Alcohol withdrawal: Difference between revisions

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[[Randomized controlled trial]]s have found benefit from [[sympathetic nervous system|sympatholytics]] such as [[atenolol]]<ref name="pmid2863754">{{cite journal |author=Kraus ML, Gottlieb LD, Horwitz RI, Anscher M |title=Randomized clinical trial of atenolol in patients with alcohol withdrawal |journal=N. Engl. J. Med. |volume=313 |issue=15 |pages=905-9 |year=1985 |pmid=2863754 |doi=}}</ref>, [[propanolol]]<ref name="pmid7004240">{{cite journal |author=Zilm DH, Jacob MS, MacLeod SM, Sellers EM, Ti TY |title=Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal |journal=Alcohol. Clin. Exp. Res. |volume=4 |issue=4 |pages=400-5 |year=1980 |pmid=7004240 |doi= |issn=}}</ref><ref name="pmid592834">{{cite journal |author=Sellers EM, Zilm DH, Degani NC |title=Comparative efficacy of propranolol and chlordiazepoxide in alcohol withdrawal |journal=J. Stud. Alcohol |volume=38 |issue=11 |pages=2096–108 |year=1977 |month=November |pmid=592834 |doi= |url= |issn=}}</ref> and [[clonidine]].<ref name="pmid3300587">{{cite journal |author=Baumgartner GR, Rowen RC |title=Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome |journal=Arch. Intern. Med. |volume=147 |issue=7 |pages=1223-6 |year=1987 |pmid=3300587 |doi=}}</ref> In the major trial, atenolol was given to patients without contraindications at a dose of 50 mg if the pulse was 50-79 and 100 mg if the pulse was 80 or more.<ref name="pmid2863754"/> Clonidine was administered to patients without contraindications as 0.2 mg per dose with the schedule of day 1 at 9pm; day 2 at 9am, 1pm, and 6pm; day 3 9am and 6pm; and day 4 at 9am.<ref name="pmid3300587"/>
[[Randomized controlled trial]]s have found benefit from [[sympathetic nervous system|sympatholytics]] such as [[atenolol]]<ref name="pmid2863754">{{cite journal |author=Kraus ML, Gottlieb LD, Horwitz RI, Anscher M |title=Randomized clinical trial of atenolol in patients with alcohol withdrawal |journal=N. Engl. J. Med. |volume=313 |issue=15 |pages=905-9 |year=1985 |pmid=2863754 |doi=}}</ref>, [[propanolol]]<ref name="pmid7004240">{{cite journal |author=Zilm DH, Jacob MS, MacLeod SM, Sellers EM, Ti TY |title=Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal |journal=Alcohol. Clin. Exp. Res. |volume=4 |issue=4 |pages=400-5 |year=1980 |pmid=7004240 |doi= |issn=}}</ref><ref name="pmid592834">{{cite journal |author=Sellers EM, Zilm DH, Degani NC |title=Comparative efficacy of propranolol and chlordiazepoxide in alcohol withdrawal |journal=J. Stud. Alcohol |volume=38 |issue=11 |pages=2096–108 |year=1977 |month=November |pmid=592834 |doi= |url= |issn=}}</ref> and [[clonidine]].<ref name="pmid3300587">{{cite journal |author=Baumgartner GR, Rowen RC |title=Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome |journal=Arch. Intern. Med. |volume=147 |issue=7 |pages=1223-6 |year=1987 |pmid=3300587 |doi=}}</ref><ref name="pmid8625628">{{cite journal |author=Spies CD, Dubisz N, Neumann T, ''et al'' |title=Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial |journal=Crit. Care Med. |volume=24 |issue=3 |pages=414–22 |year=1996 |month=March |pmid=8625628 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=24&issue=3&spage=414 |issn=}}</ref> In the major trial, atenolol was given to patients without contraindications at a dose of 50 mg if the pulse was 50-79 and 100 mg if the pulse was 80 or more.<ref name="pmid2863754"/> Clonidine was administered to patients without contraindications as 0.2 mg per dose with the schedule of day 1 at 9pm; day 2 at 9am, 1pm, and 6pm; day 3 9am and 6pm; and day 4 at 9am.<ref name="pmid3300587"/>


A factorial [[randomized controlled trial]]<ref name="pmid7004240">{{cite journal |author=Zilm DH, Jacob MS, MacLeod SM, Sellers EM, Ti TY |title=Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal |journal=Alcohol. Clin. Exp. Res. |volume=4 |issue=4 |pages=400-5 |year=1980 |pmid=7004240 |doi= |issn=}}</ref> has been misinterpreted leading to concerns that beta-blockers are associated with hallucinations.<ref name="pmid15249349">{{cite journal |author=Mayo-Smith MF, Beecher LH, Fischer TL, ''et al'' |title=Management of alcohol withdrawal delirium. An evidence-based practice guideline |journal=Arch. Intern. Med. |volume=164 |issue=13 |pages=1405-12 |year=2004 |pmid=15249349 |doi=10.1001/archinte.164.13.1405}}</ref> However, the table at right shows that in the factorial study, the hallucinations were associated with the absence of chlordiazepoxide and not the presence of propanolol. The combination of both propanolol and chlordiazepoxide gave the best combination of reduction in withdrawal symptoms and arrhythmias.<ref name="pmid7004240"/>
A factorial [[randomized controlled trial]]<ref name="pmid7004240">{{cite journal |author=Zilm DH, Jacob MS, MacLeod SM, Sellers EM, Ti TY |title=Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal |journal=Alcohol. Clin. Exp. Res. |volume=4 |issue=4 |pages=400-5 |year=1980 |pmid=7004240 |doi= |issn=}}</ref> has been misinterpreted leading to concerns that beta-blockers are associated with hallucinations.<ref name="pmid15249349">{{cite journal |author=Mayo-Smith MF, Beecher LH, Fischer TL, ''et al'' |title=Management of alcohol withdrawal delirium. An evidence-based practice guideline |journal=Arch. Intern. Med. |volume=164 |issue=13 |pages=1405-12 |year=2004 |pmid=15249349 |doi=10.1001/archinte.164.13.1405}}</ref> However, the table at right shows that in the factorial study, the hallucinations were associated with the absence of chlordiazepoxide and not the presence of propanolol. The combination of both propanolol and chlordiazepoxide gave the best combination of reduction in withdrawal symptoms and arrhythmias.<ref name="pmid7004240"/>


A case report shows that beta-blockers may remove signs of hyperactivity of the [[sympathetic nervous system]] thus leading to overlooking a diagnosis of delirium tremens in a chronic alcholic with hallucinations after stopping alcohol.<ref name="pmid6122874">{{cite journal |author=Zechnich RJ |title=Beta blockers can obscure diagnosis of delirium tremens |journal=Lancet |volume=1 |issue=8280 |pages=1071-2 |year=1982 |pmid=6122874 |doi= |issn=}}</ref> Thus clinicians should not require the presence of [[sympathetic nervous system|sympathetic]] hyperactivity in diagnosing delirium tremens in a patient receiving beta-blockers.
A case report shows that [[adrenergic beta-antagonist]]s may remove signs of hyperactivity of the [[sympathetic nervous system]] thus leading to overlooking a diagnosis of [[delirium tremens]] in a chronic alcholic with hallucinations after stopping alcohol.<ref name="pmid6122874">{{cite journal |author=Zechnich RJ |title=Beta blockers can obscure diagnosis of delirium tremens |journal=Lancet |volume=1 |issue=8280 |pages=1071-2 |year=1982 |pmid=6122874 |doi= |issn=}}</ref> Thus clinicians should not require the presence of [[sympathetic nervous system|sympathetic]] hyperactivity in diagnosing delirium tremens in a patient receiving beta-blockers.
 
In the two trials of the central alpha-2 adrenergic agonist clonidine, oral clonidine at 0.2 mg three times a day showed benefit<ref name="pmid3300587">{{cite journal |author=Baumgartner GR, Rowen RC |title=Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome |journal=Arch. Intern. Med. |volume=147 |issue=7 |pages=1223-6 |year=1987 |pmid=3300587 |doi=}}</ref>, whereas a trial of intravenous clonidine titrated to stop [[sympathetic nervous system|sympathetic]] symptoms, had cases of hallucinations and bradycardia<ref name="pmid8625628">{{cite journal |author=Spies CD, Dubisz N, Neumann T, ''et al'' |title=Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial |journal=Crit. Care Med. |volume=24 |issue=3 |pages=414–22 |year=1996 |month=March |pmid=8625628 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=24&issue=3&spage=414 |issn=}}</ref>.


===Carbamazepine===
===Carbamazepine===

Revision as of 22:46, 15 January 2009

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Template:TOC-right Alcohol withdrawal is a group of syndromes that may occur after cessation of drinking ethanol alcohol.[1][2][3]

Classification

Autonomic hyperactivity

Withdrawal may cause hyperactivity of the sympathetic nervous system.

Seizures

Alcohol withdrawal seizures is a "condition where seizures occur in association with ethanol abuse (alcoholism) without other identifiable causes. Seizures usually occur within the first 6-48 hours after the cessation of alcohol intake, but may occur during periods of alcohol intoxication. Single generalized tonic-clonic motor seizures are the most common subtype, however, status epilepticus may occur".[4][5]

Delirium

Alcohol withdrawal delirium,formerly called delerium tremens, is an "acute organic mental disorder induced by cessation or reduction in chronic alcohol consumption. Clinical characteristics include confusion; delusions; vivid hallucinations; tremor; agitation; insomnia; and signs of autonomic hyperactivity (e.g., elevated blood pressure and heart rate, dilated pupils, and diaphoresis). This condition may occasionally be fatal."[6][7]

Treatment

Systematic reviews of the treatment of alcohol withdrawal by the Cochrane Collaboration
Intervention Relative risk ratio
Benzodiazepines[8] 0.16
Anticonvulsants[9] 0.57

Benzodiazepines

Benzodiazepines such as diazepam (Valium), lorazepam (Ativan) or oxazepam (Serax) are the most commonly used drugs used to reduce alcohol withdrawal symptoms. There are several treatment patterns in which it is used.

  1. One option takes into consideration the varying degrees of tolerance. In it, a standard dose of the benzodiazepine is given every half hour until light sedation is reached. Once a baseline dose is determined, the medication is tapered over the ensuing 3-10 days.
  2. Another option is to defer treatment until symptoms occur.[10][11] A non-randomized, before and after, observational study found that symptom triggered therapy was advantageous.[12]

Dosing of the benzodiazepines can be guided by the CIWA-Ar scale.[13] The scale is available online (see external links below).

Regarding the choice of benzodiazepine:

  • Chlordiazepoxide (Librium®) is the benzodiazepine of choice in uncomplicated alcohol withdrawal. [14]
  • Lorazepam or diazepam are available parenterally for patients who cannot safely take medications by mouth.
  • Lorazepam and oxazepam may be best in patients with cirrhosis (shorter half life).

Adrenergic antagonists

Number of treatment failures due to severe hallucinations or alcohol withdrawal.
Chlordiazepoxide
Given Not given
Propranolol Given 1 4
Not given 0 4
Notes:
1. There were 15 patients in each group.

2. Not shown is the arrhythmia scores,
which were best in the groups receiving propanolol.

Randomized controlled trials have found benefit from sympatholytics such as atenolol[15], propanolol[16][17] and clonidine.[18][19] In the major trial, atenolol was given to patients without contraindications at a dose of 50 mg if the pulse was 50-79 and 100 mg if the pulse was 80 or more.[15] Clonidine was administered to patients without contraindications as 0.2 mg per dose with the schedule of day 1 at 9pm; day 2 at 9am, 1pm, and 6pm; day 3 9am and 6pm; and day 4 at 9am.[18]

A factorial randomized controlled trial[16] has been misinterpreted leading to concerns that beta-blockers are associated with hallucinations.[1] However, the table at right shows that in the factorial study, the hallucinations were associated with the absence of chlordiazepoxide and not the presence of propanolol. The combination of both propanolol and chlordiazepoxide gave the best combination of reduction in withdrawal symptoms and arrhythmias.[16]

A case report shows that adrenergic beta-antagonists may remove signs of hyperactivity of the sympathetic nervous system thus leading to overlooking a diagnosis of delirium tremens in a chronic alcholic with hallucinations after stopping alcohol.[20] Thus clinicians should not require the presence of sympathetic hyperactivity in diagnosing delirium tremens in a patient receiving beta-blockers.

In the two trials of the central alpha-2 adrenergic agonist clonidine, oral clonidine at 0.2 mg three times a day showed benefit[18], whereas a trial of intravenous clonidine titrated to stop sympathetic symptoms, had cases of hallucinations and bradycardia[19].

Carbamazepine

A randomized controlled trial has found benefit from carbamazepine.[21]

Other drugs

Sodium oxybate is the sodium salt of gamma-hydroxybutyric acid (GHB). It has been studied for both acute alcohol withdrawal[22] and medium to long-term detoxification[23]. This drug enhances neurotransmission by the inhibitory neurotransmitter gamma aminobutyric acid (GABA) and reduces levels of the excitatory neurotransmitter glutamate.

Baclofen has been shown in animal studies and in small human studies to enhance detoxification[24] and maybe reduce craving[25]. This drug acts as a GABA B receptor agonist.

Some hospitals administer alcohol[26] to prevent alcohol withdrawal although this may[27] or may not[28] help.

References

  1. ↑ 1.0 1.1 Mayo-Smith MF, Beecher LH, Fischer TL, et al (2004). "Management of alcohol withdrawal delirium. An evidence-based practice guideline". Arch. Intern. Med. 164 (13): 1405-12. DOI:10.1001/archinte.164.13.1405. PMID 15249349. Research Blogging.
  2. ↑ Mayo-Smith MF, Beecher LH, Fischer TL, Gorelick DA, Guillaume JL, Hill A, Jara G, Kasser C, Melbourne J. (2004). Management of alcohol withdrawal delirium. An evidence-based practice guideline. (English). National Guidelines Clearinghouse. Retrieved on 2008-04-03.
  3. ↑ Mayo-Smith MF (1997). "Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal". JAMA 278 (2): 144-51. PMID 9214531. [e] Full text at OVID
  4. ↑ Anonymous (2024), Alcohol withdrawal seizures (English). Medical Subject Headings. U.S. National Library of Medicine.
  5. ↑ Ropper, Allan H.; Adams, Raymond Delacy; Victor, Maurice (1997). Principles of Neurology (in English), 6th. New York: McGraw-Hill, Health Professions Division, 1174. ISBN 0-07-067439-6. 
  6. ↑ Anonymous (2024), Alcohol withdrawal delirium (English). Medical Subject Headings. U.S. National Library of Medicine.
  7. ↑ Ropper, Allan H.; Adams, Raymond Delacy; Victor, Maurice (1997). Principles of Neurology. New York: McGraw-Hill, Health Professions Division, 1175. ISBN 0-07-067439-6. 
  8. ↑ Ntais C, Pakos E, Kyzas P, Ioannidis JP (2005). "Benzodiazepines for alcohol withdrawal". Cochrane Database Syst Rev (3): CD005063. DOI:10.1002/14651858.CD005063.pub2. PMID 16034964. Research Blogging.
  9. ↑ Polycarpou A, Papanikolaou P, Ioannidis JP, Contopoulos-Ioannidis DG (2005). "Anticonvulsants for alcohol withdrawal". Cochrane Database Syst Rev (3): CD005064. DOI:10.1002/14651858.CD005064.pub2. PMID 16034965. Research Blogging.
  10. ↑ Saitz R, Mayo-Smith MF, Roberts MS, Redmond HA, Bernard DR, Calkins DR (1994). "Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial". JAMA 272 (7): 519-23. PMID 8046805. [e]
  11. ↑ Daeppen JB, Gache P, Landry U, et al (2002). "Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial". Arch. Intern. Med. 162 (10): 1117-21. PMID 12020181. [e]
  12. ↑ Jaeger TM, Lohr RH, Pankratz VS (2001). "Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients". Mayo Clin. Proc. 76 (7): 695-701. PMID 11444401. [e]
  13. ↑ Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM (1989). "Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar)". British journal of addiction 84 (11): 1353-7. PMID 2597811. [e]
  14. ↑ Raistrick, D, Heather N & Godfrey C (2006) "Review of the Effectiveness of Treatment for Alcohol Problems" National Treatment Agency for Substance Misuse, London
  15. ↑ 15.0 15.1 Kraus ML, Gottlieb LD, Horwitz RI, Anscher M (1985). "Randomized clinical trial of atenolol in patients with alcohol withdrawal". N. Engl. J. Med. 313 (15): 905-9. PMID 2863754. [e]
  16. ↑ 16.0 16.1 16.2 Zilm DH, Jacob MS, MacLeod SM, Sellers EM, Ti TY (1980). "Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal". Alcohol. Clin. Exp. Res. 4 (4): 400-5. PMID 7004240. [e]
  17. ↑ Sellers EM, Zilm DH, Degani NC (November 1977). "Comparative efficacy of propranolol and chlordiazepoxide in alcohol withdrawal". J. Stud. Alcohol 38 (11): 2096–108. PMID 592834. [e]
  18. ↑ 18.0 18.1 18.2 Baumgartner GR, Rowen RC (1987). "Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome". Arch. Intern. Med. 147 (7): 1223-6. PMID 3300587. [e]
  19. ↑ 19.0 19.1 Spies CD, Dubisz N, Neumann T, et al (March 1996). "Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial". Crit. Care Med. 24 (3): 414–22. PMID 8625628. [e]
  20. ↑ Zechnich RJ (1982). "Beta blockers can obscure diagnosis of delirium tremens". Lancet 1 (8280): 1071-2. PMID 6122874. [e]
  21. ↑ Malcolm R, Ballenger JC, Sturgis ET, Anton R (1989). "Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal". The American journal of psychiatry 146 (5): 617-21. PMID 2653057. [e]
  22. ↑ Nava F, Premi S, Manzato E, Campagnola W, Lucchini A, Gessa GL (2007). "Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam". Am J Drug Alcohol Abuse 33 (3): 379-92. DOI:10.1080/00952990701315046. PMID 17613965. Research Blogging.
  23. ↑ Caputo F, Addolorato G, Stoppo M, et al (2007). "Comparing and combining gamma-hydroxybutyric acid (GHB) and naltrexone in maintaining abstinence from alcohol: an open randomised comparative study". Eur Neuropsychopharmacol 17 (12): 781-9. DOI:10.1016/j.euroneuro.2007.04.008. PMID 17611081. Research Blogging.
  24. ↑ Addolorato G, Caputo F, Capristo E, et al (2002). "Rapid suppression of alcohol withdrawal syndrome by baclofen". Am. J. Med. 112 (3): 226-9. PMID 11893350. [e]
  25. ↑ Addolorato G, Caputo F, Capristo E, et al (2002). "Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study". Alcohol Alcohol. 37 (5): 504-8. PMID 12217947. [e]
  26. ↑ Blondell RD, Dodds HN, Blondell MN, et al (2003). "Ethanol in formularies of US teaching hospitals". JAMA 289 (5): 552. PMID 12578486. [e]
  27. ↑ Dissanaike S, Halldorsson A, Frezza EE, Griswold J (August 2006). "An ethanol protocol to prevent alcohol withdrawal syndrome". J. Am. Coll. Surg. 203 (2): 186–91. DOI:10.1016/j.jamcollsurg.2006.04.025. PMID 16864031. Research Blogging.
  28. ↑ Weinberg JA, Magnotti LJ, Fischer PE, et al (January 2008). "Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial". J Trauma 64 (1): 99–104. DOI:10.1097/TA.0b013e31815eb12a. PMID 18188105. Research Blogging.

External links

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