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Valproate in dementia: time to move on?: COMMENTARY ON… COCHRANE CORNER

  • Amreek Dhindsa (a1)

Baillon et al’s Cochrane review included 430 participants with agitation in dementia from five randomised controlled trials. Overall, the reviewers found that valproate was no better than placebo for the treatment of agitation in people with dementia; however, the quality of the studies included was very variable. Adverse effects and events were higher in the treatment group compared with the controls, although these finding were largely based on low-quality data with incomplete reporting; thus, valproate's safety profile is of concern. This review demonstrates that there is insufficient evidence to change current treatment guidelines.



Corresponding author
Correspondence Dr Amreek Dhindsa, Oxford University Hospitals NHS Foundation Trust, Paediatric Surgery, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Email:
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Baillon, SF, Narayana, U, Luxenberg, JS, et al. (2018) Valproate preparations for agitation in dementia. Cochrane Database of Systematic Reviews, 10: CD003945 (doi: 10.1002/14651858.CD003945.pub4).
Dekkers, OM, von Elm, E, Algra, A, et al. (2010) How to assess the external validity of therapeutic trials: a conceptual approach. International Journal of Epidemiology, 39: 8994.
Dolder, C, McKinsey, J (2010) Low-dose divalproex in agitated patients with Alzheimer's disease. Journal of Psychiatric Practice, 16: 63–7.
Dolder, C, Nealy, KL, McKinsey, J (2012) Valproic acid in dementia: does an optimal dose exist? Journal of Pharmacy Practice, 25: 142–50.
Forester, B, Vanelli, M, Hyde, J, et al. (2007) Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication American Journal of Geriatric Pharmacotherapy, 5: 209–17.
Higgins, JP, Green, S (eds) (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Cochrane Collaboration.
Ichikawa, J, Chung, YC, Dai, J, et al. (2005) Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release. Brain Research, 1052: 5662.
Ijaopo, EO (2017) Dementia-related agitation: a review of non-pharmacological interventions and analysis of risks and benefits of pharmacotherapy. Translational Psychiatry, 7(10): e1250.
Livingston, G, Barber, J, Marston, L, et al. (2017) Prevalence of and associations with agitation in residents with dementia living in care homes: MARQUE cross-sectional study. BJPsych Open, 3: 171–8.
Lonergan, E, Cameron, M, Luxenberg, J (2004) Valproic acid for agitation in dementia. Cochrane Database of Systematic Reviews, 2: CD003945 (doi: 10.1002/14651858.CD003945.pub2).
Lonergan, E, Luxenberg, J (2009) Valproate preparations for agitation in dementia. Cochrane Database of Systematic Reviews, 3: CD003945 (doi: 10.1002/14651858.CD003945.pub3).
Lott, AD, McElroy, SL, Keys, MA (1995) Valproate in the treatment of behavioral agitation in elderly patients with dementia. Journal of Neuropsychiatry and Clinical Neurosciences, 7: 314–9.
Meyer, RP, Schuyler, D (2015) Calming the agitated demented patient. Primary Care Companion for CNS Disorders, 17(1): doi 10.4088/PCC.15f01779.
Müller-Spahn, F (2003) Behavioral disturbances in dementia. Dialogues in Clinical Neuroscience, 5: 4959.
National Institute for Health and Care Excellence (2018a) Dementia: Assessment, Management and Support for People Living with Dementia and Their Carers (NICE Guideline NG97). NICE.
National Institute for Health and Care Excellence (2018b) Antipsychotics for Treating Agitation, Aggression and Distress in People Living with Dementia. Decision Aid: User Guide and Data Sources. NICE.
Panza, F, Solfrizzi, V, Imbimbo, B, et al. (2015) Alternative pharmacological treatment options for agitation in Alzheimer's disease. Geriatric Care, 1: 5460.
Porsteinsson, AP, Tariot, PN, Erb, R, et al. (2001) Placebo controlled study of divalproex sodium for agitation in dementia. American Journal of Geriatric Psychiatry, 9: 5866.
Roehr, B (2012) Abbott pays $1.6bn for promoting off label use of valproic acid. BMJ, 344: e3343.
Sival, RC, Haffmans, PM, Jansen, PA, et al. (2002) Sodium valproate in the treatment of aggressive behavior in patients with dementia – a randomised placebo controlled clinical trial. International Journal of Psychiatry, 17: 579–85.
Tariot, PN, Schneider, LS, Mintzer, JE, et al. (2001) Safety and tolerability of divalproex sodium in the treatment of signs and symptoms of mania in elderly patients with dementia: results of a double-blind, placebo-controlled trial. Current Therapeutic Research, 62: 5167.
Tariot, PN, Raman, R, Jakimovich, L, et al. (2005) Divalproex sodium in nursing home residents with possible or probable Alzheimer disease complicated by agitation: a randomized, controlled trial. American Geriatric Psychiatry, 13: 942–9.
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Valproate in dementia: time to move on?: COMMENTARY ON… COCHRANE CORNER

  • Amreek Dhindsa (a1)
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