Should Valproate (Depakote) Be Used to Treat Agitation in Alzheimer's?

In Alzheimer's Disease, Use Caution in Treating Agitation with Valproate
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What Is Valproate?

Valproate is a drug that is classified as an anticonvulsant medication and thus is typically prescribed to control seizures. It is also prescribed at times to prevent migraine headaches and to decrease manic episodes in bipolar disorder. Some physicians also prescribe it to treat the challenging behaviors in Alzheimer's disease and other types of dementia. Using valproate in this manner is considered off-label since it is not approved y the US Food and Drug Administration (FDA) for this use.

"Valproate products include valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics," according to the FDA. (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm192645.htm)

Valproate comes in different forms, including tablets, extended release tablets, capsules with valproate sprinkles (these capsules can be swallowed whole or opened and the contents sprinkled on soft food for those with difficulty swallowing) and injections/IVs for those who can't take oral medications.

Why Has Valproate Been Used to Treat Challenging Behaviors in Dementia?

One of the difficulties in Alzheimer's disease is that personalities and behaviors can change as a result of the disease. Some of the challenging behaviors in dementia can include agitation, restlessness, combativeness, verbal aggression, resistance to care, wandering and paranoid thinking.

It can be difficult to know how to respond to these types of behaviors and emotions.

The medical community has tried different drugs to try to reduce these behaviors, including antipsychotic medications (which can have significant negative side effects and are highly regulated in the nursing home industry), benzodiazepines (which also come with negative side effects and questionable effectiveness) and antidepressants (which aren't always effective or appropriate).

The bottom line is that there is generally not a highly effective medication to treat behavioral disturbances in dementia.

Thus, valproate rose as a contender in the attempt to treat agitation in dementia. In addition to the hope of it being an effective treatment, valproate had the advantage of being a medication that initially flew a little more under the radar in terms of the nursing home regulations- which are highly concentrated on the reduction and elimination of antipsychotic medications in dementia but not as focused on valproate.

Should Valproate Be Used to Treat Challenging Behaviors in Dementia?

According to multiple research studies, the answer generally is: No.

Why not?

It is often ineffective. Although there are isolated anecdotal cases of effectiveness, reviews of multiple studies concluded that valproate was not any more helpful than a placebo (fake pill) in decreasing the challenging behaviors of dementia.

According to another study published in JAMA Psychiatry, valproate also failed to slow down the cognitive progression of dementia, a hoped-for benefit that did not emerge with its use.

Side Effects

Multiple studies also found that the participants who received valproate were at a high risk for side effects from the medication. Those side effects included thrombocytopenia (decreased blood platelets), increased agitation, sedation and sleepiness, nausea, vomiting and diarrhea.

Alternatives to Valproate

Rather than reaching for the medication bottle to modify difficult behaviors in dementia, the first strategy should always be non-drug approaches. Consider factors that could be triggering those behaviors such as the environment, physical pain, discomfort or restlessness and try to address and adjust those potential causes.

Employ strategies such as allowing the person some time to calm down alone and then returning later to finish the task you're trying to accomplish.

Finally, recognize that caregiver stress and burnout can exacerbate the behaviors of someone with dementia. Monitor yourself for signs of caregiver overload and use family, friends and community resources to support you in your caregiver role.

Additional Resources

Sources:

ClinicalTrials.gov. Valproate in Dementia (VALID). July 6, 2010. http://clinicaltrials.gov/ct2/show/results/NCT00071721?sect=X64015#outcome1

The Cochrane Database of Systematic Reviews. 2009 Jul 8;(3).Valproate preparations for agitation in dementia. http://www.ncbi.nlm.nih.gov/pubmed/19588348

Depakote. Depakote Formulations. Accessed April 25, 2014. https://www.depakote.com/what-is-depakote

JAMA Psychiatry. Chronic Divalproex Sodium to Attenuate Agitation and Clinical Progression of Alzheimer Disease. http://archpsyc.jamanetwork.com/article.aspx?articleid=1107419

Mental Health Clinician. 2012;1(11):14. Dosing of Valproate in an Elderly Population With Dementia: Evaluation of Discontinuations and Dose Reductions. http://cpnp.org/resource/mhc/2012/05/dosing-valproate-elderly-population-dementia-evaluation-discontinuations-and

US Food and Drug Administration. Valproate Information. Accessed April 25, 2014. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm192645.htm

Williams, L. All Worked Up About the Evidence: Valproate for Agitation in Dementia.

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