정신신체의학 (Korean Journal of Psychosomatic Medicine)

한국정신신체의학회 (Korean Psychosomatic Society)
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입원 환자의 섬망 치료에서 멜라토닌의 효과에 관한 후향적 연구

Melatonin for Treatment of Delirium in Hospitalized Patients : Retrospective Trial

  • 양정우 (경희대학교병원 정신건강의학과) ;
  • 김종우 (경희대학교병원 정신건강의학과) ;
  • 강원섭 (경희대학교병원 정신건강의학과) ;
  • 이상민 (경희대학교병원 정신건강의학과) ;
  • 김영종 (경희대학교병원 정신건강의학과) ;
  • 백종우 (경희대학교병원 정신건강의학과)
  • Yang, Jung Woo (Department of Psychiatry, Kyung Hee University Hospital) ;
  • Kim, Jong Woo (Department of Psychiatry, Kyung Hee University Hospital) ;
  • Kang, Won Sub (Department of Psychiatry, Kyung Hee University Hospital) ;
  • Lee, Sang Min (Department of Psychiatry, Kyung Hee University Hospital) ;
  • Kim, Young Jong (Department of Psychiatry, Kyung Hee University Hospital) ;
  • Paik, Jong-Woo (Department of Psychiatry, Kyung Hee University Hospital)
  • 투고 : 2018.09.03
  • 심사 : 2018.10.04
  • 발행 : 2018.12.31
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초록

연구목적 섬망은 신체 질환과 같은 기저 의학적 상태의 변화에 의해 나타나는 뇌의 기능장애로 환자의 사망률을 높이고 치매의 위험도를 높이는 등 불량한 예후와 연관되어 있다. 기존 섬망의 치료에 주로 사용된 항정신병약제는 치료 효과에 대한 논란이 있으며 추체외로 부작용 등에 대한 우려가 있다. 따라서 수면 주기 조절 및 섬망 예방효과가 있는 것으로 알려진 멜라토닌 투여를 통해 섬망 호전 정도와 안전성을 조사하고자 하였다. 방 법 불면을 동반한 섬망 증상으로 정신건강의학과에 진료 의뢰되어 멜라토닌 2mg을 투여 받은 환자를 대상으로 의무기록을 통해 섬망 증상의 초기 중증도 및 멜라토닌 투여 후의 섬망 증상 변화 여부를 한국판 섬망 평가척도-98 개정판(K-DRS-R-98)과 CGI-S를 통해 확인하였으며 부작용을 검토하였다. 결 과 총 21명의 환자가 불면을 동반한 섬망 증상으로 멜라토닌을 투여받았다. K-DRS-R-98 심각도 점수는 투약 전 $15.24{\pm}2.64$에서 투약 후 $6.57{\pm}5.42$로 감소하였으며 CGI-S 점수는 $4.14{\pm}0.48$에서 $2.81{\pm}0.93$로 감소하였다(p<0.05). 의무기록 상 부작용은 관찰되지 않았다. 결 론 약물의 기전 상 추체외로 증상과 QTc연장 등의 문제를 유발하지 않는 멜라토닌의 사용은 보다 안정성을 강화하면서 불면에 대한 효과와 함께 섬망을 효과적으로 치료할 가능성을 제시할 것으로 생각된다.

Objectives : Delirium is one of the most common mental illnesses that can affect cognitive function. Melatonin has been shown to be effective in the treatment of insomnia, and recent studies have shown a protective effect to prevent delirium. This study was conducted to investigate the efficacy of melatonin in delirium patients. Methods : All patients were referred to psychiatric department for insomnia and symptoms of delirium, and were diagnosed delirium by the DSM-5 diagnostic criteria. We compared base line severity of delirium with K-DRS-R-98-R (Korean version of Delirium Rating Scale revised 98) and after taking 2mg of melatonin, retrospectively. The side effects were also identified by referring to the medical records. Results : A total 21 patients had taken melatonin for insomnia and delirious symptoms. The K-DRS-R-98 scores were decreased from $15.24{\pm}2.64$ before treatment to $6.57{\pm}5.42$ after treatment. And CGI-S scores were also decreased from $4.14{\pm}0.48$ before treatment to $2.81{\pm}0.93$ after treatment (p<0.05). Conclusions : This study illustrates the possibility of melatonin as an effective treatment option for delirious symptoms such as disorientation, motor agitation, lability of affect and hallucinations as well as insomnia, with less concerns of drug side effect. Further study with a larger sample and prospective design will be required to confirm these results.

키워드

JSSCBG_2018_v26n2_112_f0001.png 이미지

Fig. 1. Comparison of K-DRS-R-98 before and after treatment with melatonin in patients with delirium. p<0.05. K-DRS-R-98 : Korean version of Delirium Rating Scale-Revised-98, pre : pretreatment, post : post-treatment.

JSSCBG_2018_v26n2_112_f0002.png 이미지

Fig. 3. K-DRS-R-98 sub-scale change. Mean difference of K-DRS-R-98 subscale score from baseline over time after treatment. K-DRS-R-98 : Korean version of Delirium Rating Scale- Revised-98, pre : pre-treatment, post : post-treatment.

JSSCBG_2018_v26n2_112_f0003.png 이미지

Fig. 2. Comparison of CGI-S before and after treatment with melatonin in patients with delirium. p<0.05. CGI-S : Clinical Global Impression-Severity, pre : pre-treatment, post : posttreatment.

Table 1. Demographic data of patient with delirium

JSSCBG_2018_v26n2_112_t0001.png 이미지

Table 2. Comparison of K-DRS-R-98 severity score and CGI-S after treatment in patients with initial K-DRS-R-98 severity score was less than 16

JSSCBG_2018_v26n2_112_t0002.png 이미지

참고문헌

  1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911-922. https://doi.org/10.1016/S0140-6736(13)60688-1
  2. Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry 2004;12:7-21. https://doi.org/10.1097/00019442-200401000-00002
  3. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc 2016;64:705-714. https://doi.org/10.1111/jgs.14076
  4. Markowitz JD, Narasimhan M. Delirium and Antipsychotics: A Systematic Review of Epidemiology and Somatic Treatment Options. Psychiatry (Edgmont) 2008;5:29-36.
  5. William B, Yesne A. Evidence-Based Treatment of Delirium in Patients With Cancer. J Clin Oncol 2012;30:11:1206-1214. https://doi.org/10.1200/JCO.2011.39.8784
  6. Gunther ML, Morandi A, Ely EW. Pathophysiology of delirium in the intensive care unit. Crit Care Clin 2008;24:45-65. https://doi.org/10.1016/j.ccc.2007.10.002
  7. Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci 2008;63:764-772. https://doi.org/10.1093/gerona/63.7.764
  8. Van Munster BC, Korevaar JC, Zwinderman AH, Levi M, Wiersinga WJ, De Rooij SE. Time course of cytokines during delirium in elderly patients with hip fractures. J Am Geriatr Soc 2008;56:1704-1709. https://doi.org/10.1111/j.1532-5415.2008.01851.x
  9. Turek FW, Gillette MU. Melatonin, sleep, and circadian rhythm: rationale for the development of specific melatonin agonist. Sleep Med 2004;5:523-532. https://doi.org/10.1016/j.sleep.2004.07.009
  10. de Rooij SE, van Munster BC. Melatonin deficiency hypothesis in delirium: a synthesis of current evidence. Rejuvenation Res 2013;16:273-278. https://doi.org/10.1089/rej.2012.1405
  11. Srinivasan V, Kaur C, Pandi-Perumal S, Brown GM, Cardinali DP. Melatonin and its agonist ramelteon in Alzheimer's disease: possible therapeutic value. Int J Alzheimer's Dis 2011;741974.
  12. Zhao LB, Zhen GD, Zhang Y, Pan YY, Du GH, Zhou SZ, Li ZF. Observation and analysis of clinical efficacy of melatonin on AOPP-induced delirium patients. Eur Rev Med Pharmacol Sci 2018;22:1494-1498.
  13. Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick-DL, Reiter RJ, Efthimiopoulos S, Robakis NK. Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci 1997;17:1683-1690. https://doi.org/10.1523/JNEUROSCI.17-05-01683.1997
  14. Wang JZ, Wang ZF. Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacologica Sinica 2006;27:41. https://doi.org/10.1111/j.1745-7254.2006.00260.x
  15. Balan S, Leibovitz A, Zila SO, Ruth M, Chana W, Yassica B, Rahel B, Richard G, Neumann E, Blagman B, Habot B. The relation between the clinical subtypes of delirium andthe urinary level of 6-SMT. J Neuropsychiatry Clin Neurosci 2003; 15:363-366. https://doi.org/10.1176/jnp.15.3.363
  16. Yoshitaka S, Egi M, Morimatsu H, Kanazawa T, Toda Y, Morita K. Perioperative plasma melatonin concentration in postoperative critically ill patients: its association with delirium. J Crit Care 2013;28:236-242. https://doi.org/10.1016/j.jcrc.2012.11.004
  17. Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg 2002;94:338-339.
  18. Hatta K, Kishi Y, Wada K, Takeuchi T, Odawara T, Usui C, Nakamura H. Preventive Effects of Ramelteon on Delirium A Randomized Placebo-Controlled Trial. JAMA Psychiatry 2014;71:397-403. https://doi.org/10.1001/jamapsychiatry.2013.3320
  19. Kimura R, Mori K, Kumazaki H, Yanagida M, Taguchi S, Matsunaga H. Treatment of delirium with ramelteon: Initial experience in three patients. Gen Hosp Psychiatry 2011;33: 407-409. https://doi.org/10.1016/j.genhosppsych.2011.03.013
  20. Furuya M, Miyaoka T, Yasuda H, Yamashita S, Tanaka I, Otsuka S, Wake R,Horiguchi J. Marked improvement in delirium with ramelteon: Five case reports. Psychogeriatrics 2012; 12:259-262. https://doi.org/10.1111/j.1479-8301.2012.00422.x
  21. Tsuda A, Nishimura K, Naganawa E, Otsubo T, Ishigooka J. Ramelteon for the treatment of delirium in elderly patients: a consecutive case series study. Int J Psychiatry Med 2014;47: 97-104. https://doi.org/10.2190/PM.47.2.a
  22. Ohta T, Murao K, Miyake K, Takemoto K. Melatonin Receptor Agonists for Treating Delirium in Elderly Patients with Acute Stroke. J Stroke Cerebrovasc Dis 2013;22:1107-1110. https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.08.012
  23. Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci 2001;13:229-242. https://doi.org/10.1176/jnp.13.2.229
  24. Lee Y, Ryu J, Lee J, Kim HJ, Shin IH, Kim JL, Trzepacz PT. Korean version of the delirium rating scale-revised-98: reliability and validity. Psychiatry Investig 2011;8:30-38. https://doi.org/10.4306/pi.2011.8.1.30
  25. Lim KO, Kim SY, Lee YH, Lee SW, Kim JL. A validation study for the Korean version of Delirium Rating Scale-Revised-98 (K-DRS-98). J Korean Neuropsychiatr Assoc 2006;45: 518-526.
  26. Guy W. Clinical Global Impression(CGI) Modified From: Rush J, John A. Handbook of psychiatry Measures Washington, DC: American Psychiatric Association;2000. p.100-102.
  27. Witlox J, Eurelings LS, de Jonghe JF. Delirium in elderly patients and the risk of post discharge mortality, institutionalization, and dementia: a meta-analysis. JAMA Psychiatry 2010; 304:443-451.
  28. Wang PS, Schneeweiss S, Avorn J, Fischer MA, Mogun H, Solomon DH, Brookhart MA. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005;353:2335-2341. https://doi.org/10.1056/NEJMoa052827
  29. Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapinevs haloperidol: Treating delirium in a critical care setting. Intensive Care Med 2004;30:444-449. https://doi.org/10.1007/s00134-003-2117-0
  30. Lee SJ, Jeong JH, Kim TW, Lim HK, Seo HJ, Hong SC, Han JH. Comparison of Treatment Response of Antipsychotics According to Sedative Effect in the Treatment of Patients with Delirium. Korean Journal of Psychopharmacology 2014; 25:168-174.
  31. Miyaji S, Yamamoto K, Hoshino S, Yamamoto H, Sakai Y, Miyaoka H. Comparison of the risk of adverse events between risperidone and haloperidol in delirium patients. Psychiatry Clin Neurosci 2007;61:275-282. https://doi.org/10.1111/j.1440-1819.2007.01655.x
  32. Cole M, McCusker J, Dendukuri N, Han L. The prognostic significance of subsyndromal delirium in elderly medical in patienrs. J Am Geriatr Soc 2003;51:754-760. https://doi.org/10.1046/j.1365-2389.2003.51255.x