Alcohol Withdrawal Medications

The Vital Importance of Medications

The major issues related to alcohol withdrawal, both acute and post-acute, involve the neurotransmitters GABA, glutamate, norepinephrine, and to a lesser degree dopamine and serotonin. Most alcohol withdrawal medications work either directly or indirectly on these neurotransmitter pathways, some more selectively than others.

The issues that arise in acute and post-acute alcohol withdrawal are discrete problems that require specific medications to treat each set of symptoms in turn. Additionally, there are quite a few alcohol detox medications that are used in special circumstances, such as refractory withdrawal and refractory delirium tremens. Refractory simply means that it is not responding to normal treatment methods. These medications are not used regularly, as refractory issues are by definition uncommon, but are considered first-line treatment for refractory complications.

Without withdrawal medications, the risk of serious health complications during detox increases substantially.

Medications Used During Alcohol Detox

The acute phase of withdrawal is extremely dangerous because of the risk of seizure, heart problems, delirium, and death. Thankfully, there are a number of detox medications that effectively treat these issues, and provide a safe withdrawal experience when coupled with appropriate medical oversight.

Benzos as a First Line Treatment

The use of benzodiazepines for alcohol withdrawal is one of the most effective treatments to minimize the risks and discomfort. Since they work in a similar way to alcohol, these medications can make someone much more comfortable, while still allowing withdrawal to complete. That being said, using them still comes with a certain degree of risk. Some of the benzos most commonly used to treat alcohol withdrawal include:

• Chlordiazepoxide (Librium): Chlordiazepoxide is the most commonly used benzo for alcohol withdrawal, but due to its relative weakness, it is only used in mild cases.
• Lorazepam (Ativan): Ativan is currently among the first line of treatment for moderate to severe alcohol withdrawal symptoms.
• Oxazepam (Serax): Oxazepam is similar to chlordiazepoxide in strength, as it is fairly weak with a slow onset, reaching peak strength around 2-3 hours after delivery.
• Diazepam (Valium): Diazepam is often the first choice for treating moderate to severe alcohol withdrawal symptoms.

The previous front-line treatment for withdrawal was the barbiturate class of medication. While these medications were effective, they posed very serious risks as well. They operate in a similar way to benzos but lead to greater central nervous system depression such as lowered breathing and heart rate. Additionally, barbiturate toxicity is extremely dangerous and there is currently no antidote for a barbiturate overdose.

While barbiturates are like blunt instruments that operate in a crude manner, using benzodiazepines for alcohol withdrawal has been proven to be much more precise and targeted. Since they work more subtly, there is much less unintentional CNS depression produced by benzos and there is more variety in strength and duration. Depending on the exact benzo used, the elimination rate can be between 2-100+ hours, leading to greater treatment customization. Finally, in the event of a benzo overdose, there are antidotes available to reverse the effects such as flumazenil. That being said, it is very dangerous to use a benzo antagonist during alcohol withdrawal, as it greatly increases the likelihood of a seizure occurring.

Patients With Reduced Liver Function

Benzodiazepine metabolism occurs primarily in the liver. While benzos themselves are unlikely to cause liver injury, their metabolism may be altered or slowed in patients with reduced liver function, leading to slower clearance and elimination. This has the result of producing stronger sedation at lower doses since the medications stay in the body longer. Using long-acting benzos can lead to unintentional overdose or dangerous levels of sedation. In patients with reduced liver function, such as cirrhosis or elderly patients, shorter-acting benzos such as lorazepam are preferred since they have a much lower risk of dangerous side effects.

Secondary Withdrawal Medications

While benzodiazepines are the first choice, there is a variety of other medications that may also be effective. Some of the other most commonly used alcohol withdrawal medications include:

• Blood Pressure Medications: Either beta-blockers or the alpha-2 agonist clonidine (Catapres), these medications can lower blood pressure and sometimes reduce anxiety or pain. Some commonly used beta-blockers include metoprolol (Lopressor), propranolol (Inderal), and atenolol (Tenormin).
• GABA Agents: These may be used off-label for withdrawal, but have shown great promise. Gabapentin (Neurontin), while not technically a GABA agonist, is an anticonvulsant and is also used to treat certain kinds of pain, while baclofen (Gablofen) is used to treat muscle spasms. These can help reduce the GABA imbalances during withdrawal.
• Barbiturates: In the absence of available benzodiazepines, or if a patient is not responding to them, older barbiturates such as phenobarbital (Luminal) may be used as an adjunct withdrawal medication.
• Anticonvulsants: Certain drugs of this class, such as carbamazepine (Tegretol) and valproic acid (Depakote), have been found useful in reducing the subjective symptoms of acute alcohol withdrawal. They may also prevent status epilepticus seizures during delirium tremens. Additionally, newer medications in this class such as zonisamide (Zonegran) and topiramate (Topamax) may more effectively reduce the subjective experience of acute withdrawal symptoms.
• Anesthetics: Typically used as a last resort in refractory alcohol withdrawal and refractory DT cases, these medications are used to lower the hyperactive vital signs to safer levels. The most commonly used medication of this type is propofol (Diprivan), although the use of this medication is reserved as it comes with its own set of risks.

Medications for Post-Acute Alcohol Withdrawal

The post-acute phase of alcohol withdrawal presents its own challenges, mainly in the realm of mental symptoms such as depression, cravings, and anxiety. Luckily, there are a variety of medications that are commonly used to treat these symptoms as well. The most widely used include:

• Naltrexone (Vivitrol): Originally used to treat heroin addiction, this medication has also proved very effective at treating alcohol use disorders. It is now standard practice to use this medication during and after detox. It is an opioid antagonist, which acts on the natural opioid system of the brain and can reduce cravings for alcohol or other drugs.
• Acamprosate (Campral): The exact way this medication works is not well understood, however, it does appear to lower glutamate levels as well as raise GABA levels in the brain. This may help to reduce the negative symptoms of post-acute alcohol withdrawal. Used as part of post-detox treatment, when this medication is used in conjunction with support groups and therapy, it has been shown to improve adherence to treatment plans and may reduce cravings.
• Antidepressants: This is a large and general classification of medications which includes SSRI and tricyclic antidepressants. These are used to treat depression and some may also help with anxiety and insomnia. Some of the more common SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and escitalopram (Lexapro). The commonly used tricyclic antidepressants include amitriptyline (Elavil), desipramine (Norpramin), and imipramine (Tofranil). It is not uncommon for these symptoms to persist for many months after detox, so antidepressants are one of the most frequently prescribed medications during post-acute withdrawal.
• Disulfiram (Antabuse): This is a unique medication whose only use is in the treatment of alcohol use disorder. This medication changes the way alcohol is metabolized and produces very strong negative consequences if alcohol is consumed while taking this medication. The symptoms of drinking while on disulfiram include chest pain, nausea, dizziness, intense thirst, and elevated heart rate.
• Propranolol (Inderal): Aside from the originally intended use as a medication to manage blood pressure, it also helps reduce anxiety in a non-mind-altering manner.

Investigational Alcohol Withdrawal Medications

Due to the large numbers of people seeking treatment for alcohol use disorder, there are several promising alcohol withdrawal medications that are currently being investigated for use in the United States and Europe. Since these medications are under development, these results are inconclusive at the present, and any attempt to try these treatments should be done only under the supervision of a doctor.

• Memantine (Axura): This is a fairly new medication intended to treat the dementia-like symptoms of Alzheimer’s disease. It works by blocking glutamate receptors which lead to the neural hyperactive symptoms experienced during acute alcohol withdrawal. In some studies, it has been shown to be as effective as diazepam in reducing the subjective discomfort felt, and even more effective than diazepam at reducing tremors. It has been recommended as an adjunct treatment medication.
• Clomethiazole (Heminevrin): Commonly used in Europe as an acute stage alcohol withdrawal medication this drug is a GABA agonist which acts as both a sedative and an anticonvulsant. Compared to diazepam, it produces a shorter withdrawal period although the subjective experience of acute withdrawal was similar between the two.
• Tiapride (Tiapridal): A highly selective dopamine agent, this drug is commonly used as an antipsychotic and tremor reducer. It has been studied for use in treating acute alcohol withdrawal and specifically when combined with carbamazepine it has shown promise as an adjunct medication.
• Pregabalin (Lyrica): A GABA agonist similar to gabapentin, this medication is commonly used to treat chronic nerve pain. The mechanism of action is not fully understood, but it may help reduce anxiety and cravings during post-acute withdrawal.
• Lamotrigine (Lamictal): An anticonvulsant as well as a bipolar treatment medication, it has promise as a treatment for co-occurring mental health issues and alcohol use disorder. When combined with clozapine, it has shown to reduce relapse and cravings in patients with co-occurring refractory schizophrenia and alcohol use disorder. Likewise, it has shown great promise in treating co-occurring bipolar disorders with alcohol use disorder, both reducing cravings and improving mood in general.
• Tiagabine (Gabitril): A GABA agent used as an anticonvulsant as well as a treatment for panic disorders, the exact way this potential alcohol withdrawal medication works is not fully understood. It has been shown to reduce relapse rates in double-blind studies and is being investigated further for use during post-acute withdrawal.

Detox is Vital

These medications are some of the most well-known, but there are many other options available. In addition to medications, therapeutic techniques and dietary supplements have been found helpful and effective for the treatment of alcohol withdrawal. Finding a professional alcohol detox center will give someone access to trained medical professionals who can help them discover the available medications and treatments which will be the most effective and applicable to them.