What are signs and symptoms of alcohol withdrawal

What is alcohol withdrawal ?

Prolonged alcohol consumption leads to the development of tolerance and physical dependence, which may result from compensatory functional changes in the same ion channels. Abrupt cessation of prolonged alcohol consumption unmasks these changes, leading to the alcohol withdrawal syndrome, which includes blackouts, tremors, muscular rigidity, delirium tremens, and seizures ¹. Alcohol withdrawal syndrome is a distressing and life-threatening medical emergency condition associated with high mortality rates that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption ², ³. The most common effects include shaking, restlessness, difficulty sleeping, nightmares, sweats, high heart rate, fever, feeling sick, vomiting, fits, hallucinations, increased agitation, tremulousness, and delirium. In severe cases, people may lose consciousness, their heart may stop, and they may die ². It is estimated that 2 million Americans experience the symptoms of alcohol withdrawal each year ⁴.

The neurobiological mechanisms underlying alcohol withdrawal syndrome are complex. Alcohol is a central nervous system (CNS) depressant, influencing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Ordinarily, the excitatory (glutamate) and inhibitory (GABA) neurotransmitters are in a state of homeostasis ⁵. Alcohol facilitates GABA action, causing decreased CNS excitability. In the long-term, it causes a decrease in the number of GABA receptors (down regulation). This results in the requirement of increasingly larger doses of ethanol to achieve the same euphoric effect, a phenomenon known as tolerance ⁵. Alcohol acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, thereby reducing the CNS excitatory tone. Chronic use of alcohol leads to an increase in the number of NMDA receptors (up regulation) and production of more glutamate to maintain CNS homeostasis ⁵. Whether these abnormalities represent a trait- or state-dependent marker of ethanol dependence remains to be resolved ⁶.

With the sudden cessation of alcohol in the chronic user, the alcohol mediated central nervous system (CNS) inhibition is reduced and the glutamate mediated CNS excitation is left unopposed, resulting in a net CNS excitation. This CNS excitation results in the clinical symptoms of alcohol withdrawal in the form of autonomic over activity such as tachycardia, tremors, sweating and neuropsychiatric complications such as delirium and seizures ⁷.

Dopamine is another neurotransmitter involved in alcohol withdrawal states. During alcohol use and withdrawal the increase in CNS dopamine levels contribute to the clinical manifestations of autonomic hyper arousal and hallucinations ⁵.

Repeated episodes of withdrawal and neuroexcitation results in a lowered seizure threshold as a result of kindling predisposing to withdrawal seizures ⁸.

Currently, benzodiazepines are the drugs of choice for the treatment of alcohol withdrawal syndrome. These compounds potentiate GABA-A receptor signaling and act to counterbalance the hyperexcitation produced by excessive glutamate transmission. However, benzodiazepine treatment of alcohol withdrawal syndrome has substantial drawbacks, including its own host of rebound effects upon cessation of treatment and increased risk of relapse into alcohol dependence following its withdrawal. Other non-benzodiazepine compounds such as carbamazepine, gabapentin, valproic acid, topiramate, gamma-hydroxybutyric acid, baclofen, and flumazenil have been studied, but have been associated with limited clinical efficacy.

Alcohol abuse and dependence can cause serious health problems as well as interpersonal, social, interpersonal and legal consequences. Dependence on alcohol is evident by reduced control over drinking, tolerance to alcohol and withdrawal symptoms. Excessive drinking, binge drinking, and alcohol dependence were most common among men and those aged 18 to 24. Binge drinking was most common among those with annual family incomes of $75,000 or more, whereas alcohol dependence was most common among those with annual family incomes of less than $25,000 ⁹. The prevalence of alcohol dependence was 10.2% among excessive drinkers, 10.5% among binge drinkers, and 1.3% among non-binge drinkers. A positive relationship was found between alcohol dependence and binge drinking frequency.

Excessive alcohol consumption is responsible for 88,000 deaths annually and cost the United States $223.5 billion in 2006 ⁹. Half of these deaths and three-quarters of the economic costs are due to binge drinking (ie, ≥4 drinks for women and ≥5 drinks for men in a single occasion) ¹⁰. Binge drinking is also associated with a myriad of health and social problems (eg, violence, new HIV infections, unintended pregnancies, and alcohol dependence) ¹¹, ¹².

It is often assumed that most excessive drinkers are alcohol dependent. Because binge drinkers are at higher risk than non-binge drinkers for alcohol dependence ¹³ and about 18 million adult Americans have an alcohol use disorder ¹⁴. Alcohol use disorder is when your drinking causes serious problems in your life, yet you keep drinking. You may also need more and more alcohol to feel drunk. Stopping suddenly may cause withdrawal symptoms. This means that your drinking causes distress and harm. It includes alcoholism and alcohol abuse.

The clinical diagnosis of alcohol dependence is based on criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, and involves the assessment of warning signs such as tolerance, withdrawal, impaired control, and unsuccessful attempts to cut down ¹⁵.

• Heavy drinking was defined as 8 or more drinks per week during the past 30 days for women or 15 or more drinks per week for men ⁹.
• Alcohol dependence or alcoholism, is a disease that causes: 1) Craving – a strong need to drink;  2) Loss of control – not being able to stop drinking once you’ve started; 3) Physical dependence – withdrawal symptoms; 4) Tolerance – the need to drink more alcohol to feel the same effect ¹⁴.

This study ¹⁶ found that about 9 of 10 adult excessive drinkers did not meet the diagnostic criteria for alcohol dependence. About 90% of the adults who drank excessively reported binge drinking, and the prevalence of alcohol dependence was similar among excessive drinkers and binge drinkers across most sociodemographic groups ¹⁶. The prevalence of alcohol dependence also increased with the frequency of binge drinking. However, even among those who reported binge drinking 10 or more times in the past month, more than two-thirds did not meet diagnostic criteria for alcohol dependence according to their responses to the survey ¹⁶.

Too much alcohol is dangerous. Heavy drinking can increase the risk of certain cancers. It can cause damage to the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the risk of death from car crashes, injuries, homicide, and suicide.

If you want to stop drinking, there is help. Start by talking to your health care provider. Treatment may include medicines, counseling, and support groups.

If you cannot stop drinking, GET HELP. There are programs that can help you stop drinking. They are called alcohol treatment programs. Your doctor or nurse can find a program to help you. Even if you have been through a treatment program before, try it again. There are also programs just for women.

Consider joining Alcoholics Anonymous or another mutual support group (see links below). Recovering people who attend groups regularly do better than those who do not. Groups can vary widely, so shop around for one that’s comfortable. You’ll get more out of it if you become actively involved by having a sponsor and reaching out to other members for assistance.

• Alcoholics Anonymous ¹⁷
• Moderation Management ¹⁸
• Secular Organizations for Sobriety ¹⁹
• SMART Recovery ²⁰
• Women for Sobriety ²¹
• Al-Anon Family Groups ²²
• Adult Children of Alcoholics ²³
• National Council on Alcoholism and Drug Dependence ²⁴
• National Institute on Alcohol Abuse and Alcoholism ²⁵
• National Organization on Fetal Alcohol Syndrome ²⁶
• Substance Abuse and Mental Health Services Administration ²⁷

What causes Alcohol use disorder

No one knows what causes problems with alcohol. Health experts think that it may be a combination of a person’s:

• Genes
• Environment
• Psychology, such as being impulsive or having low self-esteem

Depression and anxiety often go hand in hand with heavy drinking. Studies show that people who are alcohol dependent are two to three times as likely to suffer from major depression or anxiety over their lifetime. When addressing drinking problems, it’s important to also seek treatment for any accompanying medical and mental health issues.

Drinking an excessive amount of alcohol can put you at risk for alcohol-related problems if:

• You are a man who has 15 or more drinks a week, or often have 5 or more drinks at a time
• You are a woman who has 8 or more drinks a week, or often have 4 or more drinks at a time.

One drink is defined as 12 ounces or 360 milliliters (mL) of beer (5% alcohol content), 5 ounces or 150 mL of wine (12% alcohol content), or a 1.5-ounce or 45-mL shot of liquor (80-proof, or 40% alcohol content).

If you have a parent with alcohol use disorder, you are more at risk for alcohol problems.

You also may be more likely to have problems with alcohol if you:

• Are a young adult under peer pressure
• Have depression, bipolar disorder, anxiety disorders, or schizophrenia
• Can easily obtain alcohol
• Have low self-esteem
• Have problems with relationships
• Live a stressful lifestyle

If you are concerned about your drinking, it may help to take a careful look at your alcohol use.

Symptoms of Alcohol Use Disorder

Doctors have developed a list of symptoms that a person has to have in the past year to be diagnosed with alcohol use disorder.

To assess whether you or loved one may have Alcohol Use Disorder, here are some questions to ask. In the past year, have you:

• Had times when you ended up drinking more, or longer than you intended?
• More than once wanted to cut down or stop drinking, or tried to, but couldn’t?
• Spent a lot of time drinking? Or being sick or getting over the aftereffects?
• Experienced craving — a strong need, or urge, to drink?
• Found that drinking — or being sick from drinking — often interfered with taking care of your home or family? Or caused job troubles? Or school problems?
• Continued to drink even though it was causing trouble with your family or friends?
• Given up or cut back on activities that were important or interesting to you, or gave you pleasure, in order to drink?
• More than once gotten into situations while or after drinking that increased your chances of getting hurt (such as driving, swimming, using machinery, walking in a dangerous area, or having unsafe sex)?
• Continued to drink even though it was making you feel depressed or anxious or adding to another health problem? Or after having had a memory blackout?
• Had to drink much more than you once did to get the effect you want? Or found that your usual number of drinks had much less effect than before?
• Found that when the effects of alcohol were wearing off, you had withdrawal symptoms, such as trouble sleeping, shakiness, irritability, anxiety, depression, restlessness, nausea, or sweating? Or sensed things that were not there?

If you have any of these symptoms, your drinking may already be a cause for concern. The more symptoms you have, the more urgent the need for change. A health professional can conduct a formal assessment of your symptoms to see if alcohol use disorder is present.

However severe the problem may seem, most people with alcohol use disorder can benefit from treatment. Unfortunately, less than 10 percent of them receive any treatment.

Ultimately, receiving treatment can improve an individual’s chances of success in overcoming alcohol use disorder.

Talk with your doctor to determine the best course of action for you.

Figure 1. Alcohol Use Disorder: American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders Definition

[Source ²⁸]

Exams and Tests for Alcohol use disorder

Your health care provider will:

• Examine you
• Ask about your medical and family history
• Ask about your alcohol use, and if you have any of the symptoms listed above

Your healthcare provider may order tests to check for health problems that are common in people who use alcohol. These tests may include:

• Blood alcohol level (this shows if you have recently been drinking alcohol. It does not diagnose alcohol use disorder.)
• Complete blood count
• Liver function tests
• Magnesium blood test
• Thiamin blood level

Treatment of Alcohol use disorder

Many people with an alcohol problem need to completely stop using alcohol. This is called abstinence. Having strong social and family support can help make it easier to quit drinking.

Some people are able to just cut back on their drinking. So even if you do not give up alcohol altogether, you may be able to drink less. This can improve your health and relationships with others. It can also help you perform better at work or school.

However, many people who drink too much find they can’t just cut back. Abstinence may be the only way to manage a drinking problem.

The good news is that no matter how severe the problem may seem, most people with an alcohol use disorder can benefit from some form of treatment.

Research shows that about one-third of people who are treated for alcohol problems have no further symptoms 1 year later. Many others substantially reduce their drinking and report fewer alcohol-related problems.

Ultimately, there is no one-size-fits-all solution, and what may work for one person may not be a good fit for someone else. Simply understanding the different options can be an important first step.

• Behavioral treatments. Often known as alcohol counseling or “talk therapy,” behavioral treatments also work well. Several counseling approaches are about equally effective—cognitive-behavioral, motivational enhancement, marital and family counseling, or a combination.
• Specialized, intensive treatment programs.Some people will need more intensive programs.

DECIDING TO QUIT

Like many people with an alcohol problem, you may not recognize that your drinking has gotten out of hand. An important first step is to be aware of how much you drink. It also helps to understand the health risks of alcohol.

If you decide to quit drinking, talk with your provider. Treatment involves helping you realize how much your alcohol use is harming your life and the lives those around you.

Depending on how much and how long you have been drinking, you may be at risk for alcohol withdrawal. Withdrawal can be very uncomfortable and even life threatening. If you have been drinking a lot, you should cut back or stop drinking only under the care of a doctor. Talk with your provider about how to stop using alcohol.

LONG-TERM SUPPORT

Alcohol recovery or support programs can help you stop drinking completely. These programs usually offer:

• Education about alcohol use and its effects
• Counseling and therapy to discuss how to control your thoughts and behaviors
• Physical health care

For the best chance of success, you should live with people who support your efforts to avoid alcohol. Some programs offer housing options for people with alcohol problems. Depending on your needs and the programs that are available:

• You may be treated in a special recovery center (inpatient)
• You may attend a program while you live at home (outpatient)

You may be prescribed medicines to help you quit. They are often used with long-term counseling or support groups. These medicines make it less likely that you will drink again or help limit the amount you drink.

Drinking may mask depression or other mood or anxiety disorders. If you have a mood disorder, it may become more noticeable when you stop drinking. Your provider will treat any mental disorders in addition to your alcohol treatment.

Support Groups for Alcohol use disorder

Because an alcohol use disorder can be a chronic relapsing disease, persistence is key. It is rare that someone would go to treatment once and then never drink again. More often, people must repeatedly try to quit or cut back, experience recurrences, learn from them, and then keep trying. For many, continued followup with a treatment provider is critical to overcoming problem drinking. Support groups help many people who are dealing with alcohol use and relapses.

Relapse is common among people who overcome alcohol problems. People with drinking problems are most likely to relapse during periods of stress or when exposed to people or places associated with past drinking.

Just as some people with diabetes or asthma may have flare-ups of their disease, a relapse to drinking can be seen as a temporary set-back to full recovery and not a complete failure. Seeking professional help can prevent relapse — behavioral therapies can help people develop skills to avoid and overcome triggers, such as stress, that might lead to drinking. Most people benefit from regular checkups with a treatment provider. Medications also can deter drinking during times when individuals may be at greater risk of relapse (e.g., divorce, death of a family member).

If you cannot stop drinking, GET HELP. You may have a disease called alcoholism. There are programs that can help you stop drinking. They are called alcohol treatment programs. Your doctor or nurse can find a program to help you. Even if you have been through a treatment program before, try it again. There are also programs just for women.

Consider joining Alcoholics Anonymous or another mutual support group (see links below). Recovering people who attend groups regularly do better than those who do not. Groups can vary widely, so shop around for one that’s comfortable. You’ll get more out of it if you become actively involved by having a sponsor and reaching out to other members for assistance.

• Alcoholics Anonymous ¹⁷
• Moderation Management ¹⁸
• Secular Organizations for Sobriety ¹⁹
• SMART Recovery ²⁰
• Women for Sobriety ²¹
• Al-Anon Family Groups ²²
• Adult Children of Alcoholics ²³
• National Council on Alcoholism and Drug Dependence ²⁴
• National Institute on Alcohol Abuse and Alcoholism ²⁵
• National Organization on Fetal Alcohol Syndrome ²⁶
• Substance Abuse and Mental Health Services Administration ²⁷

FDA-Approved Medications to help people stop or reduce their drinking and avoid relapse

The U.S. Food and Drug Administration (FDA) has approved three medications for treating alcohol dependence, and others are being tested to determine if they are effective ²⁹.

1. Naltrexone can help people reduce heavy drinking.
2. Acamprosate makes it easier to maintain abstinence.
3. Disulfiram blocks the breakdown (metabolism) of alcohol by the body, causing unpleasant symptoms such as nausea and flushing of the skin. Those unpleasant effects can help some people avoid drinking while taking disulfiram.

It is important to remember that not all people will respond to medications, but for a subset of individuals, they can be an important tool in overcoming alcohol dependence.

Of the FDA approved medications, the two newer ones (naltrexone and acamprosate) can make it easier to quit drinking by offsetting changes in the brain caused by alcoholism. They don’t make you sick if you do drink, unlike the older approved medication (disulfiram) ³⁰.

• None of these medications is addictive. They can be combined with mutual-support groups or behavioral treatments.

Naltrexone

Naltrexone blocks opioid receptors that are involved in the rewarding effects of drinking and the craving for alcohol ³¹. It has been shown to reduce relapse to problem drinking in some patients. An extended release version, Vivitrol—administered once a month by injection—is also FDA-approved for treating alcoholism, and may offer benefits regarding compliance.

Acamprosate

Acamprosate (Campral®) acts on the gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems and is thought to reduce symptoms of protracted withdrawal, such as insomnia, anxiety, restlessness, and dysphoria ³¹. Acamprosate has been shown to help dependent drinkers maintain abstinence for several weeks to months, and it may be more effective in patients with severe dependence.

Disulfiram

Disulfiram (Antabuse®) interferes with degradation of alcohol, resulting in the accumulation of acetaldehyde, which, in turn, produces a very unpleasant reaction that includes flushing, nausea, and plapitations if a person drinks alcohol ³¹. The utility and effectiveness of disulfiram are considered limited because compliance is generally poor. However, among patients who are highly motivated, disulfiram can be effective, and some patients use it episodically for high-risk situations, such as social occasions where alcohol is present. It can also be administered in a monitored fashion, such as in a clinic or by a spouse, improving its efficacy.

Scientists are working to develop a larger menu of pharmaceutical treatments that could be tailored to individual needs. As more medications become available, people may be able to try multiple medications to find which they respond to best.

Certain medications already approved for other uses have shown promise for treating alcohol dependence and problem drinking:

• The anti-smoking drug varenicline (marketed under the name Chantix) significantly reduced alcohol consumption and craving among people with alcoholism.
• Gabapentin, a medication used to treat pain conditions and epilepsy, was shown to increase abstinence and reduce heavy drinking. Those taking the medication also reported fewer alcohol cravings and improved mood and sleep.
• The anti-epileptic medication topiramate was shown to help people curb problem drinking, particularly among those with a certain genetic makeup that appears to be linked to the treatment’s effectiveness.

Topiramate

Topiramate is thought to work by increasing inhibitory (GABA) neurotransmission and reducing stimulatory (glutamate) neurotransmission, although its precise mechanism of action is not known ³¹. Although topiramate has not yet received FDA approval for treating alcohol addiction, it is sometimes used off-label for this purpose. Topiramate has been shown in studies to significantly improve multiple drinking outcomes, compared with a placebo.

“Isn’t taking medications just trading one addiction for another?”

This is not an uncommon concern, but the short answer is “no.” All medications approved for treating alcohol dependence are non-addictive ²⁹. These medicines are designed to help manage a chronic disease, just as someone might take drugs to keep their cholesterol or diabetes in check.

Outlook (Prognosis) for Alcohol use disorder

How well a person does depends on whether they can successfully cut back or stop drinking.

It may take several tries to stop drinking for good. If you are struggling to quit, do not give up hope. Getting treatment, if needed, along with support and encouragement from support groups and those around you can help you remain sober.

Possible Complications for Alcohol use disorder

Alcohol use disorder can increase your risk of many health problems, including:

• Bleeding in the digestive tract
• Brain cell damage
• A brain disorder called Wernicke-Korsakoff syndrome
• Cancer of the esophagus, liver, colon, breast and other areas
• Changes in the menstrual cycle
• Delirium tremens (DTs)
• Dementia and memory loss
• Depression and suicide
• Erectile dysfunction
• Heart damage
• High blood pressure
• Inflammation of the pancreas (pancreatitis)
• Liver disease, including cirrhosis
• Nerve damage
• Poor nutrition
• Sleeping problems (insomnia)
• Sexually transmitted infections (STIs)

Alcohol use also increases your risk for violence.

Drinking alcohol while you are pregnant can lead to severe birth defects in the baby. This is called fetal alcohol syndrome.

Prevention for Alcohol use disorder

The National Institute on Alcohol Abuse and Alcoholism recommends:

• Women should not drink more than 1 drink per day
• Men should not drink more than 2 drinks per day

What are the signs and symptoms of alcohol withdrawal

The spectrum of alcohol withdrawal symptoms ranges from such minor symptoms as insomnia and tremulousness to severe complications such as withdrawal seizures and delirium tremens.

[Source ³³]

Table 2. Diagnostic Criteria for Alcohol Withdrawal Symptoms

A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged.
B. Two (or more) of the following, developing within several hours to a few days after criterion A:
	1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 beats per minute)
	2. Increased hand tremor
	3. Insomnia
	4. Nausea or vomiting
	5. Transient visual, tactile, or auditory hallucination s or illusions
	6. Psychomotor agitation
	7. Anxiety
	8. Grand mal seizures
C. The symptoms in criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

[Source ³²]

Table 3. Timing of Alcohol Withdrawal Symptoms Appearance

Symptoms	Time of appearance after cessation of alcohol use
Minor withdrawal symptoms: insomnia, tremulousness, mildanxiety, gastrointestinal upset, headache, diaphoresis, palpitations, anorexia	6 to 12 hours
Alcoholic hallucinosis: visual, auditory, or tactile hallucinations	12 to 24 hours*
Withdrawal seizures: generalized tonic-clonic seizures	24 to 48 hours†
Alcohol withdrawal delirium (delirium tremens): hallucinations (predominately visual), disorientation, tachycardia, hypertension, low-grade fever, agitation, diaphoresis	48 to 72 hours‡

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Table 4. Duration of Alcohol Withdrawal Syndrome

Drug	Peak period	Duration	Signs	Symptoms
Alcohol	1 to 3 days	5 to 7 days	Elevated blood pressure, pulse and temperature, hyperarousal, agitation, restlessness, cutaneous flushing, tremors, diaphoresis, dilated pupils, ataxia, clouding of consciousness, disorientation	Anxiety, panic, paranoid delusions, illusions, visual and auditory hallucinations (often derogatory and intimidating)
Benzodiazepines and other sedative/hypnotics	Short-acting: 2 to 4 days Long-acting: 4 to 7 days	Short-acting: 4 to 7 days Long-acting: 7 to 14 days	Increased psychomotor activity, agitation, muscular weakness, tremulousness, hyperpyrexia, diaphoresis, delirium, convulsions, elevated blood pressure, pulse and temperature, tremor of eyelids, tongue and hands	Anxiety, depression, euphoria, incoherent thoughts, hostility, grandiosity, disorientation, tactile, auditory and visual hallucinations, suicidal thoughts
Stimulants (cocaine, amphetamines and derivatives)	1 to 3 days	5 to 7 days	Social withdrawal, psychomotor retardation, hypersomnia, hyperphagia	Depression, anhedonia, suicidal thoughts and behavior, paranoid delusions
Opiates (heroin)	1 to 3 days	5 to 7 days	Drug seeking, mydriasis, piloerection, diaphoresis, rhinorrhea, lacrimation, diarrhea, insomnia, elevated blood pressure and pulse (mild)	Intense desire for drugs, muscle cramps, arthralgia, anxiety, nausea, vomiting, malaise
PCP/psychedelics	Days to weeks	Days to weeks	Hyperactivity, increased pain threshold, nystagmus, hyperreflexia, hypertension and tachycardia, eyelid retraction (stare), agitation and hyperarousal, dry and erythematous skin, violent and self-destructive behaviors	Anxiety, depression, delusions, auditory and visual hallucinations, memory loss, irritable and angry mood and affect, suicidal thoughts

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[Source ⁴¹]

Figure 2. Graph depicting the time course of alcohol withdrawal symptoms

[Source ⁴²] [Source ⁴⁵]

Note: Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores of 8 points or fewer correspond to mild withdrawal, scores of 9 to 15 points correspond to moderate withdrawal, and scores of greater than 15 points correspond to severe withdrawal symptoms and an increased risk of delirium tremens and seizures.

Figure 4. Clinical descriptions of alcohol withdrawal syndromes by severity

[Source ⁴¹]

What is delirium tremens ?

Delirium tremens is a severe form of alcohol withdrawal. It involves sudden and severe mental or nervous system changes ⁴⁶.

Causes of delirium tremens

Delirium tremens can occur when you stop drinking alcohol after a period of heavy drinking, especially if you do not eat enough food.

Delirium tremens may also be caused by head injury, infection, or illness in people with a history of heavy alcohol use.

It occurs most often in people who have a history of alcohol withdrawal. It is especially common in those who drink 4 to 5 pints (1.8 to 2.4 liters) of wine, 7 to 8 pints (3.3 to 3.8 liters) of beer, or 1 pint (1/2 liter) of “hard” alcohol every day for several months. Delirium tremens also commonly affects people who have used alcohol for more than 10 years.

Symptoms of delirium tremens

Symptoms most often occur within 48 to 96 hours after the last drink. But, they can occur 7 to 10 days after the last drink.

Symptoms may get worse quickly, and can include:

• Delirium, which is sudden severe confusion
• Body tremors
• Changes in mental function
• Agitation, irritability
• Deep sleep that lasts for a day or longer
• Excitement or fear
• Hallucinations (seeing or feeling things that are not really there)
• Bursts of energy
• Quick mood changes
• Restlessness, excitement
• Sensitivity to light, sound, touch
• Stupor, sleepiness, fatigue

Seizures (may occur without other symptoms of delirium tremens):

• Most common in the first 12 to 48 hours after the last drink
• Most common in people with past complications from alcohol withdrawal
• Usually generalized tonic-clonic seizures

Symptoms of alcohol withdrawal, including:

• Anxiety, depression
• Fatigue
• Headache
• Insomnia (difficulty falling and staying asleep)
• Irritability or excitability
• Loss of appetite
• Nausea, vomiting
• Nervousness, jumpiness, shakiness, palpitations (sensation of feeling the heart beat)
• Pale skin
• Rapid emotional changes
• Sweating, especially on the palms of the hands or the face

Other symptoms that may occur:

• Chest pain
• Fever
• Stomach pain

Treatment of Delirium Tremens

The goals of treatment are to:

• Save the person’s life
• Relieve symptoms
• Prevent complications

A hospital stay is needed. The health care team will regularly check:

• Blood chemistry results, such as electrolyte levels
• Body fluid levels
• Vital signs (temperature, pulse, breathing rate, blood pressure)

While in the hospital, the person will receive medicines to:

• Stay calm and relaxed (sedated) until the delirium tremens are finished
• Treat seizures, anxiety, or tremors
• Treat mental disorders, if any

Long-term preventive treatment should begin after the person recovers from delirium tremens symptoms. This may involve:

• A “drying out” period, in which no alcohol is allowed
• Total and lifelong avoidance of alcohol (abstinence)
• Counseling
• Going to support groups (such as Alcoholics Anonymous)

Treatment may be needed for other medical problems that can occur with alcohol use, including:

• Alcoholic cardiomyopathy
• Alcoholic liver disease
• Alcoholic neuropathy
• Wernicke-Korsakoff syndrome.

Outlook (Prognosis) for Delirium tremens

Delirium tremens is serious and may be life threatening. Some symptoms related to alcohol withdrawal may last for a year or more, including:

• Emotional mood swings
• Feeling tired
• Sleeplessness

Possible Complications of Delirium tremens

Complications can include:

• Injury from falls during seizures
• Injury to self or others caused by mental state (confusion/delirium)
• Irregular heartbeat, may be life threatening
• Seizures

Alcohol withdrawal treatment

Regimens used to treat alcohol withdrawal syndrome have evolved over time, taking advantage of advances in the understanding of addiction neurophysiology. There is no specific ethanol receptor ⁴⁷. Much of alcohol’s acute effects on the central nervous system are mediated by its stimulation of the gamma‐aminobutyric acid (GABA) system, which is neuroinhibitory ⁴⁸. Chronic alcohol use leads to habituation partly by inducing configuration changes of GABA‐A receptor subunits. This renders the GABA‐A receptor less sensitive to alcohol, barbiturates, and benzodiazepines ⁴⁹. Although both GABA‐A and GABA‐B receptor activation cause increased GABA neuronal output, the GABA‐A receptor is rendered relatively less sensitive by chronic exposure to alcohol.

Currently, alcohol withdrawal syndrome is usually managed with benzodiazepines, using variable dosing depending on the severity of withdrawal symptoms. Such symptom‐triggered treatment is generally preferred over fixed‐dose regimens ⁵⁰, in part because when using this method, many cases of alcohol withdrawal syndrome can be managed with less medication. Benzodiazepine regimens using high doses have been found to be associated with substantial morbidity and prolonged hospitalizations ⁵¹, ⁵².

Benzodiazepines are the drugs of choice for the treatment of alcohol withdrawal syndrome ⁵³ because these compounds potentiate GABA-A receptor signaling and act to counterbalance the hyperexcitation produced by excessive glutamate transmission. Benzodiazepines showed a protective benefit against seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with antipsychotics ⁵³. Although benzodiazepines are protective in some animal models of alcohol withdrawal seizures ⁵⁴, they do not exhibit high potency. Moreover, benzodiazepine treatment of alcohol withdrawal syndrome has substantial drawbacks, including its own host of rebound effects upon cessation of treatment and increased risk of relapse into alcohol dependence following its withdrawal ⁵⁵.

Nevertheless, clinical experience demonstrates that benzodiazepines do reduce the risk of recurrent seizures in patients with an alcohol withdrawal seizure ³⁸, so that in practice, no complete benzodiazepine resistance occurs. However, GABAA-receptor modulators, other than benzodiazepines, might be superior therapeutic agents. Chlormethiazole is a positive modulator of GABAA receptors, which has high efficacy in enhancing GABAA receptors containing α4 subunits ⁵⁶ and has been shown to protect transiently against alcohol withdrawal seizures in mice withdrawn from exposure to inhaled ethanol ⁵⁷. Although chlormethiazole may be a preferred agent from a theoretical point of view, it is not currently registered for sale in the United States. Other non-benzodiazepine compounds such as carbamazepine, gabapentin, valproic acid, topiramate, gamma-hydroxybutyric acid, baclofen, and flumazenil have been studied, but have been associated with limited clinical efficacy ⁵⁸.

Goals of Treatment

The American Society of Addiction Medicine ³⁴ lists three immediate goals for detoxification of alcohol and other substances:

1. To provide a safe withdrawal from the drug(s) of dependence and enable the patient to become drug-free;
2. To provide a withdrawal that is humane and thus protects the patient’s dignity; and
3. To prepare the patient for ongoing treatment of his or her dependence on alcohol or other drugs.

General Care

Abnormalities in fluid levels, electrolyte levels, or nutrition should be corrected. Intravenous fluids may be necessary in patients with severe withdrawal because of excessive fluid loss through hyperthermia, sweating, and vomiting. Intravenous fluids should not be administered routinely in patients with less severe withdrawal, because these patients may become overhydrated.

Routine administration of magnesium sulfate has not been shown to improve withdrawal symptoms ⁵⁹, but supplementation is appropriate if a patient is hypomagnesemic.

Wernicke’s Encephalopathy results from cell damage due to chronic thiamine deficiency. Wernicke’s Encephalopathy has an associated mortality of 20%, with 75% developing a permanent severe amnestic syndrome (Korsokoff’s encephalopathy) ⁶⁰. This can be prevented by administering parenteral (intravenous) thiamine which achieves adequate blood thiamine level much earlier than the oral route. Allergic reactions are rare. All patients in alcohol withdrawal should receive at least 250 mg thiamine by the parenteral route once a day for the first 3-5 days ⁶¹, whereas for those with suspected Wernicke’s Encephalopathy, thiamine 500 mg/day for 3-5 days is advised. If there is clinical improvement the supplementation is continued for total of 2 weeks.[39] Concurrent administration of parenteral thiamine with glucose is advised traditionally. However, this is only to ensure that thiamine supplementation is not forgotten. Administration of glucose containing fluids before thiamine may not precipitate Wernicke’s Encephalopathy ⁶². Due to chronic malnutrition and gastric malabsorption that follows chronic alcohol abuse, many clinicians advise multivitamin supplements (B1 + B2 + B6 + nicotinamide + Vitamin C) in parenteral form for the initial 3-5 days ⁶³.

Chronic alcohol use is associated with abnormal magnesium metabolism. Those with neuropathy and presenting with severe withdrawal symptoms are more likely to show low serum magnesium level ⁶⁴. Oral or parenteral magnesium supplementation may benefit such patients by reducing the severity and duration of alcohol withdrawal. Routine use is not advised ⁶⁵

Choice of Treatment Setting

In most patients with mild to moderate withdrawal symptoms, outpatient detoxification is safe and effective, and costs less than inpatient treatment ⁶⁶, ⁶⁷, ⁶⁸, ⁶⁹. However, certain patients should be considered for inpatient treatment regardless of the severity of their symptoms. Relative indications for inpatient alcohol detoxification are as follows: history of severe withdrawal symptoms, history of withdrawal seizures or delirium tremens, multiple previous detoxifications, concomitant psychiatric or medical illness, recent high levels of alcohol consumption, pregnancy, and lack of a reliable support network ⁷⁰.

If outpatient treatment is chosen, the patient should be assessed daily. The patient and support person(s) should be instructed about how to take the withdrawal medication, the side effects of the medication, the expected withdrawal symptoms, and what to do if symptoms worsen ³⁴, ⁷¹. Small quantities of the withdrawal medication should be prescribed at each visit; thiamine and a multivitamin also should be prescribed. Because close monitoring is not available in ambulatory treatment, a fixed-schedule regimen should be used.

Alcohol withdrawal medication

Medication can be administered using fixed-schedule or symptom-triggered regimens (Table 2) ⁷². With a fixed-schedule regimen, doses of a benzodiazepine are administered at specific intervals, and additional doses of the medication are given as needed based on the severity of the withdrawal symptoms. In a symptom-triggered regimen, medication is given only when the Clinical Institute Withdrawal Assessment for Alcohol score is higher than 8 points.

Benzodiazepines

Pharmacologic treatment of alcohol withdrawal syndrome involves the use of medications that are cross-tolerant with alcohol. Benzodiazepines have been shown to be safe and effective, particularly for preventing or treating seizures and delirium, and are the preferred agents for treating the symptoms of alcohol withdrawal syndrome ⁷².

The choice of agent is based on pharmacokinetics.

• Diazepam (Valium) and chlordiazepoxide (Librium) are long-acting agents that have been shown to be excellent in treating alcohol withdrawal symptoms. Because of the long half-life of these medications, withdrawal is smoother, and rebound withdrawal symptoms are less likely to occur.

• Lorazepam (Ativan) and oxazepam (Serax) are intermediate-acting medications with excellent records of efficacy. Treatment with these agents may be preferable in patients who metabolize medications less effectively, particularly the elderly and those with liver failure. Lorazepam is the only benzodiazepine with predictable intramuscular absorption (if intramuscular administration is necessary).

Rarely, it is necessary to use extremely high dosages of benzodiazepines to control the symptoms of alcohol withdrawal. Dosages of diazepam as high as 2,000 mg per day have been administered ⁷³. Because clinicians often are reluctant to administer exceptionally high dosages, under-treatment of alcohol withdrawal is a common problem.

One randomized controlled trial ⁷⁴ affirmed previous findings that carbamazepine is an effective alternative to benzodiazepines in the treatment of alcohol withdrawal syndrome in patients with mild to moderate symptoms. Patients in the study received 800 mg of carbamazepine on the first day, with the dosage tapered to 200 mg by the fifth day. Carbamazepine (Tegretol) also appears to decrease the craving for alcohol after withdrawal. It is not sedating and has little potential for abuse. Although carbamazepine is used extensively in Europe, its use in the United States has been limited by lack of sufficient evidence that it prevents seizures and delirium.

Several medications have shown early promise in the treatment of alcohol withdrawal. Gabapentin, which is structurally similar to GABA, has been effective in the treatment of alcohol withdrawal in small studies ⁷⁵, ⁷⁶. The low toxicity of gabapentin makes it a promising agent. In another study ⁷⁷, the anticonvulsant agent vigabatrin, which irreversibly blocks GABA transaminase, improved withdrawal symptoms after only three days of treatment.

Vigabatrin, an anticonvulsant agent, which irreversibly blocks GABA transaminase, showed improvement in withdrawal symptoms after only three days of treatment and is a promising agent for detoxification ⁷⁸.

Valproic acid significantly affects the course of alcohol withdrawal and reduces the need for treatment with a benzodiazepine ⁷⁹. These two double-blind ⁷⁹, ⁸⁰, randomized studies showed that patients treated with Valproic acid for 4 to 7 days dropped out less frequently, had less severe withdrawal symptoms including fewer seizures, and required less oxazepam than patients receiving either carbamazepine or placebo. Although effective, Valproic acid use may be limited by side effects—somnolence, gastrointestinal disturbances, confusion, and tremor—which are similar to alcohol withdrawal symptoms, making assessment of improvement difficult.

Adjunctive Agents

Several medications may be helpful adjuncts to benzodiazepines in the treatment of alcohol withdrawal syndrome. However, these medications should not be used as monotherapy.

• Haloperidol (Haldol) can be used to treat agitation and hallucinations, although it can lower the seizure threshold.
• The use of atenolol (Tenormin) in conjunction with oxazepam has been shown to improve vital signs more quickly and to reduce alcohol craving more effectively than the use of oxazepam alone ⁸¹.

Adjunctive treatment with a beta blocker should be considered in patients with coronary artery disease, who may not tolerate the strain that alcohol withdrawal can place on the cardiovascular system.

• Clonidine (Catapres) also has been shown to improve the autonomic symptoms of withdrawal ⁷².

Although phenytoin (Dilantin) does not treat withdrawal seizures, it is an appropriate adjunct in patients with an underlying seizure disorder.

 

Table 5. Examples of Treatment Regimens for Alcohol Withdrawal

Monitoring (with no medication)
Monitor the patient by administering the CIWA-Ar (see Figure 3. Clinical Institute Withdrawal Assessment for Alcohol) every 4 to 8 hours until the score has been lower than 8 to 10 points for 24 hours.
Perform additional assessments as needed.
Symptom-triggered regimens
Administer the Clinical Institute Withdrawal Assessment for Alcohol every hour to assess the patient’s need for medication.
Administer one of the following medications every hour when the Clinical Institute Withdrawal Assessment for Alcohol score is at least 8 to 10 points:
	Chlordiazepoxide (Librium), 50 to 100 mg
	Diazepam (Valium), 10 to 20 mg
	Lorazepam (Ativan), 2 to 4 mg
Fixed-schedule regimen
Administer one of the following medications every 6 hours:
	Chlordiazepoxide, four doses of 50 mg, then eight doses of 25 mg
	Diazepam, four doses of 10 mg, then eight doses of 5 mg
	Lorazepam, four doses of 2 mg, then eight doses of 1 mg
Provide additional medication as needed when symptoms are not controlled (i.e., the Clinical Institute Withdrawal Assessment for Alcohol score remains at least 8 to 10 points).

[Source ⁸²]

Symptom-triggered regimens have been shown to result in the administration of less total medication and to require a shorter duration of treatment ⁸³, ⁸⁴. In one randomized, double-blind controlled trial ⁸³, patients in the symptom-triggered group received an average of 100 mg of chlordiazepoxide, whereas patients in the fixed-schedule group received an average of 425 mg. The median duration of treatment in the symptom-triggered group was nine hours, compared with 68 hours in the fixed-schedule group. Patients were excluded from the study if they had concurrent medical or psychiatric illness requiring hospitalization or seizures from any cause ⁸³.

Another trial ⁸⁴ yielded similar results, with patients in the fixed-schedule group receiving an average of 231.4 mg of oxazepam and those in the symptom-triggered group receiving an average of 37.5 mg. Of the patients in the symptom-triggered group, 61 percent did not receive any oxazepam. This trial excluded persons with major psychiatric, cognitive, or medical comorbidities.

The use of symptom-triggered therapy requires training of the clinical staff. If this training has not been provided, fixed-schedule pharmacotherapy should be used ⁷².

Patient Follow-Up

Treatment of alcohol withdrawal syndrome should be followed by treatment for alcohol dependence. Treatment of withdrawal alone does not address the underlying disease of addiction and therefore offers little hope for long-term abstinence.

In the outpatient setting, brief interventions are helpful in patients with alcohol abuse ⁸⁵, but more intense interventions are required in patients with alcohol dependence. The anticonvulsant topiramate (Topamax) has been shown to be an effective adjunctive medication to decrease alcohol consumption and increase abstinence in alcohol-dependent patients ⁸⁶.

Some patients achieve dramatic results by joining 12-step groups such as Alcoholics Anonymous and Narcotics Anonymous. Other patients benefit from stays in comprehensive treatment facilities, which offer a combination of a 12-step model, cognitive-behavior therapy, and family therapy. The treatment of alcohol withdrawal syndrome should be supplemented by an individualized, comprehensive treatment program, or at least as many elements of such a program as the patient can tolerate and afford.

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