Alcohol withdrawal syndrome

Alcohol withdrawal syndrome is the set of symptoms seen when an individual reduces or stops alcohol consumption after prolonged period of excessive alcohol intake. Excessive misuse of alcohol leads to tolerance, physical dependence and an alcohol withdrawal syndrome.

Neurochemistry

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. [ cite journal |pmid=14684873 |url=http://www.jneurosci.org/cgi/content/full/23/37/11711 |year=2003 |month=Dec |author=Sanna, E; Mostallino, Mc; Busonero, F; Talani, G; Tranquilli, S; Mameli, M; Spiga, S; Follesa, P; Biggio, G |title=Changes in GABA(A) receptor gene expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal |volume=23 |issue=37 |pages=11711–24 |issn=0270-6474 |journal=The Journal of neuroscience : the official journal of the Society for Neuroscience ]

Presentation

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).cite journal |author=Harada K |title= [Emotional condition in alcohol withdrawal acute psychosis] |journal=Seishin Shinkeigaku Zasshi |volume=95 |issue=7 |year=1993 |pages=523–9 |pmid=8234534 ] 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. [cite journal |author=Liskow BI |coauthors=Rinck C, Campbell J, DeSouza C |title=Alcohol withdrawal in the elderly |journal=J Stud Alcohol |volume=50 |issue=5 |year=1989 |month=Sep |pages=414–21 |pmid=2779242 ] cite journal |author=Howard C. Becker | publisher = NIAAA |title=Kindling in Alcohol Withdrawal |journal=Alcohol Health & Research World |volume=22 |issue=1 |year=1998 |url=http://pubs.niaaa.nih.gov/publications/arh22-1/25-34.pdf |format=PDF]

Withdrawal symptoms

*Agitation
*Alcoholic hallucinosis
*Anorexiacite journal |author=MAX BAYARD |coauthors=JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Anxiety and panic attacks [cite journal |author=Cowley DS |coauthors= |journal=Am J Med |title=Alcohol abuse, substance abuse, and panic disorder |year=1992 |month=Jan |date=24 |pages=41S–48S|volume=92 |issue=1A |pmid=1346485 |doi=10.1016/0002-9343(92)90136-Y]
*Catatonia [cite journal |author=Muralidharan K |coauthors=Rajkumar RP, Ananthapadmanabha Rao S, Benegal V |journal=Prim Care Companion J Clin Psychiatry |title=Catatonia as a presenting feature of alcohol withdrawal: a case report |year=2007 |volume=9 |issue=6 |pages=465 |publisher=pubmed |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18185829 |pmid=18185829]
*Confusion
*Delirium tremens
*Depression [cite journal |author=Burov YV |coauthors=Treskov VG, Vedernikova NN, Shevelyova OS |journal=Drug Alcohol Depend |title=Types of alcohol withdrawal syndrome and dexamethasone suppression test |year=1986 |month=May |volume=17 |issue=1 |pages=81–8 |pmid=3720534 |doi=10.1016/0376-8716(86)90039-6 ] [cite journal |author=Abitan J |coauthors=Sigrist O |journal=Sem Hop |title= [Treatment of alcohol withdrawal symptoms: a clinical study (author's transl)] |year=1979 |month=Jun |date=8-15 |volume=55 |issue=21-22 |pages=1105–7 |pmid=225818 ]
*Diaphoresiscite journal |author=MAX BAYARD |coauthors= JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Diarrhea
*Euphoria
*Fear
*Gastrointestinal upsetcite journal |author=MAX BAYARD |coauthors= JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Hallucinations
*Headachecite journal |author=MAX BAYARD |coauthors= JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Hypertension
*Insomniacite journal |author=MAX BAYARD |coauthors= JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Irritability
*Nausea and vomitingcite journal |author=Peppers MP |journal=Pharmacotherapy |title=Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease |year=1996 |month=Jan-Feb |pages=49–57 ]
*Palpitationscite journal |author=MAX BAYARD |coauthors= JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Psychosis
*Rebound REM sleep [cite journal |author=Gann H |coauthors=Feige B, Hohagen F, van Calker D, Geiss D, Dieter R |journal=Biol Psychiatry |title=Sleep and the cholinergic rapid eye movement sleep induction test in patients with primary alcohol dependence |year=2001 |month=Sep |date=1 |pages=383–90|volume=50 |issue=5 |pmid=11543743 |doi=10.1016/S0006-3223(01)01172-6]
*Palpitationscite journal |author=MAX BAYARD |coauthors= JONAH MCINTYRE, KEITH R. HILL, JACK WOODSIDE JR | publisher=aafp |journal=American Family Physician |title= Alcohol Withdrawal Syndrome |year=2004 |month=Mar |date=15 |url=http://www.aafp.org/afp/20040315/1443.html ]
*Restlessness
*Seizures and death
*Sweating
*Tachycardia
*Tremors
*Weakness

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. [cite journal |author=Martinotti G |coauthors=Nicola MD, Reina D, Andreoli S, Focà F, Cunniff A, Tonioni F, Bria P, Janiri L |journal=Subst Use Misuse |title=Alcohol protracted withdrawal syndrome: the role of anhedonia |year=2008 |volume=43 |issue=3-4 |pages=271–84 |pmid=18365930 |doi=10.1080/10826080701202429 ] 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 GABA_A receptor mechanism and are cross tolerant with alcohol. However, trazodone is not cross tolerant with alcohol. [cite journal |author=Hornyak M |coauthors=Haas P, Veit J, Gann H, Riemann D |journal=Alcohol Clin Exp Res |title=Magnesium treatment of primary alcohol-dependent patients during subacute withdrawal: an open pilot study with polysomnography |year=2004 |month=Nov |volume=28 |issue=11 |pages=1702–9 |pmid=15547457 |doi=10.1097/01.ALC.0000145695.52747.BE ] cite journal |author=Le Bon O |coauthors=Murphy JR, Staner L, Hoffmann G, Kormoss N, Kentos M, Dupont P, Lion K, Pelc I, Verbanck P |title=Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations |journal=J Clin Psychopharmacol |year=2003 |month=Aug |volume=23 |issue=4 |pages=377–83 |pmid=12920414 |doi=10.1097/01.jcp.0000085411.08426.d3] cite journal |author=Borras L |coauthors=de Timary P, Constant EL, Huguelet P, Eytan A |title=Successful treatment of alcohol withdrawal with trazodone |journal=Pharmacopsychiatry |year=2006 |month=Nov |volume=39 |issue=6 |pages=232 |pmid=17124647 |doi=10.1055/s-2006-951385] 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. [cite journal |author=Miller FT |journal=J Subst Abuse Treat |title=Protracted alcohol withdrawal delirium |year=1994 |month=Mar-Apr |volume=11 |issue=2 |pages=127–30 |pmid=8040915 |doi=10.1016/0740-5472(94)90029-9 ]

Kindling

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.The mechanism behind kindling is sensitisation of some neuronal systems and desensitisation of other neuronal system which increasingly leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.cite journal |author=Howard C. Becker | publisher = NIAAA |title=Kindling in Alcohol Withdrawal |journal=Alcohol Health & Research World |volume=22 |issue=1 |year=1998 |url=http://pubs.niaaa.nih.gov/publications/arh22-1/25-34.pdf |format=PDF]

Treatment

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

Baclofen has been shown to be as effective as diazepam in uncomplicated alcohol withdrawal syndrome. [cite journal | author = Addolorato G | coauthors = Leggio L, Abenavoli L, Agabio R, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G | date = | year = 2006 | month = Mar | title = Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam | journal = Am J Med | volume = 119 | issue = 3 | pages = 276.e13–8 | pmid = 16490478 | doi = 10.1016/j.amjmed.2005.08.042 ]

Barbiturates

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. [cite journal |author=Kramp P |coauthors=Rafaelsen OJ |title=Delirium tremens: a double-blind comparison of diazepam and barbital treatment |journal=Acta Psychiatr Scand |volume=58 |issue=2 |pages=174–90 |year=1978 |month=Aug |pmid=358756 |doi=10.1111/j.1600-0447.1978.tb06930.x]

Benzodiazepines

Benzodiazepines are the most commonly used drug for the treatment of alcohol withdrawal and are safe and effective in suppressing alcohol withdrawal signs. [cite journal |author=Ebell MH |title=Benzodiazepines for alcohol withdrawal |journal= |volume=73 |issue=7 |pages=1191 |year=2006 |month=Apr |date=1 |pmid=16623205 |url=http://www.aafp.org/afp/20060401/cochrane.html#c2]

Carbamazepine

Some evidence indicates that carbamazepine may be effective in the treatment of alcohol withdrawal but more research is needed. [cite journal |author=Prince V |coauthors=Turpin KR |title=Treatment of alcohol withdrawal syndrome with carbamazepine, gabapentin, and nitrous oxide |journal=Am J Health Syst Pharm |volume=65 |issue=11 |pages=1039–47 |year=2008 |month=Jun |date=1 |pmid=18499876 |doi=10.2146/ajhp070284] It has the advantage of not causing rebound withdrawal symptoms and appears to have a higher success rate compared with lorazepam. [cite journal | author=Malcolm R | coauthors=Myrick H, Roberts J, Wang W, Anton RF, Ballenger JC | year=2002 | month=May | title=The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial | journal=J Gen Intern Med | volume=17 | issue=5 | pages=349–55 | pmid=12047731 | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12047731 | doi=10.1046/j.1525-1497.2002.10201.x ]

Clonidine

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. [cite journal |author=Baumgartner GR |title=Clonidine versus chlordiazepoxide in acute alcohol withdrawal: a preliminary report |journal=South Med J |volume=81 |issue=1 |pages=56–60 |year=1988 |month=Jan |pmid=3276009 |doi=10.1097/00007611-198801000-00012] [cite journal |author=Baumgartner GR |coauthors=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 |month=Jul |pmid=3300587 |doi=10.1001/archinte.147.7.1223] [cite journal |author=Björkqvist SE |title=Clonidine in alcohol withdrawal |journal=Acta Psychiatr Scand |volume=52 |issue=4 |pages=256–63 |year=1975 |month=Oct |pmid=1103576 |doi=10.1111/j.1600-0447.1975.tb00041.x ]

Ethanol

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. [cite journal |author=Funderburk FR |coauthors=Allen RP, Wagman AM |title=Residual effects of ethanol and chlordiazepoxide treatments for alcohol withdrawal |journal=J Nerv Ment Dis |volume=166 |issue=3 |pages=195–203 |year=1978 |month=Mar |pmid=205633] 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. [cite journal |author=Dissanaike S |coauthors=Halldorsson A, Frezza EE, Griswold J |title=An ethanol protocol to prevent alcohol withdrawal syndrome |journal=J Am Coll Surg |volume=203 |issue=2 |pages=186–91 |year=2006 |month=Aug |pmid=16864031 |doi=10.1016/j.jamcollsurg.2006.04.025 ]

Trazodone

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. [cite journal|author=Roccatagliata G |coauthors=Albano C, Maffini M, Farelli S |title=Alcohol withdrawal syndrome: treatment with trazodone |journal=Int Pharmacopsychiatry. |year=1980 |volume=15 |issue=2 |pages=105–10 |pmid=6108298] cite journal |author=Le Bon O |coauthors=Murphy JR, Staner L, Hoffmann G, Kormoss N, Kentos M, Dupont P, Lion K, Pelc I, Verbanck P |title=Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations |journal=J Clin Psychopharmacol |year=2003 |month=Aug |volume=23 |issue=4 |pages=377–83 |pmid=12920414 |doi=10.1097/01.jcp.0000085411.08426.d3] cite journal |author=Borras L |coauthors=de Timary P, Constant EL, Huguelet P, Eytan A |title=Successful treatment of alcohol withdrawal with trazodone |journal=Pharmacopsychiatry |year=2006 |month=Nov |volume=39 |issue=6 |pages=232 |pmid=17124647 |doi=10.1055/s-2006-951385]

Vitamins

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. [cite journal |author=Hugh Myrick |coauthors=Raymond F Anton |title=Treatment of Alcohol Withdrawal |journal=Alcohol Health & Research World |year=1998 |volume=22 |issue=1 |publisher=niaaa |url=http://pubs.niaaa.nih.gov/publications/arh22-1/38-43.pdf |format=PDF ]

ee also

*Addiction
*Alcoholism
*Benzodiazepine withdrawal syndrome
*Delirium tremens
*Long-term effects of alcohol
*Physical dependence
*Post Acute Withdrawal Syndrome
*Wernicke's encephalopathy
*Wernicke-Korsakoff syndrome

References