+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer's disease



A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer's disease



Dementia and Geriatric Cognitive Disorders 31(2): 158-164



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. 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. 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. 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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051129349

Download citation: RISBibTeXText

PMID: 21335973

DOI: 10.1159/000324438


Related references

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: A double blind, randomised, placebo controlled trial. Journal of Neurology Neurosurgery & Psychiatry 74(7): 863-866, 2003

The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group. Dementia 7(6): 293-303, 1996

Donepezil treatment of patients with severe Alzheimer's disease in a Japanese population: results from a 24-week, double-blind, placebo-controlled, randomized trial. Dementia and Geriatric Cognitive Disorders 25(5): 399-407, 2008

A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease. International Journal of Geriatric Psychiatry 26(9): 937-943, 2011

Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. Journal of Clinical Pharmacy and Therapeutics 28(1): 53-59, 2003

A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. PhytoTherapy Research 19(4): 335-340, 2005

The Efficacy and Safety of Donepezil in Patients with Alzheimer's Disease: Results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. Dementia and Geriatric Cognitive Disorders 7(6): 293-303, 1996

Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. Journal of Ethnopharmacology 164: 378-384, 2015

Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. American Journal of Geriatric Psychiatry 17(2): 166-169, 2009

Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Trial. Archives of Clinical Neuropsychology 34(3): 277-289, 2019

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. Journal of Clinical Psychiatry 63(7): 553-558, 2002

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology 50(1): 136-145, 1998

DHEA treatment of Alzheimer's disease: A randomized, double-blind, placebo-controlled trial. Neurology 62(6): 1030, 2004

Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. European Journal of Neurology 13(9): 981-985, 2006

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. International Journal of Geriatric Psychiatry 17(3): 270-278, 2002