Uses of Intravenous Valproate in Geriatric Psychiatry

doi:10.1097/00019442-200108000-00017

The American Journal of Geriatric Psychiatry

Volume 9, Issue 3, Summer 2001, Pages 306-308

https://doi.org/10.1097/00019442-200108000-00017 Get rights and content

The authors describe the use of intravenous sodium valproate (Depacon®) to treat three geriatric inpatients: two acutely manic patients who refused oral medication and one dementia patient with agitation and dysphagia receiving end-of-life care for Alzheimer's disease.

Section snippets

Case 1

Mr. M., an 85-year-old widowed man with a 50-year history of bipolar disorder, was referred from his nursing home for involuntary admission to our Geropsychiatry Inpatient Unit for refusing to take medications, stating that as a priest, a doctor, and an undercover FBI agent, he knew they were poison. The apparent precipitant of this manic episode was the impending third anniversary of his wife's death. Medical history included Parkinson's disease, hypertension, congestive heart failure, and

Case 2

Ms. X., a 67-year-old divorced woman with a 30-year history of bipolar disorder, was involuntarily admitted to our Geropsychiatry Inpatient Unit after being brought to the emergency room by police for walking the streets in an open gown. This behavior was preceded by 2 weeks of insomnia, irritability, and threats to her children that began after stopping her valproate. Past medical history was remarkable for breast cancer, congestive heart failure, and lithium toxicity. Ms. X. was highly

Case 3

Mr. B., a 91-year-old widowed man with a 3-year history of Alzheimer's dementia, was referred from his assisted living facility for evaluation of increasing agitation over the past 2 weeks, involving flailing his limbs and hitting staff. He was also recently unable to take fluids, food, or medication by mouth because of difficulty swallowing. He had been prescribed donepezil, quetiapine, lorazepam, and zolpidem, to no avail. Medical history was remarkable for recent repeated hospitalizations

DISCUSSION

These three cases suggest that IV valproate administered without initial loading and in divided doses is well tolerated and may be an effective treatment for acute symptoms of mania and for dementia-related agitation in geriatric patients who are unwilling or unable to take oral medication. This is consistent with reports that oral valproate is well tolerated and effective in open-label trials in elderly patients with mania or dementia-related agitation.2., 10. Controlled clinical trials are

References (10)

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Safety of intravenous valproate
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There are more references available in the full text version of this article.

Cited by (18)

Intravenous valproate in the treatment of acute manic episode in bipolar disorder: A review
2020, Journal of Affective Disorders
Citation Excerpt :
Interestingly, IV valproate seems to be efficacious not only in adults but also in adolescents and elderly patients. Specifically, Regenold and Prasad (2001) explored the efficacy of IV valproate in 2 cases of BD-I manic patients, aged 85 and 67 years old respectively. In the first case, the administration of IV valproate up to 500 mg over the course of one day and then switched to oral valproate resulted in a good clinical response, despite the persistence of delusions.
Mania is a state of elated or irritable mood characterizing Bipolar Disorder type I (BD-I). Among the pharmacological treatments for the management of mania, mood stabilizers are regularly employed, with valproate being one of the most used because of its effectiveness. However, while the oral formulation is approved for acute mania, it is unclear whether the intravenous (IV) formulation could be a valid and safe alternative.
We performed a bibliographic research on PUBMED of all studies investigating the use of IV valproate as a treatment of acute mania in BD-I. A total of 13 studies met our inclusion criteria.
Overall, the results suggest that IV valproate as a loading therapy is an efficacious, safe and well tolerated treatment for manic episodes, and it is comparable to the oral loading regimen. Interestingly, only a few patients experienced significant side effects due to the administration of the IV valproate.
Few open label clinical trials have explored the effect of IV valproate in manic patients. Moreover, the original studies employed different clinical assessments and included manic patients taking other drugs, which made it impossible to determine whether the resolution of symptoms was due to valproate therapy alone. Additionally, serum valproate levels were not assessed by all studies.
IV valproate may represent a valid option for the management of acute mania, with comparable effects in terms of efficacy and safety to the oral valproate. However, larger and more homogeneous studies are warranted in order to collect more precise information on the beneficial effect of IV valproate.
Alternative formulations, delivery methods, and administration options for psychotropic medications in elderly patients with behavioral and psychological symptoms of dementia
2010, American Journal Geriatric Pharmacotherapy
Objective: The purpose of this paper was to review alternative formulations, delivery methods, and administration options for psychotropic medications in elderly patients with behavioral and psychological symptoms of dementia (BPSD).
Methods: A MEDLINE search was conducted initially in December 2008 and was updated in September 2009, including the search terms pharmacologic treatment and dementia, behavioral and psychological symptoms of dementia, alternative psychotropic medication formulations, alternative dosing methods of medication, drug delivery options, antidepressants and dementia, anxiolytics and dementia, antipsychotics and dementia, mood stabilizers and dementia, cognitive enhancers and dementia, medications and enteral feeding tubes, and hiding medication. Studies were limited to English-language articles dated from 1950 to 2009. Additional relevant articles were obtained by reviewing the references in the initial articles. Drug Facts and Comparisons 4.0 Online, Lexi-Comp Online, and Lexi-Drugs Online were used to obtain additional information. Targeted patients were elderly individuals with BPSD who were considered difficult to treat because they were unable to swallow, were refusing medications, or were not able to eat or drink per physician order.
Results: In addition to the standard capsule or tablet given orally, a variety of formulations and delivery methods for psychotropic medications are available. Options include short- and long-acting intramuscular, intravenous, liquid, orally disintegrating, transdermal patch, sublingual, and rectal forms. Additionally, all formulations can be further altered in substance, delivery, or both. For example, tablets may be crushed and capsules opened; this changes their formulation and allows the option of mixing with food or liquids to be taken by mouth or through a tube. Caution must be used, however; in certain cases, alteration of the original form or the intended delivery method is contraindicated. In addition, many alternative administration options are not formally approved for use in the manner in which they are commonly applied and are therefore used with little or no information on tolerability and effectiveness. Ethical and legal issues include patient consent and off-label use.
Conclusions: Overall, few studies have examined the use and efficacy of alternative psychotropic formulations and delivery methods in elderly patients with BPSD, and none have specifically addressed drug-alteration and alternative-administration issues. There is no evidence to compare alternative delivery forms (eg, tablet or capsule) of a given medication in terms of efficacy or tolerability. Still, alternative methods may be the only option for treatment of some patients. Practitioners must be familiar with the range of formulations and delivery options available so that they can optimize their patients' medication regimens. More data are needed on the use of alternative formulations, delivery methods, and administration options and their limitations in this population.
Evidence-based pharmacological treatment of geriatric bipolar disorder
2005, Psychiatric Clinics of North America
Pharmacotherapy of bipolar disorder in old age: Review and recommendations
2004, American Journal of Geriatric Psychiatry
Citation Excerpt :
There are no available data regarding the efficacy of atypical agents in elderly BP patients. Mixed-age patients benefit from using adjunctive risperidone with DVP and/or LI, but few patients over age 55 were included in these reports.34,35 Olanzapine monotherapy is superior to placebo in manic mixed-age patients.34,36
The authors reviewed the evidence-base for pharmacological treatment of mania and bipolar (BP) depression in late life. Treatment benefits and side effects may be modified by age-associated factors, such as neurocognitive impairments. Lithium and divalproex have most often been studied in elderly patients, and both may be efficacious in acute treatment of mania, but there are no controlled efficacy or effectiveness trials. The role of atypical antipsychotic agents remains to be clarified. Similarly, there are no systematic studies of the treatment of BP depression in elderly patients. The authors make suggestions for management and delineate priorities for research.
Solid Oral Dosage Forms Use in Adults with Neurological Disorders and Swallowing Difficulties: A Scoping Review
2022, Dysphagia
Effectiveness and safety of intravenous valproate in agitation: a systematic review
2022, Psychopharmacology

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: This work was supported by an unrestricted grant from Abbott Laboratories.

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Clinical and Research ReportUses of Intravenous Valproate in Geriatric Psychiatry

Section snippets

Case 1

Case 2

Case 3

DISCUSSION

Am J Geriatr Psychiatry

Psychiatr Clin North Am

Efficacy of divalproex vs. lithium and placebo in the treatment of mania. The Depakote Mania Study Group (published erratum appears in JAMA 1994; 271:1830; see comments)

JAMA

Safety of intravenous valproate

Ann Neurol

Clinical and Research Report
Uses of Intravenous Valproate in Geriatric Psychiatry