Does Phenobarbital Really Help with Alcohol Withdrawal?
Individuals who develop alcohol use disorders (the clinical term used by the American Psychiatric Association that encompasses alcohol abuse and addiction to alcohol) require help to become abstinent from alcohol. Part of the diagnostic criteria for an alcohol use disorder is concerned with the development of physical dependence on alcohol (developing both tolerance and withdrawal to alcohol). Individuals with alcohol use disorders may have developed tolerance to alcohol, or they may have developed physical dependence on alcohol.
Withdrawal associated with alcohol can be quite severe, and in some cases, it can include a syndrome that is often referred to as DTs (delirium tremens).
DTs is a syndrome that consists of:
- Severe confusion and disorientation
- Psychosis (experiencing hallucinations and/or experiencing delusions
- Physical symptoms, such as fever, sweating, chills, etc.
- The potential to experience seizures
While there certainly is a relationship between the severity of an alcohol use disorder and the potential for a person to develop delirium tremens, it cannot be predicted who will develop delirium tremens with seizures and who will not, unless the person has displayed DTs in past attempts at recovery, in which case they are at a high risk to experience it again. Individuals who are diagnosed with moderate to severe alcohol use disorders according to the APA diagnostic criteria should be closely observed and monitored during the initial stages of recovery.
Most people who are undergoing withdrawal symptoms associated with the discontinuation of alcohol should be placed on a withdrawal management (medical detox) program to reduce the risk of relapse and to control any problems associated with symptoms that may occur. Seizures can produce significant brain damage and can even be fatal.
The medically assisted withdrawal management program that is most commonly used to assist with alcohol withdrawal is a tapering schedule of benzodiazepines (e.g., Librium [chlordiazepoxide], Valium [diazepam], Xanax [alprazolam], etc.).
However, in the past, barbiturates were typically used for many purposes that benzodiazepines are now used for, including to address symptoms of alcohol withdrawal. Phenobarbital is one drug that has been mentioned as a possible withdrawal management medication for alcohol use disorders.
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What Is Phenobarbital?
Phenobarbital is a barbiturate that is commonly used to control seizures, to treat anxiety in certain conditions, and as a muscle relaxant. Barbiturates like phenobarbital were potential medications that could be used to control the symptoms of withdrawal from alcohol before benzodiazepines were developed. Both benzodiazepines and barbiturates are central nervous system depressants and have similar mechanisms of actions. Barbiturates, like alcohol and benzodiazepines, also have a moderate to high potential for abuse and the development of physical dependence, and these drugs lost favor in the 1970s due to high rates of abuse.
Nonetheless, there is a significant body of research that investigates the utility of phenobarbital in the treatment of alcohol withdrawal. A study published in JAMA (Journal of the American Medical Association) in 2001 concluded that benzodiazepines should be the primary approach to the management of withdrawal in individuals with alcohol abuse. However, there is research that suggests that phenobarbital may be as effective as benzodiazepines in treating DTs that occurs as a result of alcohol withdrawal.
For instance, a randomized controlled trial published back in 1978 (one of the few such trials looking at the effectiveness of phenobarbital for alcohol withdrawal) compared Valium and phenobarbital in the treatment of delirium tremens related alcohol abuse in 91 patients. Phenobarbital was equivalent to Valium in individuals with mild to moderate symptoms associated with DTs and superior to Valium in the treatment of patients who were judged to have severe manifestations of alcohol withdrawal (DTs). However, the study has some severe methodological limitations.
A 2006 study in the Journal of Medical Toxicology reported that phenobarbital may be used in the place of benzodiazepines for the treatment of resistant alcohol withdrawal. A 2011 study reported in the Journal of Emergency Medicine compared phenobarbital and the benzodiazepine Ativan (lorazepam) in the treatment of alcohol withdrawal in the emergency department of several hospitals over a period of 48 hours. Phenobarbital was found to be equivalent to Ativan for the short-term treatment of alcohol withdrawal.
A 2015 study reported in the American Journal of Respiratory and Critical Care Medicine reported that phenobarbital treatment for DTs was equivalent to Librium when looking at variables associated with long-term recovery, such as relapse and other issues in critically ill patients. A study published in the journal Drug and Alcohol Dependence in 2016 found phenobarbital to be equivalent to the use of benzodiazepines in treating delirium tremors and seizures in individuals who were undergoing withdrawal from alcohol.
However, it should be noted that a study reported in the New England Journal of Medicine in 2003 reviewing recovery from alcohol and other drugs reported that even though phenobarbital had a low abuse potential and is used in substance use disorder treatment in about 10 percent of programs in the United States, it has little empirical evidence to support its use, and it has a poorer safety profile compared to benzodiazepines. This last statement is relevant. For instance, using phenobarbital in high doses or in individuals undergoing alcohol withdrawal can increase the risk of respiratory depression, which can lead to serious issues.
How Phenobarbital Might Be Used during Alcohol Withdrawal
One of the advantages to the use of phenobarbital is that it has a longer half-life than benzodiazepines, so it remains active in the system longer. Because the onset of seizures during withdrawal can be unpredictable, this may be advantageous. This means that the drug could be used less frequently than many benzodiazepines that are used to control withdrawal symptoms. Using a drug less frequently would also decrease the risk of an individual developing abuse issues with that drug. Phenobarbital may be also useful when combined with benzodiazepines because it can enhance their effects.
The actual administration of phenobarbital in the treatment of alcohol withdrawal depends on numerous factors, including the physician’s choice, the presentation of the individual in recovery, and other issues, such as co-occurring disorders, the philosophy of the treatment center, etc.
No medication is free of side effects, and phenobarbital use is associated with some side effects.
Side effects associated with phenobarbital include:
- Extreme sedation, lethargy, fatigue, or drowsiness
- Dizziness, headache, or confusion
- Respiratory suppression
- Nausea, vomiting, and/or stomach cramps
- Paradoxical effects, such as jitteriness, irritability, etc. (more likely to occur in children)
Phenobarbital does appear to have some usefulness in the treatment of DTs. A small percentage of treatment centers may actually use phenobarbital for this purpose, most likely in conjunction with benzodiazepines. The available research suggests that phenobarbital may be equivalent in its effectiveness to control seizures during withdrawal from alcohol, but there may also be some risks involved with its use.
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