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Effect of Divalproex Sodium on Behavioural and Cognitive Problems in Elderly Dementia

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Abstract

Background

Behavioural and psychological symptoms of dementia (BPSD) occur in up to 90% of individuals with dementia at some point in their illness. BPSD reduce patient quality of life, cause great distress to caregivers and are the most common reason for institutionalisation. In nursing homes, pharmacological measures (usually antipsychotics or benzodiazepines) are often required to control agitation and aggression in patients with dementia. However, no medications have been approved by the US Food and Drug Administration for this indication as yet. The antiepileptic agent divalproex sodium may have advantages in this setting because of lower rates of drug interactions and adverse effects in this patient population.

Objective

The aim of the study was to assess the impact of treatment with divalproex sodium on behavioural, mood and cognitive measures in a population of elderly nursing home residents with a history of behaviour problems associated with dementia.

Materials and methods

The study was a retrospective analysis of a long-term care database which allowed assessment of the impact of divalproex sodium therapy on behavioural, mood and cognitive measures in elderly nursing home residents with a history of dementia-related behaviour problems. Minimum Data Set items relating to problems of behaviour, cognition and mood were collected prior to and after divalproex sodium treatment over a 1-year period. Two-phase generalised linear regression, with fixed intersections at the time of divalproex sodium initiation, was used to estimate trends in each measure prior to and after divalproex sodium initiation. Monotherapy, combination therapy with benzodiazepines and antipsychotics, and dose comparisons of divalproex sodium were studied.

Results

In all three situations (i.e. as monotherapy, in combination with benzodiazepines and antipsychotics, and at both higher and lower doses), divalproex sodium therapy was shown to have multiple beneficial effects on various behavioural, mood and cognition indicators in elderly nursing home residents. In general, the data seemed to support more favourable results for the higher divalproex sodium dose group.

Conclusions

These data support the use of divalproex sodium in elderly nursing home residents with a history of dementia and behaviour problems and warrant conduct of prospective, randomised trials of the drug in this setting.

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References

  1. Bachman D, Weif P, Linn P. Prevalence of dementia and probably senile dementia of the Alzheimer type in the Framingham study. Neurology 1992; 42: 115–9

    Article  PubMed  CAS  Google Scholar 

  2. Lyketsos CG, Steinberg M, Tschanz JT, et al. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 2000; 157: 708–14

    Article  PubMed  CAS  Google Scholar 

  3. Tariot P. Treatment strategies for agitation and psychosis in dementia. J Clin Psychiatry 1996; 57: 21–9

    PubMed  CAS  Google Scholar 

  4. Dybicz S, Erwin WG, Helbers L, et al. Frequency and treatment patterns of behavioral symptoms in skilled nursing facility residents [abstract]. American Society of Consultant Pharmacists 33rd Annual Meeting, poster presentation 2002; 2002 Nov 13–16; Anaheim (CA)

  5. Tariot PN, Ismail MS. Use of quetiapine in elderly patients. J Clin Psychiatry 2002; 63Suppl. 13: 21–6

    PubMed  CAS  Google Scholar 

  6. Katz IR, Jeste DV, Mintzer JE, et al. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. J Clin Psychiatry 1999; 60: 107–15

    Article  PubMed  CAS  Google Scholar 

  7. Brodaty H, Ames D, Snowdon J, et al. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003; 54: 134–43

    Article  Google Scholar 

  8. De Deyn PP, Rabheru K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999; 53: 946–55

    Article  PubMed  Google Scholar 

  9. Street JS, Clark WS, Gannon KS, et al. Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in patients with Alzheimer’s dementia. Arch Gen Psychiatry 2000; 57: 968–76

    Article  PubMed  CAS  Google Scholar 

  10. FDA. FDA Public Health Advisory [online]. Available from URL: http://www.fda.gov/cder/drug/advisory/antipsychotics [Accessed 2005 Apr 4]

  11. Frenchman IB, Capo C, Kass H. Effect of treatment with divalproex sodium and lorazepam in residents of long-term-care facilities with dementia-related anxiety or agitation: retrospective chart review. Curr Ther Res 2000; 61: 621–9

    Article  CAS  Google Scholar 

  12. Tariot PN. Treatment of agitation in dementia. J Clin Psychiatry 1999; 60: 11–20

    Article  PubMed  Google Scholar 

  13. Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry 1998; 155: 54–61

    PubMed  CAS  Google Scholar 

  14. Tariot PN, Schneider LS, Mintzer JE. 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. Curr Ther Res Clin Exp 2001; 62: 51–67

    Article  CAS  Google Scholar 

  15. Porsteinsson AP, Tariot PN, Erb R, et al. An open trial of valproate for agitation in geriatric neuropsychiatric disorders. Am J Geriatr Psychiatry 1997; 5: 344–51

    Article  PubMed  CAS  Google Scholar 

  16. Porsteinsson AP, Tariot PN, Jakimovich LJ, et al. Valproate therapy for agitation in dementia: open-label extension of a double-blind trial. Am J Geriatr Psychiatry 2003; 11: 434–40

    PubMed  Google Scholar 

  17. Porsteinsson AP, Tariot PN, Erb R, et al. Placebo-controlled study of divalproex sodium for agitation in dementia. Am J Geriatr Psychiatry 2001; 9: 58–66

    PubMed  CAS  Google Scholar 

  18. Grossman F. A review of anticonvulsants in treating agitated demented elderly patients. Pharmacotherapy 1998; 18: 600–6

    PubMed  CAS  Google Scholar 

  19. Alexopoulos GS, Silver JM, Kahn DA, et al. The expert consensus guideline series: treatment of agitation in older persons with dementia. Postgrad Med 1998; 103(s-4): 1–88

    Google Scholar 

  20. Mellow AM, Solano-Lopez C, Davis S. Sodium valproate in the treatment of behavioral disturbance in dementia. J Geriatr Psychiatry Neurol 1993; 6: 205–9

    PubMed  CAS  Google Scholar 

  21. Goldberg RJ. The use of adjunctive divalproex for neuroleptic unresponsive behavioral disturbances in nursing home residents with dementia. Ann Long Term Care 1999; 7: 63–6

    Google Scholar 

  22. Tariot PN, Loy R, Ryan JM, et al. Mood stabilizers in Alzheimer’s disease: symptomatic and neuroprotective rationales. Adv Drug Deliv Rev 2002; 54: 1567–77

    Article  PubMed  CAS  Google Scholar 

  23. Manji HK, Moore GJ, Chen G. Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic depressive illness. Biol Psychiatry 2000; 48: 740–54

    Article  PubMed  CAS  Google Scholar 

  24. Chen G, Zeng WZ, Yuan PX, et al. The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CANS. J Neurochem 1999; 72: 879–82

    Article  PubMed  CAS  Google Scholar 

  25. Loy R, Tariot PN. Neuroprotective properties of valproate: potential benefit for AD and tauopathies. J Mol Neurosci 2002; 19: 303–7

    Article  PubMed  CAS  Google Scholar 

  26. Frederiksen K, Tariot P, DeJonghe E. Minimum Data Set Plus (MDS+) scores compared with scores from five rating scales. J Am Geriatr Soc 1996; 44: 305–9

    PubMed  CAS  Google Scholar 

  27. Morris JN, Jones RN, Fries BE, et al. Convergent validity of minimum data set-based performance quality indicators in postacute care settings. Am J Med Qual 2004; 19: 242–7

    Article  PubMed  Google Scholar 

  28. Sandborn W, Bendfeldt F, Hamdy R. Valproic acid for physically aggressive behavioral in geriatric patients. Am J Geriatr Psychiatry 1995; 3: 239–42

    Article  Google Scholar 

  29. Gupta S, O’Connell R, Parekh A, et al. Efficacy of valproate for agitation and aggression in dementia: case reports. Int J Geriatr Psychopharm 1998; 1: 244–8

    Google Scholar 

  30. Sival RC, Haffmans PM, van Gent PP, et al. The effects of sodium valproate on disturbed behavioral in dementia. J Am Geriatr Soc 1994; 42(8): 906–7

    PubMed  CAS  Google Scholar 

  31. Narayan M, Nelson JC. Treatment of dementia with behavioral disturbance using divalproex or a combination of divalproex and a neuroleptic. J Clin Psychiatry 1997; 58: 351–4

    Article  PubMed  CAS  Google Scholar 

  32. Kunik ME, Puryear L, Orengo CA, et al. The efficacy and tolerability of divalproex sodium in elderly demented patients with behavioral disturbances. Int J Geriatr Psychiatry 1998; 13: 29–34

    Article  PubMed  CAS  Google Scholar 

  33. Lott A, McElroy SL, Keys MA. Valproate in the treatment of behavioral agitation in elderly patients with dementia. J Neuropsychiatry Clin Neurosci 1995; 7: 314–9

    PubMed  CAS  Google Scholar 

  34. Haas S, Vincent K, Holt J, et al. Divalproex: a possible treatment alternative for demented, elderly aggressive patients. Ann Clin Psychiatry 1997; 9(3): 145–7

    PubMed  CAS  Google Scholar 

  35. Kasckow JW, McElroy SL, Cameron RL, et al. A pilot study on the use of divalproex sodium in the treatment of behavioral agitation in elderly patients with dementia: assessment with the Behave-AD and CGI rating scales. Curr Ther Res 1997; 58: 981–9

    Article  CAS  Google Scholar 

  36. Herrmann N. Valproic acid treatment of agitation in dementia. Can J Psychiatry 1998; 43: 69–72

    PubMed  CAS  Google Scholar 

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Acknowledgements

Funding from Abbott Laboratories, Abbott Park, IL, USA was provided for this project.

The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Neuroscience, Abbott Laboratories, Abbott Park, Illinois, USA

    Jane M. Meinhold (Neuroscience Research Scientist)

  2. Northwestern University Medical School, Chicago, Illinois, USA

    Lesley M. Blake

  3. The University of Chicago Department of Psychiatry, Chicago, Illinois, USA

    Louis J. Mini

  4. Department of Biostatistics and Psychiatry, University of Cincinnati, Cincinnati, Ohio, USA

    Jeffrey A. Welge & Michael Schwiers

  5. Beverly Enterprises, Fort Smith, Arkansas, USA

    Anthony Hughes

Authors
  1. Jane M. Meinhold
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  2. Lesley M. Blake
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  3. Louis J. Mini
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  4. Jeffrey A. Welge
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  5. Michael Schwiers
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  6. Anthony Hughes
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Correspondence to Jane M. Meinhold.

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Meinhold, J.M., Blake, L.M., Mini, L.J. et al. Effect of Divalproex Sodium on Behavioural and Cognitive Problems in Elderly Dementia. Drugs Aging 22, 615–626 (2005). https://doi.org/10.2165/00002512-200522070-00007

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