Ramelteon in the Treatment of Delirium: New Perspectives from Reported Findings and a Case Observation

Author(s): Deborah L. Sanchez, Adam J. Fusick, William B. Hudson, Jourdan E. Schmitz, Maria C. Catalano, Glenn Catalano*.

Journal Name: Current Drug Therapy

Volume 14 , Issue 3 , 2019

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Abstract:

Ramelteon is a melatonin receptor agonist that is approved for the treatment of insomnia. It is widely used due to its relatively benign side effect profile and lack of dependence or withdrawal. Due to its tolerability, clinicians have attempted to utilize ramelteon to normalize the sleep/wake patterns in patients with delirium as a safer alternative to antipsychotics or other medications. We present the case of a 75-year-old man with long-standing dementia who was hospitalized due to mental status changes, agitation, and sleep disturbance. After addressing possible underlying causes with minimal improvement, the team initiated treatment with ramelteon (8mg nightly) which resulted in rapid improvement of symptoms. Uses and mechanisms of action of ramelteon will be reviewed, as well as current pharmacologic treatments of delirium. Prior research studies and case reports regarding the use of ramelteon in the treatment of delirium will be discussed and suggestions made regarding possible areas of future study.

Keywords: Ramelteon, delirium, melatonin, dementia, agitation, psychopharmacology.

[1]
Brasure M, MacDonald R, Fuchs E, et al. Management of Insomnia Disorder Rockville, MD: Agency for Healthcare Research and Quality 2015; (16)-EHC027-EF. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26844312
[2]
Chakraborti D, Tampi DJ, Tampi RR. Melatonin and melatonin agonist for delirium in the elderly patients. Am J Alzheimers Dis Other Demen 2015; 30: 119-29.
[3]
Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res 2012; 52: 365-75.
[4]
Diagnostic and Statistical Manual of Mental Disorders: DSM-5. American Psychiatric Press, Inc.: Arlington, Virginia 2013.
[5]
Furuya M, Miyaoka T, Yasuda H, et al. Marked improvement in delirium with ramelteon: five case reports. Psychogeriatrics 2012; 12: 259-62.
[6]
Walker CK, Gales MA. Melatonin receptor agonists for delirium prevention. Ann Pharmacother 2016; 51: 72-8.
[7]
Trzepacz P, Breitbart W, Franklin J, Levenson J, Martini DR, Wang P. Practice guideline for the treatment of patients with delirium. Am J Psychiatry 1999; 156(5)(Suppl.): 1-20.
[8]
U.S. Food and Drug Administration. Haloperidol (marketed as Haldol, Haldol Decanoate, and Haldol Lactate) Information. Available from. https://www.fda.gov/Drugs/DrugSafety/ucm216907.htm (Accessed on April 22, 2018).
[9]
Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Syst Rev 2007; 2CD005594
[10]
Ozbolt LB, Paniagua MA, Kaiser RM. Atypical antipsychotics for the treatment of delirious elders. J Am Med Dir Assoc 2018; 9: 18-28.
[11]
Hawkins SB, Bucklin M, Muzyk AJ. Quetiapine for the treatment of delirium. J Hosp Med 2013; 8: 215-20.
[12]
Boettger S, Breitbart W. An open trial of aripiprazole for the treatment of delirium in hospitalized cancer patients. Palliat Support Care 2011; 9: 351-7.
[13]
Bourgeois JA, Koike AK, Simmons JE, Simmons JE, Eggleston C. Adjunctive valproic acid for delirium and/or agitation on a consultation-liaison service: a report of six cases. J Neuropsychiatry Clin Neurosci 2005; 17: 232-8.
[14]
Lum E, Gorman SK, Slavik RS. Valproic acid management of acute alcohol withdrawal. Ann Pharmacother 2006; 40: 441-8.
[15]
Leung JM, Sands LP, Rico M, et al. Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients. Neurology 2006; 67: 1251-3.
[16]
Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Crit Care Clin 2008; 24: 657-722.
[17]
Zhang H, Lu Y, Liu M, et al. Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials. Crit Care 2013; 17: R47.
[18]
Maldonado JR, Wysong A, van der Starre PJ, et al. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics 2009; 50: 206-17.
[19]
Overshott R, Karim S, Burns A. Cholinesterase inhibitors for delirium. Cochrane Database Syst Rev 2008; 1CD005317
[20]
Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 2000; 35: 374-81.
[21]
Schneir AB, Offerman SR, Ly BT, et al. Complications of diagnostic physostigmine administration to emergency department patients. Ann Emerg Med 2003; 42: 14-9.
[22]
Brzezinski A. Melatonin in humans. N Engl J Med 1997; 336: 186-95.
[23]
De Rooij SE, van Munster BC. Melatonin deficiency hypothesis in delirium: a synthesis of current evidence. Rejuvenation Res 2013; 16: 273-8.
[24]
Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166: 1338-44.
[25]
Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive care delirium screening checklist: evaluation of a new screening tool. Intensive Care Med 2001; 27: 859-64.
[26]
Inouye SK, Van Dyck CH, Alessi CA, et al. Clarifying confusion: the Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med 1990; 113: 941-8.
[27]
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: 229-42.
[28]
Hatta K, Kishi Y, Wada K, et al. Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry 2014; 71: 397-403.
[29]
Perkisas SM, Vandewoude MF. Ramelteon for prevention of delirium in hospitalized older patients. JAMA 2015; 313: 1745-6.
[30]
Furuya M, Miyaoka T, Yasuda H, et al. Ramelteon as adjunctive therapy for delirium referred to a consultation-liaison psychiatry service: a retrospective analysis. Int J Geriatr Psychiatry 2015; 30: 994-5.
[31]
Miyata R, Omasa M, Fujimoto R, Ishikawa H, Aoki M. Efficacy of ramelteon for delirium after lung cancer surgery. Interact Cardiovasc Thorac Surg 2017; 24: 8-12.
[32]
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: 407-9.
[33]
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: 1107-10.
[34]
Yeh TC, Yeh CC, Tzeng NS, Mao WC. Adjunctive treatment with melatonin receptor agonists for older delirious patients with sundowning phenomenon. J Psychiatry Neurosci 2015; 40: E25-6.
[35]
Tsuda A, Nishimura K, Naganawa E, Otsubo T, Ishigooka J. Successfully treated delirium in an extremely elderly patient switched from risperidone to ramelteon. Psychiatry Clin Neurosci 2013; 67: 126.
[36]
Miura S, Furuya M, Yasuda H, Miyaoka T, Horiquchi J. Novel therapy with ramelteon for hypoactive delirium: a case report. J Clin Psychopharmacol 2015; 35: 616-8.
[37]
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.
[38]
Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The memorial delirium assessment scale. J Pain Symptom Manage 1997; 13: 128-37.


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Article Details

VOLUME: 14
ISSUE: 3
Year: 2019
Page: [184 - 191]
Pages: 8
DOI: 10.2174/1574885514666190308161421
Price: $65

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