Alcohol Withdrawal Syndrome

From Wikipedia, the free encyclopedia


Alcohol withdrawal syndrome is the set of symptoms seen when an individual reduces or stops alcohol consumption after prolonged periods of excessive alcohol intake. Excessive abuse of alcohol leads to tolerance, physical dependence, and an alcohol withdrawal syndrome. Unlike most withdrawals from drugs, alcohol withdrawal can be deadly.


Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptions occur such as changes in gene expression and down regulation of GABAa receptors. During acute alcohol withdrawal changes also occur such as upregulation of alpha4 containing GABAa receptors and down regulation of alpha1 and alpha3 containing GABAa receptors. Neurochemical changes occurring during alcohol can be minimised with drugs which are used for acute detoxification. With abstinence from alcohol and cross tolerant drugs these changes in neurochemistry gradually return towards normal.[1][2]


The severity of the alcohol withdrawal syndrome can vary from mild symptoms such as mild sleep disturbances and mild anxiety to very severe and life threatening including delirium, particularly visual hallucinations in severe cases and convulsions (which may result in death).[3] The severity of alcohol withdrawal depends on various factors including age, genetics and most importantly degree of alcohol intake and length of time the individual has been misusing alcohol for and number of previous detoxifications.[4][5]

Withdrawal symptoms

Protracted withdrawal

A protracted alcohol withdrawal syndrome occurs in many alcoholics where withdrawal symptoms continue beyond the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with severity over time. This syndrome is also sometimes referred to as the post acute withdrawal syndrome. Some withdrawal symptoms can linger for at least a year after discontinuation of alcohol. Symptoms can include a craving for alcohol, inability to feel pleasure from normally pleasurable things (also known as anhedonia), clouding of sensorium, disorientation, nausea and vomiting or headache.[14] Insomnia is also a common protracted withdrawal symptom which persists after the acute withdrawal phase of alcohol. Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in alcoholics because many of the traditional sleep aids eg benzodiazepine receptor agonists and barbiturate receptor agonists work via a GABAA receptor mechanism and are cross tolerant with alcohol. However, trazodone is not cross tolerant with alcohol.[15][16][17] The acute phase of the alcohol withdrawal syndrome can also occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal.[18]


Kindling is the phenomenon where repeated alcohol detoxifications leads to an increased severity of the withdrawal syndrome. For example binge drinkers may initially experience no withdrawal symptoms but with each period of resumption of drinking followed by abstinence their withdrawal symptoms intensify in severity and may eventually result in full blown delirium tremens with convulsive seizures. Alcoholics who experience seizures during hospital detoxification have been found to be much more likely to have had experienced more previous detoxifications from alcohol than alcoholics who did not have seizures and are more likely to have a more medically complicated alcohol withdrawal syndrome. Kindling can cause complications and may increase the risk of relapse, alcohol related brain damage and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alerations in the GABA<AA receptors.[19] The mechanism behind kindling is sensitisation of some neuronal systems and desensitisation of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.[5]


Treatment of alcohol withdrawal syndrome can be managed with various pharmaceutical medications including barbiturates, benzodiazepines and clonidine. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome.


Baclofen has been shown to be as effective as diazepam in uncomplicated alcohol withdrawal syndrome.[20]


Barbiturates are superior to diazepam in the treatment of severe alcohol withdrawal syndromes such as delirium tremens but equally effective in milder cases of alcohol withdrawal.[21]


Benzodiazepines are the most commonly used drug for the treatment of alcohol withdrawal and are safe and effective in suppressing alcohol withdrawal signs. Chlordiazepoxide and diazepam are the benzodiazepines most commonly used in alcohol detoxification.[22] Benzodiazepines can be life saving, particularly if delerium tremens appears during alcohol withdrawal.[23] Benzodiazepines should only be used short term in alcoholics who aren't already dependent on benzodiazepines as benzodiazepines share cross tolerance with ethanol and there is a risk of replacing the addiction with a benzodiazepine dependence or worse still adding an additional addiction. Furthermore disrupted GABA benzodiazepine receptor function is part of alcohol dependence and chronic benzodiazepines may prevent full recovery from alcohol induced mental effects.[24][25] Benzodiazepines have the problem of increasing cravings for alcohol in problem alcohol consumers and they also increase the volume of alcohol consumed by problem drinkers.[26] The combindation of benzodiazepines and alcohol can amplify the adverse psychological effects of each other causing enhanced depressive effects on mood and increase suicidal actions and are generally contraindicated except for alcohol withdrawal.[27]


Some evidence indicates that carbamazepine may be effective in the treatment of alcohol withdrawal but more research is needed.[28] It has the advantage of not causing rebound withdrawal symptoms and appears to have a higher success rate compared with lorazepam.[29]


Clonidine has demonstrated superior clinical effects in the suppression of alcohol withdrawal symptoms in a head to head comparison study with the benzodiazepine drug chlordiazepoxide.[30][31][32]


Alcohol (ethanol) itself at low doses has been found to be superior to chlordiazepoxide in the detoxification of alcohol dependent patients. Low dose ethanol as a means of weaning alcoholics off of alcohol was found to produce less profound sleep disturbances during withdrawal.[33] Low dose ethanol has been found to reduce treatment time, improve the failure rate from 20% down to 7% and increase retention in treatment centres with an increased rate of alcoholics attending substance misuse clinics after detoxification.[34]


Flumazenil, which has shown some promise in the management of the benzodiazepine withdrawal syndrome has also demonstrated benefit in a research study in reducing anxiety withdrawal related symptomatology during alcohol withdrawal.[35]


Trazodone has demonstrated efficacy in the treatment of the alcohol withdrawal syndrome. It may have particular use in withdrawal symptoms, especially insomnia, persisting beyond the acute withdrawal phase.[36][16][17]


Alcoholics are often deficient in various nutrients which can cause severe complications during alcohol withdrawal such as the development of wernicke syndrome. The vitamins of most importance in alcohol withdrawal are thiamine and folic acid. To help to prevent wernicke syndrome alcoholics should be administered a multivitamin preparation with sufficient quantities of thiamine and folic acid. Vitamins should always be administered before any glucose is administered otherwise wernicke syndrome can be precipitated.[37]


Smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics.[38]

See also


  1. ^ Sanna, E; Mostallino, Mc; Busonero, F; Talani, G; Tranquilli, S; Mameli, M; Spiga, S; Follesa, P; Biggio, G (December 2003). "Changes in GABA(A) receptor gene expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal". The Journal of neuroscience : the official journal of the Society for Neuroscience 23 (37): 11711–24. ISSN 0270-6474. PMID 14684873. 
  2. ^ Idemudia SO, Bhadra S, Lal H (June 1989). "The pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal is potentiated by bicuculline and picrotoxinin". Neuropsychopharmacology 2 (2): 115–22. PMID 2742726. 
  3. ^ a b c d e f g h i j Harada K (1993). "[Emotional condition in alcohol withdrawal acute psychosis]". Seishin Shinkeigaku Zasshi 95 (7): 523–9. PMID 8234534. 
  4. ^ Liskow BI; Rinck C, Campbell J, DeSouza C (September 1989). "Alcohol withdrawal in the elderly". J Stud Alcohol 50 (5): 414–21. PMID 2779242. 
  5. ^ a b Howard C. Becker (1998). "Kindling in Alcohol Withdrawal" (PDF). Alcohol Health & Research World (NIAAA) 22 (1). 
  6. ^ a b c d e f g h i j k l m n o Bayard M, McIntyre J, Hill KR, Woodside J (March 2004). "Alcohol withdrawal syndrome". Am Fam Physician 69 (6): 1443–50. PMID 15053409. 
  7. ^ Cowley DS (January 24, 1992). "Alcohol abuse, substance abuse, and panic disorder". Am J Med 92 (1A): 41S–48S. doi:10.1016/0002-9343(92)90136-Y. PMID 1346485. 
  8. ^ Muralidharan K; Rajkumar RP, Ananthapadmanabha Rao S, Benegal V (2007). "Catatonia as a presenting feature of alcohol withdrawal: a case report". Prim Care Companion J Clin Psychiatry 9 (6): 465. PMID 18185829. 
  9. ^ Burov YV; Treskov VG, Vedernikova NN, Shevelyova OS (May 1986). "Types of alcohol withdrawal syndrome and dexamethasone suppression test". Drug Alcohol Depend 17 (1): 81–8. doi:10.1016/0376-8716(86)90039-6. PMID 3720534. 
  10. ^ Abitan J; Sigrist O (8-15). "[Treatment of alcohol withdrawal symptoms: a clinical study (author's transl)]". Sem Hop 55 (21-22): 1105–7. PMID 225818. 
  11. ^ Peppers MP (Jan-Feb 1996). "Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease". Pharmacotherapy: 49–57. 
  12. ^ Fruensgaard K (February 1976). "Withdrawal psychosis: a study of 30 consecutive cases". Acta Psychiatr Scand 53 (2): 105–18. PMID 3091. 
  13. ^ Gann H; Feige B, Hohagen F, van Calker D, Geiss D, Dieter R (September 1, 2001). "Sleep and the cholinergic rapid eye movement sleep induction test in patients with primary alcohol dependence". Biol Psychiatry 50 (5): 383–90. doi:10.1016/S0006-3223(01)01172-6. PMID 11543743. 
  14. ^ Martinotti G; Nicola MD, Reina D, Andreoli S, Focà F, Cunniff A, Tonioni F, Bria P, Janiri L (2008). "Alcohol protracted withdrawal syndrome: the role of anhedonia". Subst Use Misuse 43 (3-4): 271–84. doi:10.1080/10826080701202429. PMID 18365930. 
  15. ^ Hornyak M; Haas P, Veit J, Gann H, Riemann D (November 2004). "Magnesium treatment of primary alcohol-dependent patients during subacute withdrawal: an open pilot study with polysomnography". Alcohol Clin Exp Res 28 (11): 1702–9. doi:10.1097/01.ALC.0000145695.52747.BE. PMID 15547457. 
  16. ^ a b Le Bon O; Murphy JR, Staner L, Hoffmann G, Kormoss N, Kentos M, Dupont P, Lion K, Pelc I, Verbanck P (August 2003). "Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations". J Clin Psychopharmacol 23 (4): 377–83. doi:10.1097/ PMID 12920414. 
  17. ^ a b Borras L; de Timary P, Constant EL, Huguelet P, Eytan A (November 2006). "Successful treatment of alcohol withdrawal with trazodone". Pharmacopsychiatry 39 (6): 232. doi:10.1055/s-2006-951385. PMID 17124647. 
  18. ^ Miller FT (Mar-Apr 1994). "Protracted alcohol withdrawal delirium". J Subst Abuse Treat 11 (2): 127–30. doi:10.1016/0740-5472(94)90029-9. PMID 8040915. 
  19. ^ Malcolm RJ (2003). "GABA systems, benzodiazepines, and substance dependence". J Clin Psychiatry 64 Suppl 3: 36–40. PMID 12662132. 
  20. ^ Addolorato G; Leggio L, Abenavoli L, Agabio R, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G (March 2006). "Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam". Am J Med 119 (3): 276.e13–8. doi:10.1016/j.amjmed.2005.08.042. PMID 16490478. 
  21. ^ Kramp P; Rafaelsen OJ (August 1978). "Delirium tremens: a double-blind comparison of diazepam and barbital treatment". Acta Psychiatr Scand 58 (2): 174–90. doi:10.1111/j.1600-0447.1978.tb06930.x. PMID 358756. 
  22. ^ Ebell MH (April 1, 2006). Benzodiazepines for alcohol withdrawal. 73. pp. 1191. PMID 16623205. 
  23. ^ Wolf KM, Shaughnessy AF, Middleton DB (1993). "Prolonged delirium tremens requiring massive doses of medication". J Am Board Fam Pract 6 (5): 502–4. PMID 8213241. 
  24. ^ Toki S, Saito T, Nabeshima A, Hatta S, Watanabe M, Takahata N (February 1996). "Changes in GABAA receptor function and cross-tolerance to ethanol in diazepam-dependent rats". Alcohol. Clin. Exp. Res. 20 (1 Suppl): 40A–44A. PMID 8659687. 
  25. ^ Rassnick S, Krechman J, Koob GF (April 1993). "Chronic ethanol produces a decreased sensitivity to the response-disruptive effects of GABA receptor complex antagonists". Pharmacol. Biochem. Behav. 44 (4): 943–50. PMID 8385785. 
  26. ^ Poulos CX, Zack M (November 2004). "Low-dose diazepam primes motivation for alcohol and alcohol-related semantic networks in problem drinkers". Behav Pharmacol 15 (7): 503–12. PMID 15472572. 
  27. ^ Ziegler PP (August 2007). "Alcohol use and anxiety". Am J Psychiatry 164 (8): 1270; author reply 1270–1. doi:10.1176/appi.ajp.2007.07020291. PMID 17671296. 
  28. ^ Prince V; Turpin KR (June 1, 2008). "Treatment of alcohol withdrawal syndrome with carbamazepine, gabapentin, and nitrous oxide". Am J Health Syst Pharm 65 (11): 1039–47. doi:10.2146/ajhp070284. PMID 18499876. 
  29. ^ Malcolm R; Myrick H, Roberts J, Wang W, Anton RF, Ballenger JC (May 2002). "The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial". J Gen Intern Med 17 (5): 349–55. doi:10.1046/j.1525-1497.2002.10201.x. PMID 12047731. 
  30. ^ Baumgartner GR (January 1988). "Clonidine versus chlordiazepoxide in acute alcohol withdrawal: a preliminary report". South Med J 81 (1): 56–60. doi:10.1097/00007611-198801000-00012. PMID 3276009. 
  31. ^ Baumgartner GR; Rowen RC (July 1987). "Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome". Arch Intern Med 147 (7): 1223–6. doi:10.1001/archinte.147.7.1223. PMID 3300587. 
  32. ^ Björkqvist SE (October 1975). "Clonidine in alcohol withdrawal". Acta Psychiatr Scand 52 (4): 256–63. doi:10.1111/j.1600-0447.1975.tb00041.x. PMID 1103576. 
  33. ^ Funderburk FR; Allen RP, Wagman AM (March 1978). "Residual effects of ethanol and chlordiazepoxide treatments for alcohol withdrawal". J Nerv Ment Dis 166 (3): 195–203. PMID 205633. 
  34. ^ 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. 
  35. ^ Little HJ (July 1991). "The benzodiazepines: anxiolytic and withdrawal effects". Neuropeptides 19 Suppl: 11–4. PMID 1679209. 
  36. ^ Roccatagliata G; Albano C, Maffini M, Farelli S (1980). "Alcohol withdrawal syndrome: treatment with trazodone". Int Pharmacopsychiatry. 15 (2): 105–10. PMID 6108298. 
  37. ^ Hugh Myrick; Raymond F Anton (1998). "Treatment of Alcohol Withdrawal" (PDF). Alcohol Health & Research World (niaaa) 22 (1). 
  38. ^ Durazzo TC, Meyerhoff DJ (2007). "Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism". Front. Biosci. 12: 4079–100. PMID 17485360.


Faith (for Content):