Alcohol withdrawal syndrome - AbsoluteAstronomy.com

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

Post Acute Withdrawal Syndrome

Post-acute-withdrawal syndrome is a set of persistent impairments that occur after withdrawal from alcohol, opiates, benzodiazepines and other substances...

. 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

Anhedonia

In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

), clouding of sensorium

Sensorium

The term sensorium refers to the sum of an organism's perception, the "seat of sensation" where it experiences and interprets the environments within which it lives. The term originally enters English from the Late Latin in the mid-17th century, from the stem sens-...

, disorientation, nausea and vomiting or headache. 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 the persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in alcoholics because many of the traditional sleep aids (e.g. benzodiazepine receptor agonists and barbiturate receptor agonists) work via a GABA_A receptor mechanism and are cross tolerant with alcohol. However, trazodone

Trazodone

Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...

is not cross tolerant with alcohol. The acute phase of the alcohol withdrawal syndrome can also occasionally be protracted. Protracted delirium tremens

Delirium tremens

Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...

has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal.

Pathophysiology

Chronic use of alcohol

Ethanol

Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression

Gene expression

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

and down regulation of GABA_A receptors. During acute alcohol withdrawal, changes also occur such as upregulation of alpha4 containing GABA_A receptors and down regulation of alpha1 and alpha3 containing GABA_A receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross tolerant drugs these changes in neurochemistry gradually return towards normal. Adaptations to the NMDA

NMDA

N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...

system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels which are elevated during chronic drinking increase even further during the withdrawal state and may result in excito-neurotoxicity. Alterations in ECG, in particular an increase in QT interval

QT interval

In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...

, and EEG

EEG

EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...

abnormalities including may occur during early withdrawal.

Kindling

Kindling is the phenomenon where repeated alcohol detoxifications lead 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

Delirium tremens

Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...

with convulsive seizures. Alcoholics who experience seizures during hospital detoxification have been found to be much more likely to have experienced more previous alcohol detoxification episodes than alcoholics who did not have seizures. Those experiencing previous detoxification are more likely to have more medically complicated alcohol withdrawal symptoms. Kindling can cause complications and may increase the risk of relapse, alcohol related brain damage

Brain damage

"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...

and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alterations in the GABA_A receptors.

The mechanism behind kindling is sensitization of some neuronal systems and desensitization of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety

Anxiety

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, convulsions and neurotoxicity

Neurotoxicity

Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

.

Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning

Social emotional learning

Social emotional learning is a process for learning life skills, including how to deal with oneself, others and relationships, and work in an effective manner. In dealing with oneself, SEL helps in recognizing our emotions and learning how to manage those feelings...

. These adverse effects are believed to be due to the neurotoxic effects of repeated withdrawal from alcohol on aberrant neuronal plasticity and cortical damage. Repeated periods of acute intoxication followed by acute detoxification has profound effects on the brain and is associated with an increased risk of seizures as well as cognitive deficits. The effects on the brain are similar to those seen in alcoholics who have been detoxified multiple times but not as severe as in alcoholics who have no history of prior detox. Thus the acute withdrawal syndrome appears to be the most important factor in causing damage or impairment to brain function. The brain regions most sensitive to harm from binge drinking are the amygdala

Amygdala

The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...

and prefrontal cortex

Prefrontal cortex

The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...

.

People in adolescence

Adolescence

Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...

who experience multiple withdrawals from binge drinking

Binge drinking

Binge drinking or heavy episodic drinking is the modern epithet for drinking alcoholic beverages with the primary intention of becoming intoxicated by heavy consumption of alcohol over a short period of time. It is a kind of purposeful drinking style that is popular in several countries worldwide,...

show impairments of long-term nonverbal memory. Alcoholics who have had two or more alcohol withdrawals show more frontal lobe cognitive dysfunction than alcoholics who have experienced one or no prior withdrawals. Kindling of neurons is the proposed cause of withdrawal related cognitive damage. Kindling from multiple withdrawals leads to accumulating neuroadaptational changes. Kindling may also be the reason for cognitive damage seen in binge drinkers.

Diagnosis

Many hospitals use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA

Ciwa

The CIWA is a common measure used in North American hospitals to assess and treat Alcohol withdrawal syndrome and for Alcohol detoxification. This clinical tool assesses 10 common withdrawal signs...

) protocol in order to assess the level of withdrawal present and therefore the amount medication needed. When overuse of alcohol is suspected but drinking history is unclear, testing for elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can help make the diagnosis of alcohol overuse and dependence more clear.

Treatment

Benzodiazepines are effective for the management of symptoms as well as the prevention of seizures.

Treatment of alcohol withdrawal syndrome can be managed with various pharmaceutical medications including barbiturates and clonidine

Clonidine

Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...

. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome.

Benzodiazepines

Benzodiazepines such as diazepam

Diazepam

Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...

or lorazepam

Lorazepam

Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...

, are the most commonly used drug for the treatment of alcohol withdrawal and are generally safe and effective in suppressing alcohol withdrawal signs. Chlordiazepoxide

Chlordiazepoxide

Chlordiazepoxide, is a sedative/hypnotic drug and benzodiazepine. It is marketed under the trade names Angirex, Klopoxid, Librax , Libritabs, Librium, Mesural, Multum, Novapam, Risolid, Silibrin, Sonimen and Tropium.Chlordiazepoxide was the first benzodiazepine to be synthesised and...

and diazepam

Diazepam

are the benzodiazepines most commonly used in alcohol detoxification. Benzodiazepines can be life saving, particularly if delirium tremens

Delirium tremens

Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...

appears during alcohol withdrawal. Benzodiazepines should only be used short term in alcoholics who aren't already dependent on benzodiazepines as benzodiazepines share cross tolerance with ethanol

Alcohol

In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

and there is a risk of replacing the addiction with a benzodiazepine dependence

Benzodiazepine dependence

Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...

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. 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. The combination 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.

Antipsychotics

Antipsychotic agents such as haloperidol

Haloperidol

Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....

are sometimes used for alcohol withdrawal as an add-on to first-line measures such as benzodiazepines to control agitation or psychosis. Antipsychotics may potentially worsen alcohol withdrawal effects (or other CNS depressant withdrawal states) as they lower the seizure threshold and can worsen withdrawal effects. Clozapine

Clozapine

Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...

, olanzapine

Olanzapine

Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...

or low potency phenothiazines (e.g. chlorpromazine

Chlorpromazine

Chlorpromazine is a typical antipsychotic...

) are particularly risky; if used, extreme caution is required. There is also concern for this class of drugs prolonging the QT interval, sometimes leading to fatal heart dysrhthmias.

Anticonvulsants

Some evidence indicates that topiramate

Topiramate

Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...

carbamazepine

Carbamazepine

Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...

and other anticonvulsants are effective in the treatment of alcohol withdrawal however, research is limited. A Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not statistically significant and noted significant weaknesses in the studies available and recommended further research. The Cochrane Review did note however, that paraldehyde

Paraldehyde

Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane. The corresponding tetramer is metaldehyde. A colourless liquid, it is sparingly soluble in water and highly soluble in alcohol. Paraldehyde slowly oxidizes in air, turning brown and producing...

combined with chloral hydrate

Chloral hydrate

Chloral hydrate is a sedative and hypnotic drug as well as a chemical reagent and precursor. The name chloral hydrate indicates that it is formed from chloral by the addition of one molecule of water. Its chemical formula is C2H3Cl3O2....

showed superiority over chlordiazepoxide with regard to incidence of life threatening side effects and also noted that carbamazapine may have advantages for certain symptoms. The advantages of carbamazapine demonstrated in one trial are less rebound withdrawal symptoms and appears to have a higher success rate for abstinence from alcohol post detoxification compared to benzodiazepines.

Baclofen

Baclofen

Baclofen

Baclofen is a derivative of gamma-aminobutyric acid . It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism....

has been shown to be as effective as diazepam

Diazepam

in uncomplicated alcohol withdrawal syndrome.

Barbiturates

Barbiturates are superior to diazepam in the treatment of severe alcohol withdrawal syndromes such as delirium tremens

Delirium tremens

Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...

but equally effective in milder cases of alcohol withdrawal.

Clomethiazole

Clomethiazole

Clomethiazole

Clomethiazole is a sedative and hypnotic originally developed by Hoffmann-Le Roche in the 1930s. The drug is used in treating and preventing symptoms of acute alcohol withdrawal....

(Heminevrin) is a non-benzodiazepine sedative-hypnotic with anticonvulsant effects which is active on the barbiturate site of the GABA-A receptor. Clomethiazole also inhibits the enzyme alcohol dehydrogenase, which is responsible for breaking down alcohol in the body. This slows the rate of elimination of alcohol from the body, which helps to relieve the sudden effects of alcohol withdrawal in alcoholics.

Clonidine

Clonidine

Clonidine

Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...

has demonstrated superior clinical effects in the suppression of alcohol withdrawal symptoms in a head to head comparison study with the benzodiazepine drug chlordiazepoxide

Chlordiazepoxide

.

Ethanol

Alcohol (ethanol

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. Low dose ethanol has been found to reduce treatment time, improve the failure rate from 20% down to 7% and increase retention in treatment centers with an increased rate of alcoholics attending substance misuse clinics after detoxification.

Flumazenil

Flumazenil

Flumazenil

Flumazenil is a benzodiazepine antagonist available for injection only, and the only benzodiazepine receptor antagonist on the market today.It was first introduced in 1987 by Hoffmann-La Roche under the trade name Anexate, but only approved by...

, which has shown some promise in the management of the benzodiazepine withdrawal syndrome

Benzodiazepine withdrawal syndrome

Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...

has also demonstrated benefit in a research study in reducing anxiety

Anxiety

withdrawal related symptomatology during alcohol withdrawal.

Trazodone

Trazodone

Trazodone

Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...

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.

Magnesium

Magnesium appears to be effective in the treatment of alcohol withdrawal related cardiac arrhythmias. It is ineffective in controlling other symptoms of alcohol withdrawal.

Vitamins

The prophylactic administration of thiamine

Thiamine

Thiamine or thiamin or vitamin B1 , named as the "thio-vitamine" is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects if not present in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are...

intravenously is recommended before starting any carbohydrate containing fluids or food. Alcoholics are often deficient in various nutrients which can cause severe complications during alcohol withdrawal such as the development of Wernicke syndrome

Wernicke-Korsakoff syndrome

Wernicke–Korsakoff syndrome is a manifestation of thiamine deficiency, or beriberi. This is usually secondary to alcohol abuse...

. The vitamins of most importance in alcohol withdrawal are thiamine

Thiamine

and folic acid

Folic acid

Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...

. 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.

Prevention of brain damage

It has been proposed that brain damage due to alcohol withdrawal may be prevented by the administration of NMDA antagonists, calcium antagonists, and glucocorticoid antagonists. The NMDA antagonist acamprosate

Acamprosate

Acamprosate, also known as N-acetyl homotaurine and by the brand name Campral, is a drug used for treating alcohol dependence.Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcoholism, possibly by blocking glutamatergic...

reduces excessive glutamate rebound thereby suppressing excitotoxicity and potential withdrawal related neurotoxicity.

Substances impairing recovery

Continued use of benzodiazepines may impair recovery from psychomotor and cognitive impairments from alcohol. Cigarette smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics.

Protracted withdrawal

Pathophysiology

Kindling

Diagnosis

Treatment

Prevention of brain damage

Substances impairing recovery

See also