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Medication For Alcohol Use Disorder: Withdrawal Symptom Management and Maintenance

Alcohol Use Disorder (AUD) affects approximately 14.5 million people in the United States alone, making it a significant public health concern. According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), effective treatments, including medications, can greatly improve recovery outcomes. This article explores the medications used to manage AUD, focusing on those that alleviate withdrawal symptoms and those used for long-term maintenance. The World Development Report states that alcohol-related disorders affect 5-10% of the global population annually, contributing to 2% of the global burden of disease​​.

How Are Medication and Pharmacotherapy Used in The Treatment Of Alcohol Use Disorder?

Medication-assisted treatment (MAT) for Alcohol Use Disorder (AUD) involves using FDA-approved medications to manage withdrawal symptoms and support long-term recovery. In the short term, medications like benzodiazepines and anticonvulsants alleviate withdrawal symptoms such as anxiety, seizures, and agitation. For long-term maintenance, medications like naltrexone, acamprosate, and disulfiram help reduce cravings, stabilize brain chemistry, and deter relapse. Combining MAT with behavioral therapies, such as cognitive-behavioral therapy (CBT), enhances treatment effectiveness and supports sustained sobriety. This integrated approach improves overall recovery outcomes and quality of life for individuals with AUD​​.

The treatment of alcohol detoxification has significantly evolved from the traditional gradual weaning schedule of alcohol to the use of benzodiazepines and other modern drugs. Prompt pharmacological intervention is crucial in all cases of Alcohol Withdrawal Syndrome (AWS), as non-treatment or under-treatment can be fatal​​. Benzodiazepines are considered safe, effective, and the preferred treatment for AWS, with the best-studied options being diazepam, chlordiazepoxide, and lorazepam​​ according to Sachdeva A, Choudhary M, Chandra M. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond. J Clin Diagn Res. 2015.

What Medications Help With Alcohol Withdrawal?

Alcohol Withdrawal Syndrome (AWS) is a common condition in alcohol-dependent individuals who cease or significantly reduce their alcohol intake. Symptoms range from mild (e.g., tremors, irritability, anxiety) to severe (e.g., hallucinations, seizures, delirium tremens), occurring due to imbalances in neurotransmitter activity in the brain caused by the absence of alcohol according to Jaeger T, Lohr R, Pankratz VS. Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients. Mayo Clinic Procedure. 2001. Medications for alcohol withdrawal include benzodiazepines (diazepam, chlordiazepoxide, lorazepam) for anxiety, seizures, and agitation; anticonvulsants (carbamazepine, valproic acid) for seizure prevention; and adrenergic medications (clonidine, propranolol) for managing hypertension and tachycardia​​.

How Do Benzodiazepines like Diazepam, Chlordiazepoxide, and Lorazepam Help with Alcohol Withdrawal?

Benzodiazepines are a class of psychoactive drugs known for their sedative, hypnotic, anti-anxiety, anticonvulsant, and muscle relaxant properties. Diazepam (Valium), chlordiazepoxide (Librium), and lorazepam (Ativan) are commonly used benzodiazepines in the treatment of alcohol withdrawal syndrome (AWS).

Benzodiazepines work by enhancing the effect of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits activity in the brain. This increased GABAergic activity helps to calm the overexcited nervous system that results from alcohol withdrawal. They are effective in reducing symptoms such as anxiety, agitation, tremors, and preventing severe complications like seizures and delirium tremens (DTs).

Benzodiazepines are typically administered for short periods, usually lasting between 5 to 7 days, depending on the severity of the withdrawal symptoms. The dosing is often tailored to the patient’s needs and can be adjusted based on the clinical response. Long-acting benzodiazepines like diazepam and chlordiazepoxide are often preferred due to their prolonged effects, which help prevent rebound symptoms and maintain more consistent blood levels. Lorazepam, with its shorter half-life, is beneficial in patients with liver impairment as it is metabolized differently.

How Do Anticonvulsants like Carbamazepine and Valproic Acid Help with Alcohol Withdrawal?

Anticonvulsants are medications primarily used to treat epilepsy but are also effective in managing alcohol withdrawal symptoms. Carbamazepine (Tegretol) and valproic acid (Depakote) are two such anticonvulsants.

Anticonvulsants stabilize neural activity by reducing excessive electrical activity in the brain, which can be particularly beneficial in preventing seizures, a common and dangerous symptom of alcohol withdrawal. Carbamazepine works by blocking sodium channels, which helps to stabilize hyperexcited nerve membranes, while valproic acid increases GABA levels in the brain, enhancing inhibitory neurotransmission. These medications also help alleviate symptoms like agitation, anxiety, and mood disturbances.

Anticonvulsants are usually prescribed for a duration of 7 to 10 days during the acute phase of alcohol withdrawal. Their use is particularly indicated in patients who are at high risk of seizures or who have a history of withdrawal seizures. The dosage is carefully titrated to manage symptoms effectively while monitoring for potential side effects, such as dizziness or gastrointestinal disturbances.

How Do Adrenergic Medications like Clonidine and Propranolol Help with Alcohol Withdrawal?

Adrenergic medications affect the sympathetic nervous system, which controls the body’s ‘fight or flight’ response and are used to manage autonomic symptoms such as hypertension, tachycardia, and anxiety which occur during alcohol withdrawal. Clonidine is an alpha-2 adrenergic agonist, while propranolol is a non-selective beta-blocker.

Clonidine works by reducing the release of norepinephrine, which decreases sympathetic outflow and helps manage autonomic symptoms of withdrawal such as hypertension, tachycardia, sweating, and anxiety. Propranolol blocks beta-adrenergic receptors, which helps control elevated heart rate and blood pressure associated with alcohol withdrawal. These medications are particularly useful for managing the physical symptoms of autonomic hyperactivity without the sedative effects seen with other medications.

Adrenergic medications are typically used for a shorter period, often 3 to 5 days, during the acute withdrawal phase. They are administered as adjuncts to other medications like benzodiazepines, particularly when there is a need to control autonomic symptoms effectively. The dosage and duration depend on the severity of symptoms and the patient’s overall clinical condition.

What Medications Help With The Long-Term Maintenance Of Alcohol Use Disorder?

What Medications Help with the Long-Term Maintenance of Alcohol Use Disorder?

Alcohol Use Disorder (AUD) is a chronic condition characterized by an inability to control alcohol use despite adverse social, occupational, or health consequences. Long-term maintenance medications play a crucial role in reducing cravings, preventing relapse, and supporting sustained sobriety in individuals recovering from AUD. According to a comprehensive review from Crowley P. Long-term drug treatment of patients with alcohol dependence. Aust Prescr. 2015, these medications include naltrexone, acamprosate, disulfiram, baclofen, and topiramate​​.

How Does Naltrexone Help with Long-Term Maintenance of Alcohol Use Disorder?

Naltrexone is an opioid antagonist used in the long-term maintenance of AUD. It is available in oral form (ReVia) and as an extended-release injectable (Vivitrol).

Naltrexone works by blocking opioid receptors in the brain, which reduces the pleasurable effects of alcohol and diminishes cravings. This mechanism helps individuals reduce their alcohol consumption and supports sustained abstinence.

Naltrexone can be used long-term, with the oral form taken daily and the injectable form administered monthly. The duration of treatment depends on individual needs and response, with many patients benefiting from extended use to maintain sobriety. Continuous use under medical supervision ensures its effectiveness and minimizes the risk of relapse​​.

How Does Acamprosate Help with Long-Term Maintenance of Alcohol Use Disorder?

Acamprosate (brand name Campral) is a medication used to support abstinence in individuals with AUD. It is taken orally in the form of tablets.

Acamprosate works by stabilizing the chemical balance in the brain that is disrupted by chronic alcohol use. It enhances the inhibitory neurotransmission of GABA and modulates the excitatory neurotransmission of glutamate. This stabilization helps reduce symptoms of post-acute withdrawal, such as anxiety, insomnia, and mood disturbances, thereby supporting long-term abstinence.

Acamprosate is typically prescribed for long-term use, with the standard regimen being three times daily. The duration of treatment can extend for a year or more, depending on the patient’s progress and response to therapy. Its use is most effective when combined with psychosocial support and counseling​​.

How Does Disulfiram Help with Long-Term Maintenance of Alcohol Use Disorder?

Disulfiram (brand name Antabuse) is an alcohol deterrent medication used in the long-term maintenance of AUD. It is taken orally in tablet form.

Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, which results in the accumulation of acetaldehyde when alcohol is consumed. This accumulation causes unpleasant reactions, including nausea, vomiting, headache, and flushing. The aversive effects discourage individuals from consuming alcohol, thereby aiding in the maintenance of abstinence.

Disulfiram is intended for long-term use, typically prescribed to be taken once daily. The duration of treatment varies based on individual needs and commitment to sobriety. Regular monitoring and adherence to the medication are crucial to ensure its effectiveness and safety​​.

How Does Baclofen Help with Long-Term Maintenance of Alcohol Use Disorder?

Baclofen is a GABA receptor agonist used off-label for the maintenance of AUD, particularly in patients with chronic and severe disease.

Baclofen reduces alcohol’s reinforcing, rewarding, and motivational properties by stimulating GABA receptors, which are neuroinhibitory. This helps in reducing cravings and maintaining abstinence​​.

Baclofen is typically started at a low dose, such as 5 mg three times a day, and titrated up to an optimum dose ranging between 30 mg and 75 mg. Treatment duration depends on patient response and clinical condition. Baclofen should be used with caution due to its toxicity in overdose​​.

How Does Topiramate Help with Long-Term Maintenance of Alcohol Use Disorder?

Topiramate is an antiepileptic medication used off-label for the maintenance of AUD. It has neuroprotective and mood-stabilizing properties.

Topiramate reduces the rewarding effects of alcohol by suppressing dopamine release and normalizing dopamine activity. This helps in reducing cravings and managing withdrawal symptoms. It is particularly beneficial for patients with comorbid psychiatric disorders​​.

Topiramate is started at a low dose of 25 mg daily, with a slow titration up to a maximum of 150 mg twice daily. The duration of treatment is tailored to individual needs and response​​.

How Long Does Alcohol Withdrawal Last?

The duration of alcohol withdrawal can vary significantly depending on the individual and the severity of their alcohol dependence. Generally, alcohol withdrawal follows a timeline that can be divided into three phases:

  1. Early Withdrawal Symptoms (6-12 Hours):
    • Symptoms begin as early as 6 hours after the last drink.
    • Common early symptoms include anxiety, insomnia, nausea, loss of appetite, sweating, tremors, and mild headache.
  2. Peak Withdrawal Symptoms (24-48 Hours):
    • Symptoms usually peak within 24 to 48 hours.
    • During this period, individuals may experience increased anxiety, confusion, irritability, rapid heart rate, and elevated blood pressure.
    • Some individuals may develop more severe symptoms such as hallucinations and seizures.
  3. Late Withdrawal Symptoms (48-72 Hours and Beyond):
    • Severe withdrawal symptoms, including delirium tremens (DTs), can begin 48 to 72 hours after the last drink.
    • Symptoms of DTs include severe agitation, fever, hallucinations, high blood pressure, and confusion.
    • The risk of DTs can persist for up to a week or longer in severe cases.

Duration of Withdrawal:

  • Mild to Moderate Withdrawal: Symptoms generally start to subside within 4 to 5 days.
  • Severe Withdrawal: Symptoms can last for a week or more, with some lingering effects like anxiety, insomnia, and mood disturbances potentially lasting for several weeks.

The exact duration and severity of alcohol withdrawal depend on factors such as the individual’s history of alcohol use, the amount of alcohol consumed, the duration of heavy drinking, and overall health. Medical supervision during alcohol withdrawal is crucial to manage symptoms effectively and reduce the risk of complications.

What other drugs that help with alcohol use disorder?

However, a recent study conducted at Yale University reveals that a medication in use around since the mid-70s – a high-blood pressure drug called prazosin hydrochloride, commercial name Prazosin – is effective in reducing relapse rates for people diagnosed with AUD who experience severe alcohol withdrawal symptoms. By week 12, participants with high alcohol withdrawal symptoms on prazosin reported significantly fewer heavy drinking days (7.07%) and overall drinking days (27.46%) compared to those on placebo, who had 35.58% heavy drinking days and 58.47% drinking days. Prazosin also significantly improved anxiety, depression, and alcohol craving in these participants​​ according to Rajita Sinha et al’s 2020 study on moderation of Prazosin’s Efficacy by Alcohol Withdrawal Symptoms.

Researchers recruited 100 people diagnosed with alcohol use disorder (AUD) who reported varying degrees of alcohol withdrawal symptoms, from mild to severe. Participants were divided into two groups. One received a placebo (a pill with no therapeutic effect) and the other received the blood pressure medication Prazosin.

Over a 12-week period, researchers measured the following outcomes:

  • Self-reported drinking days
  • Self-reported heavy drinking days
  • Average drinks per day
  • Average daily mood (depressive state)
  • Presence/absence of anxiety
  • Presence/absence of cravings
  • Sleep quality

After collecting and analyzing the data, the research team published their results in The American Journal of Psychiatry. Here’s what they found.

  • Over the 12-week period, participants with severe withdrawal symptoms reported:
    • 7 heavy drinking days
    • 27 drinking days
    • Reduced depression
    • Reduced anxiety
    • Fewer cravings
  • Over the 12-week period, participants with no withdrawal symptoms or mild withdrawal symptoms reported:
    • 58 drinking days
    • 25 heavy drinking days
    • No improvements in depression or anxiety
    • No reduction in cravings

Those results beg the following question. Why does the medication reduce heavy drinking days, drinking days, depression, anxiety, and cravings for people who experience severe symptoms, but not for people whose symptoms are mild?

Recovery from Alcohol Use Disorder

Whenever we talk about medication that helps recovery and treatment for alcohol use disorder, we need to remember – and remind our readers – that an overwhelming amount of data indicates that treatment for alcohol use disorder (AUD) should be integrated, patient-specific, and involve individual therapy, group therapy, community support, and lifestyle/behavioral change.

In other words, addiction professionals caution against hoping for a magic pill of some kind that will cure alcoholism and depression, and other symptoms.

This medication offers hope because it has the potential to help people in treatment make it through the first few days of abstinence, when cravings are the most intense and the risk of relapse is highest. When they make it past this challenging period and their brains and bodies begin to re-establish homeostasis (balance) in the absence of alcohol, they can begin to fully participate in the type of treatment activities that lead to sustainable sobriety and lifelong recovery.

Sources

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  3. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Diagnosis and management of acute alcohol withdrawal. CMAJ. 1999;160(5):675-80.
  4. Rosenbloom A. Emerging treatment options in the alcohol withdrawal syndrome. J Clin Psychiatry. 1988;49:28-32.
  5. Srisurapanont M, Jarusuraisin N. Naltrexone for the treatment of alcoholism: a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2005;8:267-80.
  6. Pettinati HM, O’Brien CP, Rabinowitz AR, Wortman SP, Oslin DW, Kampman KM, et al. The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. J Clin Psychopharmacol. 2006;26:610-25.
  7. Mason BJ, Heyser CJ. The neurobiology, clinical efficacy and safety of acamprosate in the treatment of alcohol dependence. Expert Opin Drug Saf. 2010;9:177-88.
  8. Mann K, Kiefer F, Spanagel R, Littleton J. Acamprosate: recent findings and future research directions. Alcohol Clin Exp Res. 2008;32:1105-10.
  9. VA/DoD Clinical practice guideline for management of substance use disorders (SUD). Department of Veterans Affairs, Department of Defense. Version 2. Washington, DC: Department of Veterans Affairs; 2009. p. 67.
  10. Addolorato G, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G. Ability of baclofen in reducing alcohol craving and intake: II–Preliminary clinical evidence. Alcohol Clin Exp Res. 2000;24:67-71.
  11. Leggio L, Ferrulli A, Zambon A, Caputo F, Kenna GA, Swift RM, et al. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection. Addict Behav. 2012;37:561-4.
  12. Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007;370:1915-22.

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