David J.; Fontaine, G; Smith, Kathryn; Riker, Richard R.; Miller, Russell R.; Lerwick, Patricia; Lucas, F. Lee; Dziodzio, John; Sihler, Kristen C.; Fraser, Gilles L.

doi:10.1016/j.jcrc.2016.09.006

Cited by 59 publications

(92 citation statements)

References 40 publications

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“…Our data highlight the potential benefit of monitoring free serum valproate concentrations in critically ill patients, and increase the reported cases in the ICU literature nearly 5‐fold. This finding is important because valproate is a preferred agent for seizure control and an emerging option for the management of ICU agitation . One report suggests that valproate may be more effective (75%) than phenytoin (59%) or levetiracetam (52%) to control status epilepticus .…”

Section: Discussionmentioning

confidence: 99%

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

et al. 2017

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“…Agitation in DLB often needs to be managed with low doses of atypical antipsychotic drugs [38, 47], but the dose may be limited due to motor side effects. Recent studies have shown that low doses of valproic acid (or divalproex) can be used as an adjunct to drugs like quetiapine in managing the agitation of DLB [49, 50, 52, 53]. Pimavanserin is approved by the FDA for treating psychosis in PD, but it also needs to be tested in DLB patients who are experiencing hallucinations and delusions [41].…”

Section: Resultsmentioning

confidence: 99%

“…A systematic review performed by the Cochrane Database demonstrated that valproic acid (or divalproex) does not appear to be as useful for managing agitation in dementia patients when it is prescribed as monotherapy [51]. Nevertheless, more recent studies have demonstrated that valproic acid is effective as adjunctive therapy for agitation and delirium [52, 53]. Both of these studies showed that by using valproic acid in acutely agitated patients, doses of opioids and other concomitant psychoactive medications could be reduced.…”

Section: Treatments For Fluctuations and Agitation In Dlbmentioning

confidence: 99%

Pharmacological Management of Dementia with Lewy Bodies

Hershey

Coleman-Jackson

2019

Drugs Aging

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Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer’s disease and Parkinson’s disease (PD). The median age of onset for DLB (76.3 years) is younger than that seen in PD dementia (81.4 years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer’s changes in their brains, explaining the wide variability in this disease’s clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent (E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.

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“…A subsequent report of valproate for ICU behavioral control was published in 2017 . This multicenter retrospective cohort study included 53 critically ill adults who received valproate for agitation.…”

Section: Valproatementioning

confidence: 99%

“…Enteral formulations can be used when patients are stabilized on the intravenous formulation and can be accomplished by using a 1:1 conversion. Valproate was likely titrated to clinical effect in the largest study to date . Evaluation of valproate serum concentration is reasonable in certain circumstances: the pharmacokinetics of the drug are difficult to predict (e.g., obesity, drug‐drug interactions, compromised liver function, impaired absorption) when a question arises about the safety of increasing the dose in a patient who is not responding to standard doses or when toxicity is suspected.…”

Section: Valproatementioning

confidence: 99%

Repurposing Valproate, Enteral Clonidine, and Phenobarbital for Comfort in Adult ICU Patients: A Literature Review with Practical Considerations

et al. 2017

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Provision of adequate sedation is a fundamental part of caring for critically ill patients. Propofol, dexmedetomidine, and benzodiazepines are the most commonly administered sedative medications for adult patients in the intensive care unit (ICU). These agents are limited by adverse effects, need for a monitored environment for safe administration, and lack of universal effectiveness. Increased interest has recently been expressed about repurposing older pharmacologic agents for patient comfort in the ICU. Valproate, enteral clonidine, and phenobarbital are three agents with increasing evidence supporting their use. Potential benefits associated with their utilization are cost minimization and safe administration after transition out of the ICU. This literature review describes the historical context, pharmacologic characteristics, supportive data, and practical considerations associated with the administration of these agents for comfort in critically ill adult patients.

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Valproate for agitation in critically ill patients: A retrospective study

Cited by 59 publications

References 40 publications

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

Pharmacological Management of Dementia with Lewy Bodies

Repurposing Valproate, Enteral Clonidine, and Phenobarbital for Comfort in Adult ICU Patients: A Literature Review with Practical Considerations

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