Alcohol withdrawal syndrome (AWS) is a spectrum of symptoms that results from abrupt cessation of alcohol in a dependent patient. Symptoms can begin within 5 hours of the last drink and persist for 5–10 days, ranging in severity.
Each year, 8.2 million Americans meet diagnostic criteria for alcohol dependence. It is more prevalent among men, whites, Native Americans, younger and unmarried adults, and those with lower socioeconomic status; only 24% of those with dependence are ever treated. <5% of US adults will experience withdrawal.
- Older age
- High tolerance, prolonged use, high quantities
- Previous alcohol withdrawal episodes, detoxifications, alcohol withdrawal seizures, and delirium tremens (DTs)
- Serious medical problems
- Concomitant benzodiazepine dependence
Geriatric populations dependent on alcohol are more susceptible to symptoms of alcohol withdrawal, and chronic comorbid conditions place them at higher risk of complications from withdrawal.
Hospitalization or inpatient detoxification is usually required for treatment of acute alcohol withdrawal.
There is some evidence for a genetic basis of alcohol dependence.
- Routinely screen all adults for alcohol misuse (1)[B].
- Screen with the CAGE or similar questionnaire:
- Feeling the need to Cut down
- Annoyed by criticism about alcohol use
- Guilt about drinking/behaviors while intoxicated
- "Eye opener” to quell withdrawal symptoms
- Useful to detect problematic alcohol use, positive screen is ≥2 “yes” responses
- 10-question AUDIT screening test is also useful to identify problem drinking.
- The “5 A's” is a screening tool used in primary care settings (Assess, Advise, Agree, Assist, Arrange).
- Consumption of alcohol potentiates the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). With chronic alcohol ingestion, this repeated stimulation down-regulates the inhibitory effects of GABA.
- Concurrently, alcohol ingestion inhibits the stimulatory effect of glutamate on the CNS, with chronic alcohol use up-regulating excitatory NMDA glutamate receptors.
- When alcohol is abruptly stopped, the combined effect of a down-regulated inhibitory neurotransmitter system (GABA-modulated) and up-regulated excitatory neurotransmitter system (glutamate-modulated) results in brain hyperexcitability when no longer suppressed by alcohol; clinically seen as AWS.
Commonly Associated Conditions
- General: Poor nutrition, electrolyte abnormalities (hyponatremia, hypomagnesemia, hypophosphatemia), thiamine deficiency, and dehydration
- GI: Hepatitis, cirrhosis, varices, GI bleed
- Heme: Splenomegaly, thrombocytopenia, macrocytic anemia
- Cardiovascular: Cardiomyopathy, hypertension, atrial fibrillation, other arrhythmias
- CNS: Trauma, seizure disorder, generalized atrophy, Wernicke-Korsakoff syndrome
- Peripheral nervous system (PNS): Neuropathy, myopathy
- Pulmonary: Aspiration pneumonitis or pneumonia; increased risk of anaerobic infections
- Psychiatric: Depression, posttraumatic stress disorder, bipolar disease, polysubstance abuse
- Diagnostic and Statistical Manual of Mental Disorders AWS criteria are diagnosed when ≥2 of the following present within a few hours to several days after the cessation or reduction of heavy and prolonged alcohol ingestion:
- Autonomic hyperactivity (sweating, tachycardia)
- Increased hand tremor
- Psychomotor agitation
- Grand mal seizures
- Transient (visual, auditory, or tactile) hallucinations or illusions
- These should cause clinically significant distress or impair functioning and not be secondary to an underlying medical condition or mental disorder.
- There are 3 stages to AWS:
- Stage 1 (minor withdrawal; onset 5–8 hours after cessation):
- Mild anxiety, restlessness, and agitation
- Mild nausea/GI upset and decreased appetite
- Sleep disturbance
- Mild tremulousness
- Fluctuating tachycardia and hypertension
- Stage 2 (major withdrawal; onset 24–72 hours after cessation):
- Marked restlessness and agitation
- Moderate tremulousness with constant eye movements
- Nausea, vomiting, diarrhea, anorexia
- Marked tachycardia and hypertension
- Alcoholic hallucinosis (auditory, tactile, or visual); may have mild confusion but can be reoriented
- Stage 3 (DTs; onset 72–96 hours after cessation):
- Severe hypertension, tachycardia
- Drenching sweats
- Marked tremors
- Persistent hallucinations
- Stage 1 (minor withdrawal; onset 5–8 hours after cessation):
- Alcohol withdrawal–associated seizures are often brief, generalized tonic-clonic seizures and can occur 6–48 hours after last drink.
Essential historical information should be:
- Duration and quantity of alcohol intake, time since last drink
- Previous episodes/symptoms of alcohol withdrawal, prior detox admissions
- Concurrent substance use
- Pre-existing medical and psychiatric conditions, prior seizure activity
- Social history: Living situation, social support, stressors, triggers, etc.
Should include assessment of conditions likely to complicate or that are exacerbated by AWS:
- Cardiovascular: Arrhythmias, heart failure, coronary artery disease
- GI: GI bleed, liver disease, pancreatitis
- Neuro: Oculomotor dysfunction, gait ataxia, neuropathy
- Psych: Orientation, memory
- General: Hand tremor, infections
Diagnostic Tests and Interpretation
- Blood alcohol level, urine drug screen
- CBC; comprehensive metabolic panel
Initial Imaging Approach
CNS imaging if acute mental status changes
- The goal is to prevent and treat withdrawal symptoms (i.e., seizures, DTs, cardiovascular events). This is done primarily with benzodiazepines (BZDs), which reduce the duration of symptoms and raise the seizure threshold:
- Exclude other medical and psychiatric causes.
- Provide a quiet, protective environment.
- The Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA) is useful for determining medication dosing and frequency of evaluation for AWS. The CIWA scale rates the severity of 10 symptoms on a scale from 1–7, with 1 being without symptoms and 7 being the max score:
- Nausea and vomiting
- Paroxysmal sweats
- Tactile disturbances
- Auditory disturbances
- Visual disturbances
- Headache or fullness in head
- Orientation and clouding of sensorium
- Frequent re-evaluation with CIWA score is crucial.
- BZD monotherapy remains the treatment of choice (3)[A]; it is associated with fewer complications compared with neuroleptics (4)[A].
- BZD should be chosen by the following considerations:
- Agents with rapid onset control agitation more quickly (e.g., IV or PO diazepam [Valium]).
- Long-acting BZDs (diazepam, chlordiazepoxide [Librium]) are more effective at preventing breakthrough seizures and delirium management.
- Short-acting BZDs (lorazepam [Ativan], oxazepam [Serax]) are preferable when prolonged sedation is a concern (e.g., elderly patients or other serious concomitant medical illness) and preferable when severe hepatic insufficiency may impair metabolism (4)[A].
- BZD dosages will vary by patients. Given as symptom-triggered or fixed-schedule regimens. Symptom-triggered regimens have been found to require less BZD amounts and reduce hospitalization time (2)[A].
- Symptom-triggered regimen: Start with chlordiazepoxide 50–100 mg PO, repeat CIWA hourly and if score is ≥8, give additional dose of chlordiazepoxide 50 mg PO. Continue to re-evaluate with CIWA hourly until adequate sedation achieved (score <8). May substitute chlordiazepoxide with respective doses of diazepam, lorazepam, or oxazepam (2)[C].
- β-blockers (e.g., atenolol[Tenormin]) and α2 agonists (e.g., clonidine [Catapres]) help to control hypertension and tachycardia and can be used with BZDs (2)[C]. Not used as monotherapy, due to their inability to prevent DTs and seizures.
- Carbamazepine: Not recommended as first-line therapy; associated with reduced incidence of seizures but more studies are needed (5,3)[C].
- Thiamine: 100 mg daily IV or IM for at least 3 days (4)[C]:
- Note that IV glucose administered before treatment with thiamine may precipitate Wernicke encephalopathy and Korsakoff psychosis.
- If the patient exhibits significant agitation and alcoholic hallucinosis, an antipsychotic (haloperidol [Haldol]) can be used, but this requires close observation as it lowers the seizure threshold (2)[C].
Peripheral neuropathy and cerebellar dysfunction merit physical therapy evaluation.
Patients in withdrawal stages 1 and 2 can be treated as outpatients unless medical comorbidities require inpatient care. A reliable and supportive social environment should be in place with frequent follow-up.Admission Criteria
- CIWA score >15, or severe withdrawal
- Concurrent acute illness requiring in patient care
- Poor ability to follow-up or no reliable social support
- Seizure disorder or history of severe alcohol-related seizures
- Suicide risk
- Concurrent BZD dependence
- Age >40 years old
- Prolonged heavy drinking >8 years
- Consumes >1 pint of alcohol or 12 beers per day
- Random blood alcohol level >200 mg/dL
- Elevated MCV, BUN
- Cirrhosis, liver failure
CIWA scores of <10 on 3 consecutive determinations
- Discharge arrangements include transfer to a treatment facility (i.e., sober house or residential program), outpatient substance abuse counseling, peer support groups (Alcoholics Anonymous), and the use of adjuvant treatment such as disulfiram (Antabuse), acamprosate (Campral), or naltrexone (ReVia, Vivitrol).
- Disulfiram: Irreversibly inhibits aldehyde dehydrogenase, blocking alcohol metabolism, leading to an accumulation of acetaldehyde; therefore, it reinforces the individual's desires to stop drinking by providing a disincentive associated with increase acetaldehyde:
- 250–500 mg/d PO × 1–2 weeks; maintenance 250 mg/d PO
- Contraindications: Concomitant use of metronidazole and ethanol-containing products, psychosis, severe myocardial disease, and coronary occlusion
- Acamprosate (666 mg PO t.i.d.): Glutamate and GABA modulator indicated to reduce cravings:
- Contraindications: Renal impairment (CrCl <30 mL/min)
- Naltrexone (50 mg/d PO; 380 mg IM every 4 weeks): Opiate receptor antagonist, theorized to attenuate pleasurable effects of alcohol and reduce craving. Initiate therapy after patient is opioid-free for at least 7 days:
- Contraindications: Acute hepatitis/liver failure, concomitant opioid therapy
Frequent follow-up to monitor for relapse
Mortality from severe withdrawal (DTs) is 1–5%.
Occurs more frequently in individuals who have prior episodes of withdrawal or concomitant illnesses.
- 291.0 Alcohol withdrawal delirium
- 291.81 Alcohol withdrawal
- 303.90 Other and unspecified alcohol dependence, unspecified drinking behavior
- F10.239 Alcohol dependence with withdrawal, unspecified
- F10.230 Alcohol dependence with withdrawal, uncomplicated
- F10.231 Alcohol dependence with withdrawal delirium
- 191480000 Alcohol withdrawal syndrome (disorder)
- 8635005 alcohol withdrawal delirium (disorder)
- 66590003 Alcohol dependence (disorder)
- The kindling phenomenon has postulated that long-term exposure to alcohol affects neurons, resulting in increased alcohol craving and progressively worse withdrawal episodes.
- The CIWA is a useful tool for managing the symptoms and treatment of alcohol withdrawal.
- Any BZD dose should be patient-specific, sufficient to achieve and maintain a “light somnolence” (e.g., sleeping but easily arousable), and should be tapered off carefully even after AWS resolves.
- Administer thiamine before patient receives glucose, so as not to precipitate Wernicke encephalopathy.
- There should be frequent outpatient follow-up to monitor for relapse.
- Counsel patients taking disulfiram to avoid over-the-counter products that contain alcohol (i.e., mouthwashes).
- Avoid IM diazepam and lorazepam because of erratic absorption.
Molly Hayes, PharmD
Neela Bhajandas, PharmD
Aditi Satti, MD
- Rockville MD. Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse, Topic Page. USPSTF April. 2004.
- Mayo-Smith MF. Pharmacological management of alcohol withdrawal: a meta-analysis and evidence-based practice guideline. JAMA. 1997;278:144–1451. [PMID:9214531]
- Ntais C, Pakos E, Kyzas P, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2005;(3):CD005063. Epub 2005 Jul 20.
- Amato L, Minozzi S, Davoli M, et al. Efficacy and safety of pharmacological interventions for the treatment of the Alcohol Withdrawal Syndrome. Cochrane Database Syst Rev. 2011;(6):CD008537.
- Minozzi S, Amato L, Vecchi S, et al. Anticonvulsants for alcohol withdrawal. Cochrane Database Syst Rev. 2010;(3):CD005064. Epub 2010 Mar 17.
- Sarff M, Gold JA. Alcohol withdrawal syndromes in the intensive care unit. Crit Care Med. 2010;38(9 Suppl):S494–S501. [PMID:20724883]
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