Benzodiazepines
Benzodiazepines are a class of psychoactive drugs known for their sedative and calming effects. Due to their rapid onset and quick symptom relief, they are often used for treating severe anxiety and insomnia. They are also effective at rapidly aborting convulsant activity in people with epilepsy or other seizure disorders.
There are different types of benzodiazepines, varying in their chemistry and duration of action. There are short-acting (<24 hours) and long-acting (>24 hours) substances. The most well-known benzodiazepines are diazepam, alprazolam, temazepam and nitrazepam.
Benzodiazepines were introduced into clinical use in the 1960’s with chlordiazepoxide, closely followed by diazepam (Valium). The introduction of benzodiazepines led to a revolution in the treatment of anxiety and insomnia, as they were significantly safer than barbiturates, the drug class they replaced.
Due to their calming and sedative effects, benzodiazepines became a target for abuse quickly after their release onto the market. Street names for benzodiazepines include “vallies”, “jellies”, “blues”, and “benzos”.
There is a wide range of medicines that belong to the benzodiazepine group. They vary in chemical structure, leading to differences in their sedative effects, in the time of life, in the dose and number of doses, in the administration mechanism, in the potency, and in the action onset. Some well known brand names are Xanax (alprazolam), Valium (diazepam), Klonopin (clonazepam), Ativan (lorazepam), Restoril (temazepam) and Librium (chlordiazepoxide).
In the clinical environment benzodiazepines are available as tablets, capsules, solution or emulsion for injection, oral suspension or solution and enema solution. They are administered via the oral, intravenous, intramuscular or rectal routes, depending on their desired effect.
Besides legally manufactured benzodiazepines, there have been detections of illegally manufactured benzodiazepines since 2007. Currently, there are 20 of these “new” benzodiazepines which have physiological and psychological effects, but have not been properly tested in clinical trials like licensed medicines.
Benzodiazepines quickly diffuse through the blood-brain barrier and primarily work by interacting with GABA-A receptors. These receptors are special proteins in the brain that help regulate nerve activity. They are activated by a chemical called gamma-aminobutyric acid (GABA), which is the main neurotransmitter responsible for calming down nerve signals in the central nervous system.
Benzodiazepines bind at a site that is distinct from the GABA binding site, increasing the affinity of GABA to the receptor and potentiating the response of the receptor to GABA. The potentiation of the effects of GABA, which works as a depressor on the central nervous system, causes sedative effects.
Because of their quick diffusion and influence on the inhibitory neurotransmitter GABA, benzodiazepines have rapid sedative effects, causing relaxation. This makes them attractive medications for those struggling with sleep and anxiety.
Benzodiazepines are used in general medicine, psychiatry, neurology, internal medicine, and in the field of anaesthesia, for the treatment of many clinical disorders.
Due to their sedative effects calming the nervous system, benzodiazepines are used short-term to treat sleep problems (hypnotics) and anxiety disorders (anxiolytics). They are also used to ease distress, panic, and fear.
Benzodiazepines also relax muscles and have anticonvulsant effects, which makes them useful in treating the withdrawal effects of alcohol, where they work to ease agitation as well as preventing seizures, muscle spasms and shaking. Due to this anticonvulsant effect, it can be used for people with epilepsy.
Benzodiazepines are preferred medicines for so many clinical disorders because of their fast state of action, efficiency, low number of collateral effects, and minimal acute toxicity in comparison to other medications. However, due to the risk of both mental and physical addiction, they are often not used long term.
Benzodiazepines calm the nervous system, which reduces anxiety, relaxes the mind and muscles, and decreases alertness and concentration. Common side effects are drowsiness, lethargy, and fatigue. Another common side effect is anterograde amnesia, which is the inability to form new memories after taking the drug. In higher doses, the sedative effects of benzodiazepines become stronger. They can then cause impaired motor coordination, dizziness, slurred speech, blurry vision and mood swings.
For some people, benzodiazepines can cause paradoxical or disinhibitory reactions. Characteristic symptoms are excessive talkativeness, increased activity level, excitement, agitation, aggression and confusion. Important risk factors for paradoxical effects are older age and dementia, but also history of alcohol use and affective disorder have been associated with a higher risk of paradoxical effects from benzodiazepines.
Benzodiazepines are considered relatively safe to use in the treatment of a variety of disorders. However, due to the development of tolerance, which causes users to need increasing doses for the same symptom relief, there is a severe potential for dependence. This is why benzodiazepines are usually not recommended to use for longer than four weeks.
When benzodiazepines are taken in high doses, they can cause unpleasant and potentially harmful effects. Overdosing can lead to slurred speech, dizziness, hostile or erratic behaviour, and impaired motor coordination. Impaired motor coordination can increase the risk of fall and injuries, and the risk of traffic accidents.
In more severe cases, overdosing can lead to depressed breathing and loss of consciousness. This can happen from benzodiazepines alone, but often arises from a combination with other sedatives like alcohol or opioids. Combining benzodiazepines and opioids increases the risk of non-fatal and fatal overdose, particularly due to respiratory depression.
As benzodiazepines can cause anterograde amnesia, which is the inability to form new memories after taking the drug, in combination with their sedative effects, they are commonly associated with drug-facilitated sexual assaults (DFSA).
In some cases, the use of benzodiazepines has been associated with a higher risk on suicide attempt and suicide. Benzodiazepines are known to increase impulsivity and aggression, traits that can lead to a dissociated type of aggression and impulsive actions that elevate the risk on suicidal behaviour. While benzodiazepines are useful for acute symptom relief in anxiety and insomnia, their potential to increase suicide risk calls for careful use, especially in patients with coexisting mental health issues.
Benzodiazepines carry increased risks for certain health conditions and patient groups. Individuals with COPD may face heightened risks due to respiratory suppression, while those with opioid use disorders have an elevated risk of (both intentional and unintentional) overdose.
Older adults are especially vulnerable, as benzodiazepines are linked to falls, hip fractures, delirium, and motor vehicle accidents. Additionally, people with liver or kidney disease may also be at risk, as their bodies struggle to break down and clear the drug, leading to potentially toxic buildup
During pregnancy, benzodiazepines reach the foetus by permeating the placenta, causing adverse effects. This includes delay in the growing process, sedation, inability to breastfeed, abstinence symptoms, extreme excitability and feeding difficulties. It is highly recommended to avoid the use of benzodiazepines during pregnancy, unless it is strictly necessary to treat anxiety.
Benzodiazepines are depressant of the central nervous system and can therefore have several interactions with other drugs and medications that work on that system.
Combining benzodiazepines with substances that are also central nervous system depressants, like alcohol and opioids, can be extremely dangerous. When taken together, they can amplify each other's effects, leading to a greater risk of severe sedation, respiratory depression, coma, or even death.
Combining benzodiazepines with stimulants like speed and cocaine carries different risks. The effects of the substances are opposite in many ways, as benzodiazepines are depressant drugs and stimulants have a stimulating effect on the central nervous system, leading to increased energy and alertness. Combining these opposing drugs can place intense strain on the body, as stimulants speed up physiological functions, while benzodiazepines slow them down. This can mask the effects of each drug, leading individuals to consume higher doses of one or both substances, increasing the risk of overdose.
One-off, occasional or short-term use of benzodiazepines is unlikely to result in the development of dependence. However, when the substance is being used for a longer period, users can develop a physical and psychological addiction. The main driving factor for dependence is the development of tolerance, as users need higher doses for the same symptom relief.
There are two main groups of people who develop benzodiazepine dependence. The first group consists of people who sought medical help during increased anxiety or sleeplessness, but continued using the medication beyond the recommended time-frame or at doses outside the recommended range. The second group consists of people actively seeking out the sedative effects of benzodiazepines, as benzodiazepine dependence is often accompanied by dependence on other substances and / or alcohol. In this case, benzodiazepines are abused to reduce the withdrawal effects of the other substances and to enhance or prolong the effects of the other substance.
Short-acting and high-potency benzodiazepines (like Xanax) are more addictive than long-acting benzodiazepines (like Valium). People who suffer from a substance use disorder are at higher risk of developing benzodiazepine dependence.
The harms of benzodiazepine addiction are in many ways similar to those of other substance addictions. It is characterised by a strong desire or sense of compulsion to take the substance, difficulty in controlling its use, tolerance to the use of the substance, neglect of alternative pleasures and interests and persistent use of the substance, despite harm to oneself and others.
When people have developed a dependence on benzodiazepine, they can suffer withdrawal symptoms similar to that of alcohol withdrawal when they stop taking the substances. These include both physical (pain, tension, spasm, tachycardia, seizure) and psychological (anxiety, depression, insomnia and depersonalisation) symptoms.
Abruptly stopping benzodiazepines can be dangerous, as the more severe withdrawal symptoms like seizures, require medical care. Someone with a physical and / or psychological dependence on benzodiazepines should seek supervision from a doctor to stop their use. An effective and safe way to stop benzodiazepine dependence usually consists of a combination of cognitive-behavioural therapy and a slow benzodiazepine taper through medication.
There are possible harms of long-term benzodiazepine use, although not everyone experiences these problems with long-term use.
Long-term use of benzodiazepines has been associated with psycho-cognitive impairments. The greatest deficits are in the areas of working memory, processing speed, divided attention, recent memory, and expressive language. After withdrawal, these impairments are likely, though not always, to persist.
Long-term use has also been associated with negative change in sleep microstructure in patients with insomnia, influencing the quality of sleep. The relationship between long-term benzodiazepine use and mood disorders is complex, but long-term use has been associated with chronic dysphoric mood, anxiety, depression and irritability. This may be because the brain and body become reliant on the substance’s anxiety-relieving effects.
Short-term, occasional medical or recreational use of benzodiazepines has a relatively low risk of harm. However, there are dangerous sides to the use of benzodiazepines, especially when they are mixed with other substances or when they are taken in higher doses or for longer periods than subscribed.
A first sign of the possible development of benzodiazepine dependence is when you start developing a tolerance for the substance’s effects. In order to avoid developing dependence, it is advised to not take benzodiazepines for longer than four weeks.
It is not advised to combine benzodiazepines with other substances. When you are mixing them, it is important to be aware of the potential risks. Combining benzodiazepines with substances that are also central nervous system depressants, like alcohol and opioids, can lead to a greater risk of severe sedation, respiratory depression, coma, or even death. Combining benzodiazepines with stimulants, like speed and cocaine, leads to a greater risk of taking high doses or overdosing, as the substances can mask each other’s effects.
When someone is overdosing on benzodiazepines it is important to help them, as overdosing can lead to depressed breathing and loss of consciousness. When you notice slower breathing or unconsciousness, there are a few things you should do:
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Place the person on their side so that their airway is not blocked if they vomit.
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Do not leave the person alone, as their condition might get worse.
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Monitor the person and if they a) become unresponsive; b) vomit while unconscious; or c) have slow breathing, make sure to call emergency services.
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Let the medical team know what the person has taken, if you know.
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