Alcohol use disorder (AUD) is a leading risk factor for premature death and disability in the US and worldwide.1,2 In the US, nearly 15 million people aged 12 years and older had AUD in 2019 and excessive alcohol use is responsible for approximately 95,000 deaths per year.1,3

Previously described as separate disorders in the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV), the DSM-5 combines symptoms of both alcohol dependence and alcohol abuse into 1 disorder — AUD — and classifies the disorder as mild, moderate, or severe.2,4,5

Providing individualized care to patients with AUD who seek treatment is challenging. Patients with a history of heavy drinking for a prolonged period who significantly reduce their alcohol consumption or abruptly stop drinking can develop alcohol withdrawal syndrome. This typically occurs within 4 to 12 hours of the last drink with symptoms lasting for up to 5 days.2 More than 50% of patients with AUD develop alcohol withdrawal symptoms when discontinuing or decreasing alcohol use.6


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Symptoms of alcohol withdrawal range from anxiety, agitation, tremor, insomnia, nausea, and hallucinations to potentially life-threatening seizures and delirium tremens (DTs; Table 1).2,5-8 In patients with unsuspected or untreated DTs, mortality rates are reported to be up to 37%.6

Pathophysiology of Alcohol Withdrawal Syndrome

The effects of alcohol on the central nervous system are linked to the gamma-aminobutyric acid (GABA)-chloride channel receptor complex.9,10 GABA is the main inhibitory neurotransmitter and glutamate is the primary excitatory neurotransmitter in the brain.10,11 The GABA receptor is a pentameric protein, comprised of 5 subunits – 2 alpha, 2 beta, and 1 gamma (Figure).10 In between the alpha and beta subunits lies the binding site for GABA.9,10 Ethanol readily binds to the receptors on the GABA protein complex because of its high affinity for ethanol.12 As a positive allosteric modulator, alcohol acts as a central nervous system depressant because of its inhibitory effect on N-methyl-D-aspartate (NMDA) receptors leading to sedative and anxiolytic effects.9,11

Alcohol withdrawal causes a significant decrease in GABA levels, which subsequently causes a hyperactive response in the nervous system.11 Withdrawal also causes activation of glutamate, which enhances the function of the NMDA receptors.11,13,14

Detecting Alcohol Withdrawal Syndrome

The American Society of Addiction Medicine (ASAM) recommends universal screening for unhealthy alcohol use in medical settings using validated scales to help identify patients with or at risk for AUD and alcohol withdrawal.8

Some of the screening questionnaires for AUD that can be used in both the inpatient and outpatient setting include the following11,15:

  • Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)
  • Cut-Down, Annoyed, Guilty, and Eye-Opener (CAGE)
  • Munich Alcoholism Test (MALT)

Alcohol dependence should be considered in women who report more than 1 drink daily or more than 7 drinks per week, and in men who average more than 2 drinks daily or more than 14 drinks per week.16,17 Patients’ average daily and/or weekly alcohol intake, history of previous cessation attempts, history of previous alcohol withdrawals, presence of concurrent medical or psychiatric conditions, and concurrent drug abuse should be taken into consideration as clinicians assess for the presence of withdrawal symptoms.17

The Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) is a 10-item assessment tool that can evaluate the presence of withdrawal symptoms, quantify the severity of symptoms, and individualize treatment selection (Table 2).11,18 Each item is evaluated independently, with all components then aggregated to yield a score correlating with the severity of alcohol withdrawal.11 Each component is scored on a scale from 0 to 7, except for orientation and sensorium, which is scored from 0 to 4. In patients who score less than 8, the presence of alcohol withdrawal symptoms is suggested to be absent or minimal. Patients scoring 8 to 20 are noted to be in mild to moderate withdrawal, and those scoring greater than 20 are considered to be experiencing severe withdrawal symptoms. Patients with scores of 10 or less typically do not need pharmacologic treatment.18

Other scales that can be used to assess for the risk for severe alcohol withdrawal include8:

  • Luebeck Alcohol-Withdrawal Risk Scale (LARS)
  • Prediction of Alcohol Withdrawal Severity Scale (PAWSS)

Although data collected from these assessments are extremely helpful in detection of alcohol withdrawal symptoms, the screening tools should be used as supportive measures in combination with the clinical picture as provided by a detailed history and thorough physical examination. Additionally, laboratory investigations such as urine drug screening, liver functions tests, blood alcohol levels, electrolyte levels, and a complete blood count are mainstays for establishing a diagnosis.17

Treatment Setting

The treatment setting is primarily determined by the severity of the withdrawal symptoms present.11 In patients presenting with mild to moderate withdrawal, outpatient detoxification is considered safe and effective.11,17 Although outpatient follow-up recommendations include seeing the patient daily until symptoms subside, treatment in this environment is cost effective, less burdensome on acute care hospitals, and minimizes interruptions on the patient’s personal life.11,17 An inpatient setting is warranted for patients who experience seizures or DTs or have severe withdrawal symptoms, abnormal laboratory results, or chronic medical or psychiatric conditions.8,17

Management of Alcohol Withdrawal Syndrome

Patients at risk of developing alcohol withdrawal syndrome (AWS) may be provided with preventative pharmacotherapy with benzodiazepines when attempting to reduce or stop alcohol intake, according to the 2020 ASAM guidelines on AWS. Benzodiazepines are first-line treatment for AWS prophylaxis because of their effectiveness in reducing the signs and symptoms of withdrawal, such as the incidence of seizure and delirium.8

Mild Symptoms

For patients experiencing mild withdrawal symptoms (eg, CIWA-Ar score <8) who are at minimal risk of developing severe symptoms or complications of alcohol withdrawal, the ASAM recommends treatment with pharmacotherapy or supportive care alone. Carbamazepine or gabapentin are appropriate pharmacologic treatments for mild symptoms. For patients with mild symptoms who are at risk of developing new or worsening withdrawal while away from the treatment setting, the ASAM recommends use of benzodiazepines, carbamazepine, or gabapentin.8

Moderate Symptoms

Patients with moderate symptoms (eg, CIWA-Ar scores 8-20) should be treated with pharmacotherapy with benzodiazepines being the first-line treatment; carbamazepine or gabapentin are appropriate alternative therapies. Benzodiazepine may be used in combination with carbamazepine, gabapentin, or valproic acid (in patients without liver disease or childbearing potential).8

Severe Symptoms

Patients with severe, but not complicated, withdrawal symptoms (eg, CIWA-Ar ≥20) should be treated with benzodiazepines or, as an alternative, phenobarbital (only use if the clinician is experienced with its use). Other options for patients with contraindications to benzodiazepine use include carbamazepine or gabapentin. Adjunctive agents may be used (eg, carbamazepine, gabapentin, and valproic acid).8

Risk for prolonged benzodiazepine use and misuse include memory impairment, psychomotor retardation, depression, and emotional anesthesia in addition to physiologic dependence.17 Because of the high addiction risk, alternative agents such as carbamazepine and gabapentin have less abuse potential, less toxicity, less sedation, and have demonstrated efficacy in the treatment of alcohol withdrawal syndrome.8

For ongoing management of AUD, the Department of Veterans Affairs and the Department of Defense recommends use of acamprosate, disulfiram, naltrexone (extended release), and/or topiramate (off-label) for the initial management of AUD.19 The American Psychiatric Association recommends first-line treatment of AUD with acamprosate and naltrexone, and use of disulfiram, gabapentin (off-label), and topiramate as second-line options.20

Gabapentin is beneficial for treating withdrawal symptoms in patients who will benefit from ongoing gabapentin use for treatment of AUD, according to the ASAM. Gabapentin (an analog of GABA) is not thought to modulate GABA receptors. Rather it is believed to enhance GABA activity or convert to GABA itself.21 Gabapentin is believed to normalize stress-induced GABA activation in the brain that is associated with alcohol dependence.22

Adjunctive therapies with supplemental thiamine, folate, and IV fluids are useful in correcting nutritional and electrolyte abnormalities associated with alcohol withdrawal syndrome symptoms. Folic acid 1 mg daily is recommended and thiamine 100 mg daily is shown to lower the risk of Wernicke encephalopathy.

Monitoring

The approach to monitoring during treatment should be individualized to each patient and influenced by symptom severity. Most patients are evaluated daily until symptoms begin to decrease and medication dose is reduced.11 The method or tool used to initially evaluate symptoms and their severity should be consistently used throughout follow-up.

Although each patient’s road to recovery is different, symptoms should begin to resolve within a week. Upon completion of treatment, a patient may need to be referred to a long-term outpatient facility, addiction specialist, or inpatient treatment facility for AUD.

Conclusion

The ASAM recommends use of pharmacologic agents for patients at risk of developing severe or complicated withdrawal symptoms as well as those with at least moderate alcohol withdrawal. Patient education on the benefits and risks of each therapy is essential to providing informed consent and shared decision-making.

Christian Lyle, PA-C, graduated from August University physician assistant program in 2020 and is working in gastroenterology in her hometown of Savannah, Georgia.

References

1. Excessive alcohol use. Centers for Disease Control and Prevention. Updated September 21, 2020. Accessed April 27, 2021. https://www.cdc.gov/chronicdisease/resources/publications/factsheets/alcohol.htm

2. Mason BJ, Quello S, Shadan F. Gabapentin for the treatment of alcohol use disorder. Expert Opin Investig Drugs. 2018;27(1):113-124. doi:10.1080/13543784.2018.1417383

3. SAMHSA, Center for Behavioral Health Statistics and Quality. 2019 National Survey on Drug Use and Health. Table 5.4B – alcohol use disorder in past year among persons aged 12 or older, by age group and demographic characteristics: percentages, 2018 and 2019. Accessed April 27, 2021. https://www.samhsa.gov/data/sites/default/files/reports/rpt29394/NSDUHDetailedTabs2019/NSDUHDetTabsSect5pe2019.htm#tab5-4b

4. U.S Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism. (2016). Alcohol Use Disorder: Comparison Between DSM-IV and DSM-5 (NIH Publication No. 13-7999). Retrieved from https://www.niaaa.nih.gov/sites/default/files/publications/DSMfact.pdf

5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.

6. Rahman A, Paul M. Delirium tremens (DT). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Updated November 18, 2018. Accessed April 29, 2021. https://www.ncbi.nlm.nih.gov/books/NBK482134/

7. Martin CS, Vergés A, Langenbucher JW, et al. Algorithm analysis of the DSM-5 alcohol withdrawal symptom. Alcohol Clin Exp Res. 2018;42(6):1073-1083. doi:10.1111/acer.13633

8. American Society of Addiction Medicine. Clinical practice guideline on alcohol withdrawal management. Updated January 23, 2020. Accessed April 29, 2021. https://www.asam.org/docs/default-source/quality-science/the_asam_clinical_practice_guideline_on_alcohol-1.pdf?sfvrsn=ba255c2_2

9. Zorumski CF, Isenberg KE. Insights into the structure and function of GABA-benzodiazepine receptors: ion channels and psychiatry. Am J Psychiatry. 1991;148(2):162-173.

10. Sigel E, Steinmann ME. Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012;287(48):40224-40231. doi:10.1074/jbc.R112.386664

11. DeSimone E, Tilleman J, Powell T. Treatment of alcohol withdrawal syndrome. US Pharm. 2014;39(11):38-41.

12. Mihic SJ, Ye Q, Wick MJ, et al. Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature. 1997;389(6649):385-389. doi:10.1038/38738.

13. Hoffman P, Grant K, Snell L, et al. NMDA receptors: role in ethanol withdrawal seizures. Ann N Y Acad Sci. 1992;654:52-60. doi:10.1111/j.1749-6632.1992.tb25955.x

14. Tsai G, Gastfriend DR, Coyle JT. The glutamatergic basis of human alcoholism. Am J Psychiatry. 1995;152(3):332-340. doi:10.1176/ajp.152.3.332

15. Feuerlein W, Ringer C, Küfner H, Antons K. Diagnosis of alcoholism: the Munich Alcoholism Test (MALT). Curr Alcohol. 1979;7:137-47. PMID: 552313.

16. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020.

17. Muncie HL Jr, Yasinian Y, Oge’ L. Outpatient management of alcohol withdrawal syndrome. Am Fam Physician. 2013;88(9):589-595.

18. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989;84(11):1353-7. doi:10.1111/j.1360-0443.1989.tb00737.x

19. Department of Veteran Affairs. Va/DoD Clinical Practice Guideline for the Management of Substance Use Disorders. Department of Veteran Affairs; December 2015. Accessed April 29, 2021. https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf

20. American Psychiatric Association. American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder. American Psychiatric Association; 2018. Accessed April 29, 2021. https://psychiatryonline.org/doi/book/10.1176/appi.books.9781615371969

21. Rey, JA. Anxiolytic and hypnotic drugs. In: Lippincotts illustrated reviews: Pharmacology, 6th ed. Wolters Kluwer; 2015:121-123.

22. Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174(1):70-77. doi:10.1001/jamainternmed.2013.11950

This article originally appeared on Clinical Advisor