Withdrawal syndrome (delirium) is one of the most important problems experienced by alcohol-dependent patients. Withdrawal delirium often improves within a week after stopping alcohol, but withdrawal deliria are prolonged in many alcohol-dependent patients and some patients with such delirium become demented. There is no consensus as to the optimal drug therapy for prolonged delirium. We cared for two alcohol-dependent patients whose prolonged deliria were ameliorated after the initiation of donepezil, an acetylcholinesterase inhibitor. Here, we report on these two patients and discuss drug therapies for prolonged delirium in alcohol-dependent patients.

Patient  1:  a  63-year-old  man  with  a  45 year  history of drinking, who had drunk more than 1250 mL of Japanese wine every day, was admitted to National Shimofusa Hospital. He sometimes suffered visual hallucinations when he stopped drinking. Because he had a cold, he had stopped drinking for 5 days before admission. Three days after he stopped drinking, he thought he saw Japanese gangs threatening him with knives, which frightened him. Therefore he was admitted to the psychiatric unit. He was relatively calm during the day but he was delirious and excited at night. He was given 1–2.25 mg/day haloperidol, 4 mg/day diazepam and 0.25 mg/day brotizolam, which were not effective, for these symptoms. Although he was given infusions of 5 mg haloperidol or 25 mg levomepromazine, he slept little and said that his wife and friends had come to the hospital at night the day before and that his room was burning, which excited him. Two months after he was admitted, the only drug treatment he was receiving was donepezil 5 mg/day. Two weeks after starting donepezil, he felt relaxed, no longer suffered hallucinations and slept well, so he was discharged. His Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) scores1 decreased from 25, when donepezil treatment was initiated, to 6 at 1 month later.

Patient 2: a 76-year-old woman was admitted to the psychogeriatric unit of National Shimofusa Hospital. Her drinking began when she was 20 years old and she drank two bottles of beer every day, which had damaged her liver. When she stopped drinking 3 years before the present admission, she became delirious. Three months before the present admission she stopped  drinking because she was admitted to another hospital to have her liver function examined. Two weeks later she was forgetful, could not understand what her family said and wandered out of the hospital. Therefore, she was discharged from that hospital and returned to her house. However, she also wandered out of her house and did not sleep, therefore she was admitted to the psychogeriatric unit of National Shimofusa Hospital. She was relatively calm during the day but she was delirious and anxious at night. We prescribed donepezil 5 mg/day for her and after 3 weeks her symptoms were alleviated. She felt relaxed, slept well and was discharged. Her CIWA-Ar scores decreased from 34 when donepezil treatment was started to 3 at 1 month later.

Donepezil, a cholinesterase inhibitor that is the only drug we can prescribe for Alzheimer's disease (AD) patients in Japan, not only exerts beneficial effects on cognitive functions of patients with AD,2,3 but also improves neuropsychiatric symptoms, such as delusion and hallucinations, associated with AD and diffuse Lewy body disease (DLB).4 In addition to these, dysfunction of the cholinergic system (i.e. cholinergic deficiency) also has been implicated in the pathophysiology of delirium associated with dementia including AD and DLB.5 It has been reported that cholinesterase inhibition could induce a beneficial ameliorative effect on prolonged delirium due to dementia including AD.6,7 Total serum anticholinergic activities were reported to be significantly higher in delirious patients than in non-delirious age-matched control subjects and to have decreased in those patients in whom delirium resolved completely.8 Meperdine, which has anticholinergic properties, was reported to induce delirium.9 Leavitt et al. suggested that anticholinergic mechanisms play a common, important role in the neuropathophysiology of delirium due to many different causes.10 Trzepacz commented that the characteristic symptoms of delirium supported the concept of a ‘final common pathway’ and that the cholinergic deficiency and dopaminergic excess, either absolute and/or relative to each other, were the dominant theory of neurotransmission abnormality that may underlie the final common pathway of delirium, which includes delirium caused by alcoholic withdrawal.11 Therefore, cholinomimetic agents might improve delirium of various causes,12,13 including delirium due to alcoholic withdrawal. In fact, physostigumine, another cholinesterase inhibitor, was reported to treat delirium tremens.14 Our patients might provide evidence that cholinomimetic agents can ameliorate not only delirium tremens but also prolonged delirium due to alcholic withdrawal.


  1. Top of page
  • 1
    Sullivan JT, Sykora K, Schneiderman J et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br. J. Addiction 1989; 84: 13531357.
  • 2
    Lawrence AD, Sahakian B. The cognitive psychopharmacology of Alzheimer's disease: focus on cholinergic systems. Neurochem. Res. 1997; 23: 787794.
  • 3
    Rogers SL, Farlow MR, Doody RS et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology 1998; 50: 136145.
  • 4
    Cummings JL. Cholinesterase inhibitors: a new class of psychotropic compound. Am. J. Psychiatry 2000; 157: 415.
  • 5
    Kaufer DI, Catt KE, Lopez OL, DeKosky ST. Dementia with Lewy bodies: response to delirium-like features to donepezil. Neurology 1998; 51: 15121512.
  • 6
    Wengel SP, Roccaforte WH, Burke WJ. Donepezil improves symptoms of delirium in dementia: implications for future research. J. Geriatr. Psychiatry Neurol. 1998; 11: 159161.
  • 7
    Wengel SP, Burke WJ, Roccaforte WH. Donepezil for postoperative delirium associated with Alzheimer's disease. J. Am. Geriatr. Soc. 1999; 47: 379380.
  • 8
    Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium in surgical patients. Am. J. Psychiatry 1987; 144: 12181220.
  • 9
    Eisendrath SJ, Goldman B, Douglas J et al. Meperidine-induced delirium. Am. J. Psychiatry 1987; 144: 10621065.
  • 10
    Leavitt ML, Trzepacz PT, Ciongoli K. Rat model of delirium: atropine dose–response relationships. J. Neuropsychiatry Clin. Neurosci. 1994; 6: 279284.
  • 11
    Trzepacz PT. Is there a final common pathway in delirium? Focus on acetylcholine and dopamine. Semin. Clin. Neuropsychiatry 2000; 5: 132148.
  • 12
    Coffman JA, Dilsaver SC. Cholinergic mechanisms of delirium. Am. J. Psychiatry 1988; 145: 382382.
  • 13
    Skjerve A, Nygaard HA. Improvement in sundowning in dementia with Lewy bodies after treatment with donepezil. Int. J. Geriatr. Psychiatry 2000; 15: 11471151.
  • 14
    Powers JS, Decoskey D, Kahrilas PJ. Physostigmine for treatment of delirium tremens. J. Clin. Pharmacol. 1981; 21: 5760.