title: A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer's disease.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mental Health and Neurodegeneration, Age Psychiatry, University of Manchester, Manchester, UK. Alistair.burns@manchester.ac.uk
authors.forename: Alistair
authors.initials: A
authors.lastname: Burns
authors.forename: Elaine
authors.initials: E
authors.lastname: Perry
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.forename: Paul
authors.initials: P
authors.lastname: Francis
authors.forename: Julie
authors.initials: J
authors.lastname: Morris
authors.forename: Melanie-Jayne R
authors.initials: MJ
authors.lastname: Howes
authors.forename: Paul
authors.initials: P
authors.lastname: Chazot
authors.forename: George
authors.initials: G
authors.lastname: Lees
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D019341:Aromatherapy / Q000009:adverse effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D031334:Melissa / Q000009:adverse effects / Q000737:chemistry*; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D010938:Plant Oils / Q000009:adverse effects / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000188:drug therapy / Q000523:psychology; D011788:Quality of Life; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D010938:Plant Oils; D000077265:Donepezil