Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN
Written By: Phillippe Greenough
Article Updated: 11/22/2021
Number of References: 14 Sources
Benzodiazepine withdrawal is one of the most dangerous withdrawal syndromes of any drug. Not only can it be fatal, but unmonitored withdrawal from benzodiazepines can cause seizures, brain damage, and a variety of negative complications. Aside from the direct risks, the symptoms themselves are extremely unpleasant, manifesting both physically and psychologically. Additionally, the long term symptoms may last for many months or even years. There are many treatment options available for benzo withdrawal which may minimize the risks as well as the discomfort.
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There are many different types of benzodiazepines (benzos) used in medicine today, but only a handful are commonly abused. Due to the particulars of their metabolism, the time to onset, and duration of action, these particular benzos see widespread abuse and addiction. While they all work in very similar ways, they each have distinct characteristics that give them some unique characteristics.
Benzos can be divided into 3 general categories, which are fairly self-explanatory:
All benzos work primarily on the GABA system in the brain. This is a neurotransmitter which is a major inhibitor and signal reducer in the brain which works to slow and calm brain signaling down. This produces less anxiety and excitability in therapeutic doses and can prevent seizures, but when abused in supratherapeutic doses these drugs can produce euphoria, impaired memory, and a loss of inhibitions. The way these different benzos interact with the GABA system can vary slightly which leads to minor differences in effect between them.
Some of the most commonly abused benzodiazepines include:
There is some variability in the withdrawal timeline both between individuals between different benzo drugs. Some of the longer-acting benzos will have less intense symptoms but last longer, while the short-acting benzos have more intense acute withdrawal symptoms which resolve more quickly. The acute phase of withdrawal may begin within hours to days of the last time benzos were used. This variability depends on the specific benzo someone was using. Once acute withdrawal has begun, the symptoms will escalate quickly over the course of a day or two and may persist for around 2 weeks.
That being said, we can illustrate a rough timeline for withdrawal from short-acting benzos such as alprazolam below:
Within 2 to 4 days of last benzo use, withdrawal symptoms will begin to appear. The first symptoms to appear are commonly an increase in nervousness and anxiety along with heavy, constant sweating. Stress-induced stomach issues are also very common during the first week. This is commonly in the form of diarrhea but rarely can manifest as constipation as well. Several days after withdrawal has begun, the risk of seizure will begin to rise and typically peaks between 5 to 7 days into withdrawal. Seizure risk can still be very high during the second week, and all of the prior symptoms will still be present and are often near their peak intensity. The risk of psychosis or delirium may be at its peak as well since the prior week has only deteriorated someone’s mental state. Towards the end of the second week, the acute symptoms will likely begin to resolve.
Some of the symptoms that may be experienced during the first 2 weeks of benzo withdrawal can include:
The beginning of the third week will often be marked by the relief of some of the worst symptoms. The acute phase of withdrawal typically concludes near the end of the second or the beginning of the third week. Seizure risk is greatly reduced by now and hallucinations and tremors should completely resolve within the first few days of week three. By the beginning of week four, the majority of the acute withdrawal symptoms will commonly be resolved. The post-acute phase will begin around this time, but these symptoms are much less intense and will continue to decrease in intensity over the following weeks or months. Anxiety and depression will reduce consistently and cognitive issues may improve more slowly. There can be significant variability in the post-acute withdrawal timeline due to a wide variety of factors.
Some of the symptoms that may be expected during the third and fourth week of benzo withdrawal may include:
While the acute phase of benzo withdrawal may only last around 2 weeks, the post-acute phase may persist for several months. The symptoms will be much less intense, but the extended duration of this phase can make it a mentally exhausting experience. While the physical dangers may have passed, this phase is characterized by lingering psychological symptoms which in rare cases have lasted for years.
Some of the symptoms most common during post-acute benzo withdrawal include:
These symptoms may still be uncomfortable or disruptive to someone’s life, but they will continue to improve so long as someone stays away from using benzos. Additional care in the form of psychiatric care or clinical therapy can help support and accelerate the recovery process. Depression and anxiety will typically resolve in time, but there have been instances of certain cognitive deficits such as memory problems lasting for many years, or even indefinitely.
There is a wide range of factors that can contribute to the intensity of benzo withdrawal. Some of these are under the control of a person addicted to benzos such as environmental and behavioral factors, while others are not. That being said, there is still quite a bit of variability between people regarding withdrawal severity. Some individuals will make a complete recovery in a handful of months or even weeks, while others may have lingering symptoms that persist for many years. There are also those who never fully recover, and suffer from cognitive and emotional problems for the rest of their lives. There are a few specific factors that can contribute to both the intensity and duration of benzo withdrawal symptoms.
Some of the largest factors which contribute to benzodiazepine withdrawal include:
These first three factors are distinct, yet intimately related. Genetics plays a role in regards to someone’s likelihood to engage in addictive behavior as well as co-occurring mental health issues. If someone had relatives who were addicted to substances of any kind, then they have a greater chance of exhibiting addictive behavior themselves. This can not only increase the risk of developing an addiction but also speed up the process of addiction, with people prone to addictive behavior becoming physically dependent much more quickly than those who have no family history of addiction.
Co-occurring mental health issues also play a large role in that people suffering from anxiety and depression have a much higher rate of drug abuse than those who do not suffer from mental health issues. While not a direct cause, these mental health issues may encourage or accelerate someone’s benzo use, leading to a shorter time to dependence as well as using larger amounts.
Someone’s age at the time of benzodiazepine use and addiction has a very large impact on the severity of their withdrawal symptoms as well as the duration and possibility of a full recovery. It has been documented that elderly people suffer much greater cognitive deficits during and after benzo withdrawal. In addition, they typically recover more slowly, and the degree to which they recover is often not as complete as it is in younger benzo addicts. That being said, someone who becomes addicted to benzos at a younger age will frequently have poorer outcomes with regard to treatment and relapse into chronic benzo use.
The particular benzo someone uses, as well as the amounts and duration of use probably play the largest direct role in the intensity and duration of withdrawal symptoms. Short-acting benzos such as alprazolam will produce more intense withdrawal symptoms than a longer-acting one such as diazepam. That being said, short-acting benzos will typically have a shorter withdrawal period than longer-acting ones. Additionally, the amounts someone uses also affect the intensity and duration. The more benzos someone does, the more the brain has to alter GABA function to maintain balance. The larger the degree of downregulation, the more uncomfortable someone will be during withdrawal. Finally, the length of time someone uses benzos also affects the degree of downregulation. The longer benzos are used, the more complete this downregulation process becomes, and subsequently the longer it takes to reverse.
To get a more comprehensive picture of benzo withdrawal, it will be helpful to know more about how benzodiazepines work. This class of medication is known as an anxiolytic, or anti-anxiety medication. Benzos are some of the most commonly prescribed medications in the world, as they are very effective for the treatment of anxiety disorders, seizure disorders, alcohol withdrawal, and insomnia. These medications work primarily on the neurotransmitter GABA (gamma-aminobutyric acid) which is the major inhibitory neurotransmitter used to dampen and moderate the function and intensity of a wide range of other signal carriers in the brain.
Benzodiazepines, while not a GABA agonist, increase the impact of GABA at receptor sites, particularly the GABA-α receptors. This works to reduce the activity of a range of other neurotransmitters, in particular glutamate. This is similar to the way alcohol works, with benzodiazepines being much more selective and subtle in their effects. While alcohol acts on the brain like a blunt instrument, benzos are a much more refined and nuanced pharmacologic tool. Since benzos act in a roughly similar way to alcohol, the withdrawal from these substances shares similarities as well. Benzo withdrawal is more subdued and less dangerous than alcohol withdrawal in general, but both syndromes present great risk and intense discomfort.
While considered anxiolytics, benzos are also technically sedative-hypnotics that produce sedation, euphoria, lowered awareness, stress reduction, and muscle relaxation. Through prolonged use and/or taking very high doses of benzos, the brain will adapt to the presence of benzos by reducing sensitivity to GABA. This process is known as downregulation and it is an attempt of the brain to maintain neurotransmitter balance and protect itself from damage by reducing its responses to GABA. This causes tolerance to develop at first, and will eventually lead to dependence.
Once downregulation has occurred and benzo use is stopped, withdrawal symptoms will begin within hours to days. Since GABA has reduced impact in the brain due to downregulation, these withdrawal symptoms tend to manifest as opposites of the effects of benzos. Where benzos acted as a seizure suppressor, relaxant, nervous system depressant, and anxiety reducer, the symptoms of withdrawal will increase seizure risk, tension, stress, anxiety, and can produce several other issues that can be very serious.
Benzodiazepine withdrawal can be fatal if it is left untreated and unmonitored. Even detox does not guarantee a safe and relatively painless experience, it greatly increases the chances of a positive and less uncomfortable ordeal and outcome. The trained medical staff, medications, and psychiatric professionals at these detox centers will provide the most support possible to ease this difficult transition, and help someone build a solid foundation upon which to continue their recovery.
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