Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease: Clinical Evidence and Possible Mechanisms

Damiana Scuteri, Luigi Antonio Morrone, Laura Rombolà, Pina Rosa Avato, Anna Rita Bilia, Maria Tiziana Corasaniti, Shinobu Sakurada, Tsukasa Sakurada, Giacinto Bagetta, Damiana Scuteri, Luigi Antonio Morrone, Laura Rombolà, Pina Rosa Avato, Anna Rita Bilia, Maria Tiziana Corasaniti, Shinobu Sakurada, Tsukasa Sakurada, Giacinto Bagetta

Abstract

The treatment of agitation and aggression, typical Behavioural and Psychological Symptoms of Dementia (BPSDs) of Alzheimer's Disease (AD), is one of the most complicated aspects of handling patients suffering from dementia. Currently, the management of these symptoms often associated with an increased pain perception, which notably reduces the patients' quality of life (QoL), relies on the employment of antipsychotic drugs. Unfortunately, the use of these pharmacological agents has some limits: in the long term, they do not result in being equally effective as in the first weeks of treatment and they present important side effects. Therefore, there is growing interest, supported by clinical evidence, in aromatherapy for the control of agitation, aggression, and psychotic symptoms. Some molecular mechanisms have been proposed to explain the behavioural effects of essential oils, as the whole phytocomplex or the single components, but important basic research effort is still needed. For this reason, rigorous preclinical studies are necessary in order to understand the pharmacological basis of aromatherapy in the treatment of BPSDs and to widen the cluster of effective essential oils in pharmacotherapeutic practice.

Figures

Figure 1
Figure 1
PubMed search on essential oils. An exponential growth of scientific production about essential oils is displayed in the figure from the 80s to 2016.

References

    1. Alzheimer A., Stelzmann R. A., Schnitzlein H. N., Murtagh F. R. An English translation of Alzheimer's 1907 paper, ‘Uber eine eigenartige Erkankung der Hirnrinde’. Clinical Anatomy. 1995;8(6):429–431.
    1. Ballard C., Orrell M., Zhong S. Y., et al. Impact of antipsychotic review and nonpharmacological interventionon antipsychotic use, neuropsychiatric symptoms, and mortality in people with dementia living in nursing homes: a factorial cluster-randomized controlled trial by the well-being and health for people with dementia (WHELD) program. American Journal of Psychiatry. 2016;173(3):252–262. doi: 10.1176/appi.ajp.2015.15010130.
    1. Barage S. H., Sonawane K. D. Amyloid cascade hypothesis: pathogenesis and therapeutic strategies in Alzheimer's disease. Neuropeptides. 2015;52:1–18. doi: 10.1016/j.npep.2015.06.008.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) Washington, DC, USA: American Psychiatric Association; 1987.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th. Washington, DC, USA: American Psychiatric Association; 1994. ((DSM-IV)).
    1. Ballard C. G., Gauthier S., Cummings J. L., et al. Management of agitation and aggression associated with Alzheimer disease. Nature Reviews Neurology. 2009;5(5):245–255. doi: 10.1038/nrneurol.2009.39.
    1. Achterberg W., Pieper M. J., van Dalen-Kok A. H., et al. Pain management in patients with dementia. Clinical Interventions in Aging. 2013;8:1471–1482. doi: 10.2147/cia.s36739.
    1. Hardy J. A., Higgins G. A. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184–185. doi: 10.1126/science.1566067.
    1. Cummings J. L., Morstorf T., Zhong K. Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimer's Research and Therapy. 2014;6(4, article 37) doi: 10.1186/alzrt269.
    1. Doody R. S., Thomas R. G., Farlow M., et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. The New England Journal of Medicine. 2014;370(4):311–321. doi: 10.1056/nejmoa1312889.
    1. Salloway S., Sperling R., Fox N. C., et al. Two phase 3 trials of Bapineuzumab in mild-to-moderate Alzheimer's disease. The New England Journal of Medicine. 2014;370(4):322–333. doi: 10.1056/nejmoa1304839.
    1. Sevigny J., Chiao P., Bussière T., et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–56. doi: 10.1038/nature19323.
    1. Corbett A., Nunez K., Thomas A. Coping with dementia in care homes. Maturitas. 2013;76(1):3–4. doi: 10.1016/j.maturitas.2013.06.002.
    1. Margallo-Lana M., Swann A., O'Brien J., et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. International Journal of Geriatric Psychiatry. 2001;16(1):39–44. doi: 10.1002/1099-1166(200101)16:1<39::aid-gps269>;2-f.
    1. Ballard C., Corbett A. Agitation and aggression in people with Alzheimer's disease. Current Opinion in Psychiatry. 2013;26(3):252–259. doi: 10.1097/yco.0b013e32835f414b.
    1. Corbett A., Husebo B., Malcangio M., et al. Assessment and treatment of pain in people with dementia. Nature Reviews Neurology. 2012;8(5):264–274. doi: 10.1038/nrneurol.2012.53.
    1. Zarow C., Lyness S. A., Mortimer J. A., Chui H. C. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Archives of Neurology. 2003;60(3):337–341. doi: 10.1001/archneur.60.3.337.
    1. Parvizi J., Van Hoesen G. W., Damasio A. Selective pathological changes of the periaqueductal gray matter in Alzheimer's disease. Annals of Neurology. 2000;48(3):344–353.
    1. Husebo B. S., Ballard C., Sandvik R., Nilsen O. B., Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343(7816) doi: 10.1136/bmj.d4065.d4065
    1. Lonergan E., Luxenberg J., Colford J. Haloperidol for agitation in dementia. The Cochrane Database of Systematic Reviews. 2002;(2)CD002852
    1. Ballard C. G., Gauthier S., Cummings J. L., et al. Management of agitation and aggression associated with alzheimer disease. Nature Reviews Neurology. 2009;5(5):245–255. doi: 10.1038/nrneurol.2009.39.
    1. Reilly J. G., Ayis S. A., Ferrier I. N., Jones S. J., Thomas S. H. L. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. The Lancet. 2000;355(9209):1048–1052. doi: 10.1016/s0140-6736(00)02035-3.
    1. Ballard C., Howard R. Neuroleptic drugs in dementia: benefits and harm. Nature Reviews Neuroscience. 2006;7(6):492–500. doi: 10.1038/nrn1926.
    1. Schneider L. S., Dagerman K., Insel P. S. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. The American Journal of Geriatric Psychiatry. 2006;14(3):191–210. doi: 10.1097/01.jgp.0000200589.01396.6d.
    1. Ballard C., Margallo-Lana M., Juszczak E., et al. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial. British Medical Journal. 2005;330(7496):874–877. doi: 10.1136/bmj.38369.459988.8f.
    1. Schneider L. S., Tariot P. N., Dagerman K. S., et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. The New England Journal of Medicine. 2006;355(15):1525–1538. doi: 10.1056/nejmoa061240.
    1. FDA Public Health Advisory. Deaths with antipsychotics in elderly patients with behavioral disturbances. 2005, .
    1. Ballard C., Hanney M. L., Theodoulou M., et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. The Lancet Neurology. 2009;8(2):151–157. doi: 10.1016/S1474-4422(08)70295-3.
    1. Selbæk G., Aarsland D., Ballard C., et al. Antipsychotic drug use is not associated with long-term mortality risk in Norwegian nursing home patients. Journal of the American Medical Directors Association. 2016;17(5):464.e1–464.e7. doi: 10.1016/j.jamda.2016.01.016.
    1. Bagetta G., Cosentino M., Sakurada T., editors. Preface in Aromatherapy: Basic Mechanisms and Evidence Based Clinical Use. Oxfordshire, UK. Taylor & Francis: 2016.
    1. Ballard C. G., O'Brien J. T., Reichelt K., Perry E. K. 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. 2002;63(7):553–558. doi: 10.4088/jcp.v63n0703.
    1. Holmes C., Hopkins V., Hensford C., MacLaughlin V., Wilkinson D., Rosenvinge H. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. International Journal of Geriatric Psychiatry. 2002;17(4):305–308. doi: 10.1002/gps.593.
    1. Burns A., Byrne J., Ballard C., Holmes C. Sensory stimulation in dementia. British Medical Journal. 2002;325(7376):1312–1313. doi: 10.1136/bmj.325.7376.1312.
    1. Zarei A., Changizi Ashtiyani S., Taheri S., Rasekh F. Comparison between effects of different doses of Melissa officinalis and atorvastatin on the activity of liver enzymes in hypercholesterolemia rats. Avicenna Journal of Phytomedicine. 2014;4(1):15–23.
    1. Akhondzadeh S., Noroozian M., Mohammadi M., Ohadinia S., Jamshidi A. H., Khani M. 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, and Psychiatry. 2003;74(7):863–866. doi: 10.1136/jnnp.74.7.863.
    1. Perry E. K., Pickering A. T., Wang W. W., Houghton P., Perry N. S. L. Medicinal plants and Alzheimer's disease: integrating ethnobotanical and contemporary scientific evidence. Journal of Alternative and Complementary Medicine. 1998;4(4):419–428. doi: 10.1089/acm.1998.4.419.
    1. Perry E. K., Pickering A. T., Wang W. W., Houghton P. J., Perry N. S. L. Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy. Journal of Pharmacy and Pharmacology. 1999;51(5):527–534. doi: 10.1211/0022357991772808.
    1. Dastmalchi K., Ollilainen V., Lackman P., et al. Acetylcholinesterase inhibitory guided fractionation of Melissa officinalis L. Bioorganic and Medicinal Chemistry. 2009;17(2):867–871. doi: 10.1016/j.bmc.2008.11.034.
    1. Petersen M., Simmonds M. S. J. Rosmarinic acid. Phytochemistry. 2003;62(2):121–125. doi: 10.1016/S0031-9422(02)00513-7.
    1. Wake G., Court J., Pickering A., Lewis R., Wilkins R., Perry E. CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. Journal of Ethnopharmacology. 2000;69(2):105–114. doi: 10.1016/S0378-8741(99)00113-0.
    1. Carnat A. P., Carnat A., Fraisse D., Lamaison J. L. The aromatic and polyphenolic composition of lemon balm (Melissa officinalis L. subsp. officinalis) tea. Pharmaceutica Acta Helvetiae. 1998;72(5):301–305. doi: 10.1016/S0031-6865(97)00026-5.
    1. Hohmann J., Zupkó I., Rédei D., et al. Protective effects of the aerial parts of Salvia officinalis, Melissa officinalis and Lavandula angustifolia and their constituents against enzyme- dependent and enzyme-independent lipid peroxidation. Planta Medica. 1999;65(6):576–578. doi: 10.1055/s-2006-960830.
    1. Kennedy D. O., Wake G., Savelev S., et al. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology. 2003;28(10):1871–1881. doi: 10.1038/sj.npp.1300230.
    1. Guginski G., Luiz A. P., Silva M. D., et al. Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice. Pharmacology Biochemistry and Behavior. 2009;93(1):10–16. doi: 10.1016/j.pbb.2009.03.014.
    1. Cavanagh H. M. A., Wilkinson J. M. Biological activities of lavender essential oil. Phytotherapy Research. 2002;16(4):301–308. doi: 10.1002/ptr.1103.
    1. Elisabetsky E., Marschner J., Onofre Souza D. Effects of linalool on glutamatergic system in the rat cerebral cortex. Neurochemical Research. 1995;20(4):461–465. doi: 10.1007/BF00973103.
    1. Huang L., Abuhamdah S., Howes M.-J. R., et al. Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels. Journal of Pharmacy and Pharmacology. 2008;60(11):1515–1522. doi: 10.1211/jpp/60.11.0013.
    1. O'Connor D. W., Eppingstall B., Taffe J., Van Der Ploeg E. S. A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia. BMC Complementary and Alternative Medicine. 2013;13, article 315 doi: 10.1186/1472-6882-13-315.
    1. Umezu T. Behavioral effects of plant-derived essential oils in the geller type conflict test in mice. Japanese Journal of Pharmacology. 2000;83(2):150–153. doi: 10.1254/jjp.83.150.
    1. Shiina Y., Funabashi N., Lee K., et al. Relaxation effects of lavender aromatherapy improve coronary flow velocity reserve in healthy men evaluated by transthoracic Doppler echocardiography. International Journal of Cardiology. 2008;129(2):193–197. doi: 10.1016/j.ijcard.2007.06.064.
    1. Field T., Field T., Cullen C., et al. Lavender bath oil reduces stress and crying and enhances sleep in very young infants. Early Human Development. 2008;84(6):399–401. doi: 10.1016/j.earlhumdev.2007.10.008.
    1. Kim J. T., Ren C. J., Fielding G. A., et al. Treatment with lavender aromatherapy in the post-anesthesia care unit reduces opioid requirements of morbidly obese patients undergoing laparoscopic adjustable gastric banding. Obesity Surgery. 2007;17(7):920–925. doi: 10.1007/s11695-007-9170-7.
    1. Zeilmann C. A., Dole E. J., Skipper B. J., McCabe M., Low Dog T., Rhyne R. L. Use of herbal medicine by elderly Hispanic and non-Hispanic white patients. Pharmacotherapy. 2003;23(4):526–532. doi: 10.1592/phco.23.4.526.32117.
    1. Fu C.-Y., Moyle W., Cooke M. A randomised controlled trial of the use of aromatherapy and hand massage to reduce disruptive behaviour in people with dementia. BMC Complementary and Alternative Medicine. 2013;13, article 165 doi: 10.1186/1472-6882-13-165.
    1. Barocelli E., Calcina F., Chiavarini M., et al. Antinociceptive and gastroprotective effects of inhaled and orally administered Lavandula hybrida Reverchon ‘grosso’ essential oil. Life Sciences. 2004;76(2):213–223. doi: 10.1016/j.lfs.2004.08.008.
    1. Lin P. W.-K., Chan W.-C., Ng B. F.-L., Lam L. C.-W. Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial. International Journal of Geriatric Psychiatry. 2007;22(5):405–410. doi: 10.1002/gps.1688.
    1. Jimbo D., Kimura Y., Taniguchi M., Inoue M., Urakami K. Effect of aromatherapy on patients with Alzheimer's disease. Psychogeriatrics. 2009;9(4):173–179. doi: 10.1111/j.1479-8301.2009.00299.x.
    1. World Health Organization and Alzheimer's Disease International. Dementia: A Public Health Priority. Geneva, Switzerland: World Health Organization; 2012.
    1. Ballard C., Orrell M., Sun Y., et al. Impact of antipsychotic review and nonpharmacological intervention on antipsychotic use, neuropsychiatric symptoms, and mortality in people with dementia living in nursing homes: a factorial cluster-randomized controlled trial by the Well-Being and Health for People With Dementia (WHELD) program. The American Journal of Psychiatry. 2016;173(3):252–262. doi: 10.1176/appi.ajp.2015.15010130.
    1. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica. 1991;82(4):239–259. doi: 10.1007/BF00308809.
    1. Gold G., Bouras C., Kövari E., et al. Clinical validity of Braak neuropathological staging in the oldest-old. Acta Neuropathologica. 2000;99(5):579–584. doi: 10.1007/s004010051163.
    1. Eriksson P. S., Perfilieva E., Björk-Eriksson T., et al. Neurogenesis in the adult human hippocampus. Nature Medicine. 1998;4(11):1313–1317. doi: 10.1038/3305.
    1. Sakurada T., Kuwahata H., Katsuyama S., et al. Chapter 18 intraplantar injection of bergamot essential oil into the mouse hindpaw. Effects on capsaicin-induced nociceptive behaviors. International Review of Neurobiology. 2009;85:237–248. doi: 10.1016/s0074-7742(09)85018-6.
    1. Bagetta G., Morrone L. A., Rombolà L., et al. Neuropharmacology of the essential oil of bergamot. Fitoterapia. 2010;81(6):453–461. doi: 10.1016/j.fitote.2010.01.013.
    1. Kuwahata H., Komatsu T., Katsuyama S., et al. Peripherally injected linalool and bergamot essential oil attenuate mechanical allodynia via inhibiting spinal ERK phosphorylation. Pharmacology Biochemistry and Behavior. 2013;103(4):735–741. doi: 10.1016/j.pbb.2012.11.003.
    1. Katsuyama S., Otowa A., Kamio S., et al. Effect of plantar subcutaneous administration of bergamot essential oil and linalool on formalin-induced nociceptive behavior in mice. Biomedical Research. 2015;36(1):47–54. doi: 10.2220/biomedres.36.47.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する