The previous front line treatment for alcohol 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.
Benzos, along with certain other medication classes, are cross tolerant to alcohol. In the case of alcohol and benzos the mechanisms of action are very similar, and in practice means that taking a benzo will reduce symptoms of alcohol withdrawal and vice versa. Both alcohol and benzos work by interacting with the GABA system of the brain. GABA is a critical neurotransmitter in brain function which acts to depress, moderate, and decrease excitability in a wide array of neurological processes.
Benzos act by stimulating GABA receptors and increasing function at receptor sites, particularly at the GABA-α receptor site. This is similar to alcohol which increases global GABA activity in the brain, leading in part to the total depressant effect which is produced through alcohol use. When someone is experiencing withdrawal, their brain’s sensitivity to GABA is greatly lowered. This leads to neurological hyperactivity with no available way to slow down. This results in increased anxiety, vital function hyperactivity, and a greatly increased possibility to suffer seizures.
Alcohol withdrawal is caused primarily by imbalances in levels of the neurotransmitters GABA and glutamate. The brain is able to correct this imbalance, but it requires time. In severe alcohol addiction, this imbalance can be so severe as to be potentially fatal. Since benzos work directly on the GABA system they can greatly reduce the risk of death and also reduce the level of discomfort while the brain’s healing process begins.
Benzodiazepines are typically used heavily very early on in treatment with the purpose of stabilizing someone’s vital signs, reducing withdrawal symptoms, and hopefully preventing seizures. Since they are cross tolerant to alcohol, they are extremely effective at managing the dangerous symptoms produced during alcohol withdrawal. They may be used for short periods of several weeks, but because of their addictive potential, benzos are not commonly used for long periods in the treatment of alcohol withdrawal symptoms.
The most common detox treatment regime for alcohol withdrawal is for someone to be administered intravenous short-acting but potent benzos, such as lorazepam while changing to longer-acting but subtler benzos as days pass. The first few hours typically require large doses of IV benzos to reduce the risk of seizure or dangerous cardiovascular complications. They are typically administered on an as-needed basis until the medical team can get a good idea of the overall severity of symptoms. Once the worst of the danger is past this may be switched to oral doses of intermediate to long-acting benzos, typically after 3-4 days.
Finally, after the worst danger has passed, usually after 4-7 days, someone may be discharged and prescribed a “taper” prescription to take over the next week or two. A taper prescription is when someone will, for example, start out taking 4 pills a day for several days and slowly decrease the amount taken over a week or two until they are out of medication. This is most commonly chlordiazepoxide, but other benzos may be used as the situation requires. Anxiety is extremely common during alcohol withdrawal and since benzodiazepines are primarily used as anti-anxiety medications they provide relief for this psychological symptom as well.
While there are well over a dozen benzodiazepines used to treat a variety of conditions, there are only a handful of frequently used benzodiazepines for alcohol withdrawal. The choice of which benzo to use for withdrawal typically has to do with the strength of the benzo compared to its half-life. A medication’s half-life is a measure of the body’s ability to eliminate half of the maximum levels of medication from the blood.
There are also health factors that play a role in a doctor’s choice of benzo in a particular patient. While benzos are fairly safe, certain health conditions may produce dangerous complications when a specific benzo is used. Due to this, there are certain benzos that are contra-indicated in special circumstances. Let’s look at the individual strengths and weaknesses of the most commonly used benzos.
Some of the benzos most frequently used benzodiazepine for alcohol withdrawal and their preferred treatment methods include:
Approved by the FDA in 1961, chlordiazepoxide is the first benzo to be used to treat alcohol withdrawal symptoms. It reaches the strongest effect within 2-4 hours of delivery. It is also quite long-acting as the half-life is between 24-48 hours, but active metabolites may persist in the body for dozens of hours longer than this. It is not particularly potent compared to many other benzos, typically requiring initial doses of around 50-100mg, but not to exceed 300mg daily. Chlordiazepoxide is the most commonly used benzo for alcohol withdrawal, but due to its relative weakness, it is only used in mild cases.
Diazepam was initially approved by the FDA in 1963. Diazepam is often the first choice for treating moderate to severe alcohol withdrawal symptoms. It reaches peak strength quite quickly, within 1 hour of delivery. This is a long-acting benzo with a half-life elimination of roughly 48 hours but this varies depending on several factors. Elimination half-life is significantly longer in patients with liver disease or elderly patients, therefore the use of diazepam is avoided in patients fitting either of these criteria. Standard doses for alcohol withdrawal entail an initial 5-10mg intravenous dose followed by 5-20mg doses as needed to reduce withdrawal symptoms. Doses of diazepam should not exceed 250mg in any 8 hour period.
Approved by the FDA in 1977 for the oral medication and in 1980 for intravenous use, this medication is currently among the first line of treatment for alcohol withdrawal symptoms. It is fairly potent and short-acting, reaching peak strength within 1-1½ hour(s) after delivery and is metabolized easily, leading to lower toxicities. Because of its short half-life of 12 hours, lorazepam is often used as needed to reduce symptoms, typically delivered in 1-4mg intravenous injections in 15-minute intervals. This method may be used to initially gain control of symptoms, but the amount delivered should not exceed 50mg in any 8 hour period. Lorazepam is well tolerated in elderly patients or patients with liver disease and is the first choice for patients that fit these criteria.
Approved by the FDA in 1965, the medication oxazepam is actually a synthetic version of a natural metabolite produced by the body when taking diazepam. Oxazepam is similar to chlordiazepoxide in strength being fairly weak with a slow onset, reaching peak strength around 2-3 hours after delivery. It is an intermediate-acting benzo with a half-life of around 8 hours. This half-life is slightly increased with advanced age (80+ years). Oxazepam is commonly used in an initial dose of between 15-30mg followed by a similar dose every 6-8 hours, but not to exceed 150mgs in any 24 hour period.
While benzos are extremely effective at treating alcohol withdrawal, they do come with their own set of unique risks. Being cross tolerant to alcohol, they are also capable of producing tolerance which means over time it will take more medication to produce the same effect. There are also issues with benzo toxicity in patients with reduced liver function due to illness or advanced age. While being very effective in the application for alcohol withdrawal, they must be used judiciously and carefully so as to minimize the possibility of dangerous complications.
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.
Benzo addiction is a very real problem and produces symptoms almost identical to alcohol withdrawal, except there is no treatment medication for benzo withdrawal which is not itself a benzo. Using benzos for prolonged periods will produce tolerance, requiring even more benzos to achieve the same level of sedation. Once this point has been reached, withdrawal will occur unless someone continues to take them.
Benzo withdrawal is extremely dangerous as it comes with a similar risk of seizure, brain damage, and death as does alcohol withdrawal. Furthermore, benzo withdrawal can leave lingering psychological symptoms such as insomnia, depression, or panic attacks for many months or and in some cases years after they have been discontinued. The only currently effective treatment for benzo addiction and withdrawal is diazepam stabilization and tapering. Itself a benzo, diazepam can be used to manage the dangers but the process of benzo withdrawal will be extremely unpleasant in the best of cases.
While benzodiazepines are extremely effective, they are not the only alcohol withdrawal medication available. There are a variety of others, along with therapeutic techniques and support services which are commonly used in treating withdrawal. Entering an alcohol detox center will provide someone with access and consultation on which medications and therapies may be right for them, as well as any unique risks these medications may pose. Alcohol withdrawal is painful, but with the willingness to ask and receive help, there is life afterward.
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