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Original Research Article

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

Herrmann N.a, b, d, e · Lanctôt K.L.a-d · Rothenburg L.S.a, b · Eryavec G.d-f

Author affiliations

aNeuropharmacology Research Program and bDepartment of Psychiatry, Sunnybrook Health Sciences Centre, and Departments of cPharmacology, dPsychiatry and eMedicine, University of Toronto, Toronto, and fSeniors’ Health Centre, North York General Hospital, North York, Canada

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Dement Geriatr Cogn Disord 2007;23:116–119

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Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Received: June 21, 2006
Accepted: December 09, 2006
Published online: December 04, 2006
Issue release date: January 2007

Number of Print Pages: 4
Number of Figures: 1
Number of Tables: 1

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: https://www.karger.com/DEM

Abstract

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.

© 2007 S. Karger AG, Basel


References

  1. Finkel S: Introduction to behavioural and psychological symptoms of dementia (BPSD). Int J Geriatr Psychiatry 2000;15(suppl 1):S2–S4.
    External Resources
  2. Marx MS, Cohen-Mansfield J, Werner P: Agitation and falls in institutionalized elderly persons. J Appl Gerontol 1990;9:106–117.
  3. Evans LK, Strumpf NE: Tying down the elderly. A review of the literature on physical restraint. J Am Geriatr Soc 1989;37:65–74.
  4. Lopez OL, Wisniewski SR, Becker JT, Boller F, DeKosky ST: Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Arch Neurol 1999;56:1266–1272.
  5. Moritz DJ, Fox PJ, Luscombe FA, Kraemer HC: Neurological and psychiatric predictors of mortality in patients with Alzheimer disease in California. Arch Neurol 1997;54:878–885.
  6. Keene J, Hope T, Fairburn CG, Jacoby R, Gedling K, Ware CJ: Natural history of aggressive behaviour in dementia. Int J Geriatr Psychiatry 1999;14:541–548.
  7. Herrmann N, Lanctôt KL, Sambrook R, Lesnikova N, Hebert R, McCracken P, Robillard A, Nguyen E: The contribution of neuropsychiatric symptoms to the cost of dementia care. Int J Geriatr Psychiatry 2006;21:972–976.
  8. Herrmann N, Lanctôt KL: Do atypical antipsychotics cause stroke? CNS Drugs 2005;19:91–103.
  9. Schneider LS, Dagerman KS, Insel P: Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934–1943.
  10. Herrmann N: Recommendations for the management of behavioral and psychological symptoms of dementia. Can J Neurol Sci 2001;28(suppl 1):S96–S107.
  11. Tariot PN, Schneider LS, Mintzer JE, Cutler AJ: Safety and tolerability of divalproex sodium in treatment of signs and symptoms of mania in elderly patients with dementia: results of a double-blind placebo-controlled trial. Curr Ther Res Clin Exp 2001;62:51–67.
  12. Porsteinsson AP, Tariot PN, Erb R, Cox C, Smith E, Jakimovich L, Noviasky J, Kowalski N, Holt CJ, Irvine C: Placebo-controlled study of divalproex sodium for agitation in dementia. Am J Geriatr Psychiatry 2001;9:58–66.
  13. Sival RC, Haffmans PM, Jansen PA, Duursma SA, Eikelenboom P: Sodium valproate in the treatment of aggressive behavior in patients with dementia – A randomized placebo controlled clinical trial. Int J Geriatr Psychiatry 2002;17:579–585.
  14. Lonergan ET, Cameron M, Luxenberg J: Valproic acid for agitation in dementia. Cochrane Database Syst Rev 2004;2:CD003945.
  15. Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  16. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J: The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.
  17. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L: Cerebral blood flow in dementia. Arch Neurol 1975;32:632–637.
  18. Cohen-Mansfield J, Billig N: Agitated behaviors in the elderly. 1. A conceptual review. J Am Geriatr Soc 1986;34:711–721.
  19. Tariot PN, Raman R, Jakimovich L, Schneider L, Porsteinsson A, Thomas R, Mintzer J, Brenner R, Schafer K, Thal L: Divalproex sodium in nursing home residents with possible or probable Alzheimer disease complicated by agitation: a randomized, controlled trial. Am J Geriatr Psychiatry 2005;13:942–949.
  20. Lanctôt KL, Herrmann N, Rothenburg L, Eryavec GM: Behavioral correlates of GABAergic disruption in Alzheimer’s disease. Int Psychogeriatr 2006, published online.
  21. Lanctôt KL, Herrmann N, Mazzotta P, Khan LR, Ingber N: GABAergic function in Alzheimer’s disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia. Can J Psychiatry 2004;49:439–453.
    External Resources
  22. Trannel TJ, Ahmed I, Goebert D: Occurrence of thrombocytopenia in psychiatric patients taking valproate. Am J Psychiatry 2001;158:128–130.
  23. Sival RC, Duivenvoorden HJ, Jansen PA, Haffmans PM, Duursma SA, Eikelenboom P: Sodium valproate in aggressive behaviour in dementia: a twelve-week open label follow-up study. Int J Geriatr Psychiatry 2004;19:305–312.

Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Received: June 21, 2006
Accepted: December 09, 2006
Published online: December 04, 2006
Issue release date: January 2007

Number of Print Pages: 4
Number of Figures: 1
Number of Tables: 1

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: https://www.karger.com/DEM


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