Benzodiazepines constitute a large class of prescription drugs that are used medicinally for the treatment of anxiety, the control of seizures that can occur in disorders such as epilepsy, as muscle relaxants, for the treatment of withdrawal symptoms from alcohol and some other drugs, and several other uses. The drugs are classified as central nervous system depressants, meaning that they suppress or slow down the functioning of the actions in the brain and spinal cord. Their primary mechanism of action is to increase the efficiency of the neurotransmitter gamma aminobutyric acid (GABA), which is the most prominent inventory neurotransmitter in the central nervous system.
Benzodiazepines are classified as Schedule IV controlled substances by the United States Drug Enforcement Administration, indicating that while they do have significant medical uses, they are also drugs that have a moderate potential for abuse and for the development of physical and/or psychological dependence. These drugs can only be acquired legally with a prescription from a physician.
Because they have a varied number of medicinal uses, benzodiazepines are among the most prescribed drugs in the United States. In association with their medicinal effects, they also produce feelings of sedation, calmness, and even euphoria. As a result, they are also one of the most abused categories of drugs.
In terms of their abuse potential, a number of benzodiazepines are known to be significant drugs of abuse, such as Valium, Xanax, Ativan, and Klonopin. Most often, benzodiazepines are abused in conjunction with other drugs, such as alcohol, opiate drugs (e.g., morphine, heroin, Vicodin, OxyContin, etc.), cannabis, other benzodiazepines, and stimulant medications. When individuals abuse benzodiazepines in combination with other drugs, there are a number of potential dangers and complications that may occur.
Tolerance & Withdrawal
Physical Dependence on Benzodiazepines
Physical dependence on any substance consists of two related symptoms: tolerance and withdrawal. Tolerance to benzodiazepines develops rapidly in individuals who use them for more than just a few weeks. As individuals need more and more of the drug, the potential to develop withdrawal symptoms is also realized relatively rapidly. Tolerance refers to a physiological and emotional process where an individual no longer gets the same effect from a particular dose of a drug that they initially received when they began taking it. Individuals who develop tolerance need more of the drug to produce the same effects the drug once produced at lower doses.
A withdrawal syndrome or discontinuation syndrome is the second component of the development of physical dependence. This occurs when an individual’s system has adjusted itself to account for the presence of the drug in its tissues. When the levels of the drug in the system are depleted due to normal metabolic processes (detoxification), the individual system is thrown out of balance, and the person begins to experience a number of negative and unpleasant physical, psychological, and even cognitive symptoms.
The development of physical dependence on benzodiazepines depends on several factors:
The type of benzodiazepine the person regularly used (based on the half-life of the drug [see below] and the particular dose the person used regularly)
The frequency of use and the length of the period of time the person had been taking the drug
The manner in which the person took the drug on a regular basis (For example, physical dependence develops much more rapidly when individuals inject or snort these drugs. Taking a drug orally in pill form results in the development of physical dependence taking longer to occur.)
Abuse of multiple drugs (For example, physical dependence develops more quickly when multiple drugs are abused.)
Individual differences in metabolism
In addition, the withdrawal syndrome associated with any drug is also affected by how the person stops using the drug. Quitting the drug abruptly will result in a quicker appearance of withdrawal symptoms and more intense symptoms than slowly tapering the amount of the drug one takes.
Withdrawal from Benzodiazepines
The presentation of withdrawal symptoms as a result of discontinuing benzodiazepines is affected by the type of benzodiazepine a person uses. In general, benzodiazepines are divided into short-acting, intermediate-acting, and long-acting forms. Withdrawal symptoms may appear rather quickly after one has stopped using a short-acting benzodiazepine and may take longer to appear if an individual has stopped using a long-acting benzodiazepine. The duration of the withdrawal syndrome is often shorter for short-acting benzodiazepines than it is for long-acting benzodiazepines. This is because, in general, long-acting benzodiazepines remain in the system longer than short-acting benzodiazepines.
- Short-acting benzodiazepines have relatively short half-lives. They are eliminated from the body more quickly than other benzodiazepines; their half-lives are usually between one and six hours. The best-known short-acting benzodiazepine is Halcion (triazolam).
- Intermediate-acting benzodiazepines have longer half-lives than short-acting benzodiazepines, but not as long as most of the long-acting benzodiazepines. For most of intermediate-acting benzos, the half-life ranges from 6 to 20 hours. The most well-known intermediate-acting benzodiazepines are Xanax (alprazolam) and Ativan (lorazepam).
- Long-acting benzodiazepines have the longest half-lives, up to 50 hours. Valium (diazepam) and Librium (chlordiazepoxide) are in this category.
Thus, the development of withdrawal symptoms may vary depending on the particular benzodiazepine the individual took. According to the American Psychiatric Association, diagnostic criteria for withdrawal from anxiolytic drugs like benzodiazepines include two or more of these symptoms:
- Autonomic hyperactivity that can include symptoms like high blood pressure, increased or decreased body temperature, sweating, increased pulse rate of greater than 100 beats per minute, etc.
- Tremors in the hands
- Nausea and/or vomiting
- Hallucinations that are typically intermittent and can be visual, auditory, or even tactile
- Psychomotor agitation that manifests itself as a sort of restlessness or irritability (Individuals cannot seem to settle down.)
- The development of seizures
Research literature has described the withdrawal process from a number of different benzodiazepines. The withdrawal syndrome from benzodiazepines is similar to the withdrawal process that occurs in individuals with moderate to severe alcohol use disorders. Some of the effects of the withdrawal process will differ depending on the specific benzodiazepines; however, the overall process of withdrawal from benzodiazepines has been described as consisting of the following elements:
- Acute effects: The acute effects of withdrawal typically begin within the first 24-96 hours after the individual has stopped using the benzodiazepine. During this time, any of the symptoms listed by APA may occur. Additional symptoms, such as appetite loss, diarrhea, insomnia, fever, chills, confusion, depression, and cravings for the drug of choice, may also occur. The symptoms typically peak within a few days.
- Extended effects: An extended period of withdrawal following the peak of the acute symptoms also occurs. The extended period of withdrawal may last several weeks and will typically consist of symptoms that are less intense than those that occurred in the acute phase. Seizure potential still remains high during this period.
- Prolonged effects: Longer and more protracted periods of psychological and emotional issues are also reported. Often, sources report a protracted or post-acute withdrawal syndrome that occurs in many individuals who have discontinued benzodiazepines or other drugs. This syndrome is reported to last for months and even years in some, and it is primarily psychological in nature. Individuals experience periods of irritability, depression, mood swings, issues with motivation, and cravings for their drug of choice. This syndrome is reported to increase the risk for relapse in these individuals.Despite this syndrome being mentioned in a number of sources, it has never been accepted as a formal withdrawal syndrome by major medical associations in the United States, such as APA due to a lack of reliable and valid empirical research evidence to suggest that these issues represent a formal withdrawal process or withdrawal syndrome. Nonetheless, it is not uncommon for individuals in recovery to experience issues with mood swings, cravings, and motivation for quite some time after the physical withdrawal process has run its course. These symptoms most likely represent other issues associated with individuals who have developed substance use disorders as opposed to being a formal withdrawal syndrome.
Withdrawal Management for Benzodiazepine Abuse
It should be understood that major organizations such as the American Society of Addiction Medicine (the largest association of addiction medicine physicians in the United States) distinguish between detoxification (often abbreviated as detox) and withdrawal management. Detoxification represents a natural process that the body uses to rid itself of toxins and waste products. This process is accomplished primarily through the liver and occurs whether or not an individual is actively using drugs. Withdrawal management refers to a program designed to assist an individual in undergoing and tolerating the withdrawal process associated with drugs and/or alcohol. A physician-assisted withdrawal management program incorporates the use of addiction medicine physicians and medications to control and alleviate withdrawal symptoms. Even so, many withdrawal management programs are often referred to as “detox” programs.
The withdrawal syndrome associated with benzodiazepines can be potentially fatal due to the potential development of seizures.
Because of this complication, it is recommended that anyone who has abused or used benzodiazepines for more than a few weeks not attempt to discontinue them unless they are under the supervision of a physician. Physician-assisted detox for benzodiazepine most often consists of the physician prescribing the use of a long-term benzodiazepine to the individual and then slowly tapering down the dosage of that drug at specific intervals while the person’s system adjusts to decreasing amounts of the drug. This process results in a relatively safe, and symptom-free, detox process that may often cover a longer period of time than trying to withdraw from the drug without the tapering method.
Because of the potential dangers associated with detox from benzodiazepines, it is generally suggested that the withdrawal management program at least initially begin as an inpatient or residential program. Once the individual’s withdrawal process is under control, they may transition to an outpatient program or, depending on the situation, remain in an inpatient withdrawal management program until the process is completed. Other potential symptoms can be addressed by using specific medications, such as medications for nausea, headache, etc.
Several other medicines can also be used.
- Some antidepressants, particularly selective serotonin reuptake inhibitors, can be useful in addressing some withdrawal symptoms.
- In some cases, anticonvulsant medications may be useful.
- The muscle relaxant baclofen is often used to reduce cravings for drugs like benzodiazepines and alcohol.
- Melatonin can help to reduce anxiety, irritability, or insomnia associated with withdrawal process.
The implementation of a physician-assisted withdrawal management program also allows for the process to be personalized. Physicians are able to monitor the individual’s progress and adjust their treatment approach accordingly.
More treatment is needed following benzo detox. Simply completing a formal withdrawal program does not constitute engaging in a program of recovery from a substance use disorder. Instead, individuals must get involved in substance use disorder therapy, social support group participation, and other aspects of an organized substance use disorder treatment program in order for their recovery to be successful.