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Vol. 31, No. 2, 2011
Issue release date: March 2011

A Double-Blind Placebo-Controlled Randomized Trial of Melissa officinalis Oil and Donepezil for the Treatment of Agitation in Alzheimer’s Disease

Burns A. · Perry E. · Holmes C. · Francis P. · Morris J. · Howes M.-J.R. · Chazot P. · Lees G. · Ballard C.
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Abstract

Background/Aims: Behavioural and psychological symptoms (BPSD) are frequent in people with Alzheimer’s disease and cause considerable stress to patients and their carers. Antipsychotics have been widely used as a first-line treatment, resulting in an estimated 1,800 excess strokes and 1,600 excess deaths in the UK alone. Safe and effective alternatives are urgently needed. Based upon preliminary evidence from clinical trials, aromatherapy with melissa oil may be such an alternative, but initial studies have been modest in size, and adequate blinding has been problematic. Our objective was to assess the efficacy of melissa aromatherapy in the treatment of agitation in people with Alzheimer’s disease in an adequately powered and robustly blinded randomized controlled trial comparing it with donepezil, an anticholinesterase drug used with some benefit to treat BPSD. Methods and Findings: The study was a double-blind parallel-group placebo-controlled randomized trial across 3 specialist old age psychiatry centres in England. Participants had probable or possible Alzheimer’s disease, were resident in a care home, had clinically significant agitation (defined as a score of 39 or above on the Cohen Mansfield Agitation Inventory) and were free of antipsychotics and/or anticholinesterase for at least 2 weeks. Participants were allocated to 1 of 3 groups: placebo medication and active aromatherapy; active medication and placebo aromatherapy or placebo of both. Main Outcome: The primary outcome measure was reduction in agitation as assessed by the Pittsburgh Agitation Scale (PAS) at 4 weeks. This is an observational scale, and raters were required to wear nose clips to ensure that full blinding was maintained. The PAS, Neuropsychiatric Inventory (NPI; another measure of BPSD) and other outcome measures were completed at baseline, 4-week and 12-week follow-ups. 114 participants were randomized, of whom 94 completed the week 4 assessment and 81 completed the week 12 assessment. Aromatherapy and donepezil were well tolerated. There were no significant differences between aromatherapy, donepezil and placebo at week 4 and week 12, but importantly there were substantial improvements in all 3 groups with an 18% improvement in the PAS and a 37% improvement in the NPI over 12 weeks. Conclusion: When assessed using a rigorous design which ensures blinding of treatment arms, there is no evidence that melissa aromatherapy is superior to placebo or donepezil, in the treatment of agitation in people with Alzheimer’s disease. However, the sizeable improvement in the placebo group emphasizes the potential non-specific benefits of touch and interaction in the treatment of agitation in people with Alzheimer’s disease.



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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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References

  1. Alzheimer’s Society: Dementia UK 2007. London, Alzheimer’s Society, 2007. http://alzheimers.org.uk/site/scripts/download_info.php?fileID=1.
  2. Alzheimer’s Research Trust: Dementia 2010. Oxford, Health Economics Research Centre, 2010.
  3. Burns A, Robert P: The national dementia strategy in England. BMJ 2009;338:931.

    External Resources

  4. Ballard C, et al: Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol 2009;5:245–255.
  5. Ballard C, Howard R: Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci 2006;7:492–500.
  6. FDA Public Health Advisory: Deaths with antipsychotics in elderly patients with behavioral disturbances. 2005. http://www.fda.gov/Cder/drug/advisory/antipsychotics.htm.
  7. FDA Public Health Advisory: Deaths with antipsychotics in elderly patients with behavioral disturbances. 2008. www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm053171.htm.
  8. NICE/SCIE: Dementia: supporting people with dementia and their carers in health and social care. http://www.nice.org.uk/Guidance/CG42 (accessed 10/03/2009), 2006.
  9. Chenoweth L, et al: Caring for Aged Dementia Care Resident Study (CADRES) of person-centred care, dementia-care mapping, and usual care in dementia: a cluster-randomised trial. Lancet Neurol 2009;8:317–325 (erratum published in Lancet Neurol 2009;8:419).
  10. Fossey J, et al: Effect of enhanced psychosocial care on antipsychotic use in nursing home residents with severe dementia: cluster randomised trial. BMJ 2006;332:756–761.
  11. Loy C, Schneider L: Galantamine for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev 2006;1:CD001747.
  12. Trinh NH, et al: Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA 2003;289:210–216.
  13. Holmes C, et al: Risperidone and rivastigmine and agitated behaviour in severe Alzheimer’s disease: a randomised double blind placebo controlled study. Int J Geriatr Psychiatry 2007;22:380–381.
  14. Howard R, et al: Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med 2007;357:1382–1392.
  15. Burns A, et al: Bright light therapy for agitation in dementia: a randomised controlled trial. Int Psychogeriatr 2009;21:711–721.
  16. Burns A, et al: Sensory stimulation in dementia: an effective option for managing behavioural problems. Br Med J 2002;325:1312–1313.
  17. MacMahon S, Kermode S: A clinical trial of the effects of aromatherapy on motivational behaviour in a dementia care setting using a single subject design. Aust J Holist Nurs 1998;52:47–49.
  18. Wolfe N, Herzberg J: Can aromatherapy oils promote sleep in severely demented patients? Int J Geriatr Psychiatry 1996;11:926–927.

    External Resources

  19. Brooker D, et al: Single case evaluation of the effects of aromatherapy and massage on disturbed behaviour in severe dementia. Br J Clin Psychol 1997;1:287–296.
  20. Holt FE, et al: Aroma therapy for dementia.Cochrane Datab Syst Rev 2003;3:CD003150. DOI: 10.1002/14651858.CD003150.

    External Resources

  21. Ballard C, et al: Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind placebo-controlled trial with melissa. J Clin Psychiatry 2002;63:553–558.
  22. Abuhamdah S, et al: Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channels. J Pharm Pharmacol 2008;60:377–384.
  23. Elliott M, et al: The essential oils from Melissa officinalis L. and Lavandulaangustifolia Mill. as potential treatment for agitation in people with severe dementia. Int J Essent Oil Ther 2007;1:143–152.
  24. Huang LP, et al: Pharmacological profile of essential oils derived from Lavandulaangustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels. J Pharm Pharmacol 2008;60:1515–1522.
  25. Lee L, et al: Melissa aromatherapy as safe and effective treatment. Nurs Resident Care 2003;5:80–82.
  26. Cohen-Mansfield J, Marx M, Rosenthal A: A description of agitation in a nursing home. J Gerontol Med Sci 1989;44:77–84.
  27. McKhann G, et al: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services task force on Alzheimer’s disease. Neurology 1984;34:939–944.
  28. Hughes C, et al: A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566–572.
  29. Cummings JL: Alzheimer’s disease. N Engl J Med 2004;351:56–67.
  30. Rosen J, et al: The Pittsburg Agitation Scale: a user friendly instrument for rating agitation in dementia patients. Am J Geriatr Psychiatry 1994;2:52–59.

    External Resources

  31. Mahoney F, Barthel D: Functional evaluation: the Barthel Index. Md State Med J 1965;14:56–61.

    External Resources

  32. Cummings JL, et al: The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.
  33. Blau T: Quality of life, social indicators, and criteria of change. Prof Psychol 1977;8:464–473.
  34. Katz I, et al: Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group. J Clin Psychiatry 1999;60:107–115.
  35. Ballard C, et al: Quetiapine and rivastigmine and cognitive decline in Alzheimer’s disease: randomised double blind placebo controlled trial. BMJ 2005;330:874.


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