Journal of Oriental Neuropsychiatry (동의신경정신과학회지)

The Korean Society of Oriental Neuropsychiatry (대한한방신경정신과학회)
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Classical, Non-Clinical, and Clinical Evidence of Yokukansan for Alleviating Aggression: Scoping Review

치매 환자의 공격성 관리에 활용가능한 억간산(抑肝散)의 고전적, 비임상적, 임상적 근거현황

  • Lee, Dong-Yoon (Dong-Eui University College of Korean Medicine) ;
  • Kim, Je-Beom (Dong-Eui University College of Korean Medicine) ;
  • Ha, Da-Jung (Department of Internal Medicine, Dong-Eui University College of Korean Medicine) ;
  • Kwon, Chan-Young (Department of Oriental Neuropsychiatry, Dong-Eui University College of Korean Medicine)
  • 이동윤 (동의대학교 한의과대학) ;
  • 김제범 (동의대학교 한의과대학) ;
  • 하다정 (동의대학교 한의과대학 한방내과) ;
  • 권찬영 (동의대학교 한의과대학 한방신경정신과)
  • Received : 2021.05.31
  • Accepted : 2021.06.25
  • Published : 2021.06.30
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Abstract

Objectives: To review and analyze clinical and preclinical evidence of effectiveness, safety, and underlying mechanisms of yokukansan (YKS), a herbal medicine, in alleviating aggression. Methods: Classical records on YKS were searched in the Korean Traditional Medicine Knowledge Database (KTMKD). By searching five electronic databases, prospective clinical studies and preclinical studies of YKS for alleviating aggression/agitation published up to March 30, 2021 were included. Results: Only two classical records on YKS were found from the KTMKD. A total of 11 clinical studies and 15 preclinical studies were found from the five electronic databases. Among 11 clinical studies, seven enrolled patients with dementia and four enrolled patients with other neuropsychiatric disorders. Most clinical studies reported significant improvement in one or more outcomes related to aggression in the YKS group after treatment. Among 15 preclinical studies, all studies except two reported a significant decrease in aggression/agitation-related behavior of YKS or yokukansankachimpihange. Suggested underlying mechanisms of YKS or yokukansankachimpihange for aggression/agitation in these studies included regulation of serotonin receptor, amelioration of abnormal glucocorticoid level related to the hypothalamic-pituitary-adrenal axis, regulation of orexin secretion, amelioration of degeneration in brain cells including glia cells, and suppression of excessive glutamatergic or dopaminergic activity. Conclusions: There were some clinical and preclinical evidence supporting the effectiveness and safety of YKS for alleviating aggression. Given that aggression is the most frequent and destructive symptoms of behavioral and psychological symptoms of dementia, applicability of YKS as a herbal medicine should be further investigated in future high-quality research.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HF20C0207).

References

  1. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002 Sep 25; 288(12):1475-83. https://doi.org/10.1001/jama.288.12.1475
  2. Shin IS, Carter M, Masterman D, Fairbanks L, Cummings JL. Neuropsychiatric symptoms and quality of life in Alzheimer disease. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2005 Jun;13(6):469-74. https://doi.org/10.1097/00019442-200506000-00005
  3. Kunik ME, Snow AL, Davila JA, McNeese T, Steele AB, Balasubramanyam V, et al. Consequences of aggressive behavior in patients with dementia. J Neuropsychiatry Clin Neurosci. 2010 Winter;22(1):40-7. https://doi.org/10.1176/appi.neuropsych.22.1.40
  4. McKeith I, Cummings J. Behavioural changes and psychological symptoms in dementia disorders. Lancet Neurol. 2005 Nov;4(11):735-42. https://doi.org/10.1016/S1474-4422(05)70219-2
  5. Han YA, Hur HK. Formal Nursing Home Caregivers' Dementia Knowledge, Empathy, and Burden of Care from Behavioral and Psychological Symptoms of Dementia. J Korean Gerontol Nurs. 2020;22(3):216-25. https://doi.org/10.17079/jkgn.2020.22.3.216
  6. Majer R, Adeyi O, Bagoly Z, Simon V, Csiba L, Kardos L, et al. Neuropsychiatric symptoms, quality of life and caregivers' burden in dementia. Open Med Wars Pol. 2020;15(1):905-14. https://doi.org/10.1515/med-2020-0124
  7. Savva GM, Zaccai J, Matthews FE, Davidson JE, McKeith I, Brayne C. Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population. Br J Psychiatry J Ment Sci. 2009 Mar;194(3): 212-9. https://doi.org/10.1192/bjp.bp.108.049619
  8. Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry. 2000 May; 157(5):708-14. https://doi.org/10.1176/appi.ajp.157.5.708
  9. Rabins PV, Blacker D, Rovner BW, Rummans T, Schneider LS, Tariot PN, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition. Am J Psychiatry. 2007 Dec;164(12 Suppl):5-56.
  10. Lyketsos CG, Steele C, Galik E, Rosenblatt A, Steinberg M, Warren A, et al. Physical aggression in dementia patients and its relationship to depression. Am J Psychiatry. 1999 Jan;156(1):66-71. https://doi.org/10.1176/ajp.156.1.66
  11. Shub D, Ball V, Abbas A-AA, Gottumukkala A, Kunik ME. The link between psychosis and aggression in persons with dementia: a systematic review. Psychiatr Q. 2010 Jun;81(2):97-110. https://doi.org/10.1007/s11126-009-9121-7
  12. Miyamoto Y, Tachimori H, Ito H. Formal caregiver burden in dementia: impact of behavioral and psychological symptoms of dementia and activities of daily living. Geriatr Nurs N Y N. 2010 Aug;31(4):246-53. https://doi.org/10.1016/j.gerinurse.2010.01.002
  13. Matsumoto N, Ikeda M, Fukuhara R, Shinagawa S, Ishikawa T, Mori T, et al. Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community. Dement Geriatr Cogn Disord. 2007;23(4):219-24. https://doi.org/10.1159/000099472
  14. de Oliveira AM, Radanovic M, de Mello PCH, Buchain PC, Vizzotto ADB, Celestino DL, et al. Nonpharmacological Interventions to Reduce Behavioral and Psychological Symptoms of Dementia: A Systematic Review. BioMed Res Int. 2015;2015:218980.
  15. Azermai M, Petrovic M, Elseviers MM, Bourgeois J, Van Bortel LM, Vander Stichele RH. Systematic appraisal of dementia guidelines for the management of behavioural and psychological symptoms. Ageing Res Rev. 2012 Jan; 11(1):78-86. https://doi.org/10.1016/j.arr.2011.07.002
  16. Watt JA, Gomes T, Bronskill SE, Huang A, Austin PC, Ho JM, et al. Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study. CMAJ Can Med Assoc J J Assoc Medicale Can. 2018 Nov 26;190(47): E1376-83. https://doi.org/10.1503/cmaj.180551
  17. Kim Y, Cho SH. Danggui-Shaoyao-San for dementia: A PRISMA-compliant systematic review and meta-analysis. Med U S [Internet]. 2020;99(4). Available from: https://www.embase.com/search/results?subaction=view-record&id=L631132389&from=export
  18. Kim TH, Kang JW. Herbal Medicine for Vascular Dementia: An Overview of Systematic Reviews. Curr Vasc Pharmacol. 2020;18(4):394-409. https://doi.org/10.2174/1570161117666190618164443
  19. Lee MS, Shin BC, Ernst E. Acupuncture for Alzheimer's disease: a systematic review. Int J Clin Pract. 2009 Jun;63(6):874-9. https://doi.org/10.1111/j.1742-1241.2009.02043.x
  20. Kwon C-Y, Lee B, Suh HW, Chung SY, Kim JW. Efficacy and Safety of Auricular Acupuncture for Cognitive Impairment and Dementia: A Systematic Review. Evid-Based Complement Altern Med ECAM. 2018;2018:3426078.
  21. Ahn HI, Hyun MK. Effectiveness of integrative medicine program for dementia prevention on cognitive function and depression of elderly in a public health center. Integr Med Res. 2019 Jun;8(2):133-7. https://doi.org/10.1016/j.imr.2019.04.008
  22. Hyde AJ, May BH, Dong L, Feng M, Liu S, Guo X, et al. Herbal medicine for management of the behavioural and psychological symptoms of dementia (BPSD): A system - atic review and meta-analysis. J Psychopharmacol Oxf Engl. 2017 Feb;31(2):169-83. https://doi.org/10.1177/0269881116675515
  23. Mizukami K, Asada T, Kinoshita T, Tanaka K, Sonohara K, Nakai R, et al. A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol. 2009;12(2):191-9. https://doi.org/10.1017/S146114570800970X
  24. Matsuda Y, Kishi T, Shibayama H, Iwata N. Yokukansan in the treatment of behavioral and psychological symptoms of dementia: a systematic review and meta-analysis of randomized controlled trials. Hum Psychopharmacol. 2013 Jan;28(1):80-6. https://doi.org/10.1002/hup.2286
  25. Mizukami K, Asada T, Kinoshita T, Tanaka K, Sonohara K, Nakai R, et al. A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol. 2009 Mar;12(2):191-9. https://doi.org/10.1017/S146114570800970X
  26. Shinno H, Inami Y, Inagaki T, Nakamura Y, Horiguchi J. Effect of Yi-Gan San on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(3):881-5. https://doi.org/10.1016/j.pnpbp.2007.12.027
  27. Okahara K, Ishida Y, Hayashi Y, Inoue T, Tsuruta K, Takeuchi K, et al. Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Apr 16;34(3):532-6. https://doi.org/10.1016/j.pnpbp.2010.02.013
  28. Nagata K, Yokoyama E, Yamazaki T, Takano D, Maeda T, Takahashi S, et al. Effects of yokukansan on behavioral and psychological symptoms of vascular dementia: an open-label trial. Phytomedicine Int J Phytother Phytopharm. 2012 Apr 15;19(6):524-8.
  29. Teranishi M, Kurita M, Nishino S, Takeyoshi K, Numata Y, Sato T, et al. Efficacy and tolerability of risperidone, yokukansan, and fluvoxamine for the treatment of behavioral and psychological symptoms of dementia: A blinded, randomized trial. J Clin Psychopharmacol. 2013;33(5):600-7. https://doi.org/10.1097/JCP.0b013e31829798d5
  30. Furukawa K, Tomita N, Uematsu D, Okahara K, Shimada H, Ikeda M, et al. Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease. Geriatr Gerontol Int. 2017;17(2):211-8. https://doi.org/10.1111/ggi.12696
  31. Hayashi Y, Ishida Y, Inoue T, Udagawa M, Takeuchi K, Yoshimuta H, et al. Treatment of behavioral and psychological symptoms of Alzheimer-type dementia with Yokukansan in clinical practice. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(3):541-5. https://doi.org/10.1016/j.pnpbp.2010.02.016
  32. Hatano T, Hattori N, Kawanabe T, Terayama Y, Suzuki N, Iwasaki Y, et al. An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson's disease. J Neural Transm. 2014;121(3):275-81. https://doi.org/10.1007/s00702-013-1105-y
  33. Miyaoka T, Furuya M, Yasuda H, Hayashia M, Inagaki T, Horiguchi J. Yi-gan san for the treatment of borderline personality disorder: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):150-4. https://doi.org/10.1016/j.pnpbp.2007.07.026
  34. Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, et al. Yokukansan (TJ-54) for irritability associated with pervasive developmental disorder in children and adolescents: a 12-week prospective, open-label study. J Child Adolesc Psychopharmacol. 2013 Jun;23(5):329-36. https://doi.org/10.1089/cap.2012.0108
  35. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, et al. Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger's disorder: a 12-week prospective, open-label study. BMC Psychiatry. 2012 Nov 29;12:215. https://doi.org/10.1186/1471-244X-12-215
  36. Tamano H, Kan F, Oku N, Takeda A. Ameliorative effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient young mice. Brain Res Bull. 2010; 83(6):351-5. https://doi.org/10.1016/j.brainresbull.2010.08.013
  37. Katahira H, Sunagawa M, Watanabe D, Kanada Y, Katayama A, Yamauchi R, et al. Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion. Neuropsychiatr Dis Treat. 2017;13:863-72. https://doi.org/10.2147/NDT.S129418
  38. Iba H, Watanabe T, Matsuzawa K, Saimiya M, Tanaka M, Nagao M, et al. Effect of Yokukansan and Yokukansanka-chimpihange on Aggressive Behavior, 5-HT Receptors and Arginine Vasopressin Expression in Social IsolationReared Mice. Biol Pharm Bull. 2019;42(12):2009-15. https://doi.org/10.1248/bpb.b19-00499
  39. Kanno H , Sekiguchi K , Yam aguchi T, Teraw aki K , Yuzurihara M, Kase Y, et al. Effect of yokukansan, a traditional Japanese medicine, on social and aggressive behaviour of para-chloroamphetamine-injected rats. J Pharm Pharmacol. 2009;61(9):1249-56. https://doi.org/10.1211/jpp/61.09.0016
  40. Sekiguchi K, Imamura S, Yamaguchi T, Tabuchi M, Kanno H, Terawaki K, et al. Effects of yokukansan and donepezil on learning disturbance and aggressiveness induced by intracerebroventricular injection of amyloid β protein in mice. Phytother Res PTR. 2011 Apr;25(4):501-7. https://doi.org/10.1002/ptr.3287
  41. Sekiguchi K, Yamaguchi T, Tabuchi M, Ikarashi Y, Kase Y. Effects of yokukansan, a traditional Japanese medicine, on aggressiveness induced by intracerebroventricular injection of amyloid β protein into mice. Phytother Res. 2009;23(8):1175-81. https://doi.org/10.1002/ptr.2777
  42. Ikarashi Y, Iizuka S, Imamura S, Yamaguchi T, Sekiguchi K, Kanno H, et al. Effects of yokukansan, a traditional Japanese medicine, on memory disturbance and behavioral and psychological symptoms of dementia in thiamine-deficient rats. Biol Pharm Bull. 2009 Oct;32(10):1701-9. https://doi.org/10.1248/bpb.32.1701
  43. Iizuka S, Kawakami Z, Imamura S, Yamaguchi T, Sekiguchi K, Kanno H, et al. Electron-microscopic examination of effects of yokukansan, a traditional Japanese medicine, on degeneration of cerebral cells in thiamine-deficient rats. Neuropathol Off J Jpn Soc Neuropathol. 2010 Oct;30(5):524-36.
  44. Nishi A, Yamaguchi T, Sekiguchi K, Imamura S, Tabuchi M, Kanno H, et al. Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin1A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan. Neuroscience. 2012;207 ((Nishi A., nishi_akinori@mail.tsumura.co.jp; Yamaguchi T.; Sekiguchi K.; Imamura S.; Tabuchi M.; Kanno H.; Ikarashi Y.; Kase Y.) Tsumura Research Laboratories, Tsumura and Co., 3586 Yoshiwara, Ami-machi, Inashikigun, Ibaraki 300-1192, Japan):124-36. https://doi.org/10.1016/j.neuroscience.2012.01.037
  45. Tamano H, Yusuke E, Ide K, Takeda A. Influences of yokukansankachimpihange on aggressive behavior of zincdeficient mice and actions of the ingredients on excessive neural exocytosis in the hippocampus of zinc-deficient rats. Exp Anim. 2016 Nov 1;65(4):353-61. https://doi.org/10.1538/expanim.16-0028
  46. Tahara E, Wu W, Satoh T, Yamada T, Kurosaki I, Nagai H, et al. Psychosocial stress enhances IgE-mediated triphasic cutaneous reaction in mice: Antagonism by Yokukansan (a kampo medicine) and diazepam. Allergol Int. 2001;50(3):211-21. https://doi.org/10.1046/j.1440-1592.2001.00222.x
  47. Takeda A, Iwaki H, Ide K, Tamano H, Oku N. Therapeutic effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice. Brain Res Bull. 2012;87(6):551-5. https://doi.org/10.1016/j.brainresbull.2012.02.003
  48. Tabuchi M, Mizuno K, Mizoguchi K, Hattori T, Kase Y. Yokukansan and yokukansankachimpihange ameliorate aggressive behaviors in rats with cholinergic degeneration in the nucleus basalis of meynert. Front Pharmacol [Internet]. 2017;8(APR). Available from: https://www.embase.com/search/results?subaction=view-record&id=L615893475&from=export
  49. Uchida N, Egashira N, Iwasaki K, Ishibashi A, Tashiro R, Nogami A, et al. Yokukansan inhibits social isolation-induced aggression and methamphetamine-induced hyperlocomotion in rodents. Biol Pharm Bull. 2009 Mar;32(3):372-5. https://doi.org/10.1248/bpb.32.372
  50. Fujiwara H, Takayama S, Iwasaki K, Tabuchi M, Yamaguchi T, Sekiguchi K, et al. Yokukansan, a traditional Japanese medicine, ameliorates memory disturbance and abnormal social interaction with anti-aggregation effect of cerebral amyloid β proteins in amyloid precursor protein transgenic mice. Neuroscience. 2011;180(2011):305-13. https://doi.org/10.1016/j.neuroscience.2011.01.064
  51. Mizoguchi K, Ikarashi Y. Cellular Pharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan on Brain Cells. Front Pharmacol. 2017;8:655. https://doi.org/10.3389/fphar.2017.00655