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Benzodiazepine is a group of medicinal substances which have sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, muscle relaxant and amnesic action. Benzodiazepine's cross the blood-brain barrier and primarily act on the central nervous system (CNS), where they affect brain function. Post traumatic Stress Disorder (PTSD) is aDead Link Removed, and symptoms often include anxiety and insomnia. As such, Benzodiazepine's are frequently prescribed to patients who suffer with PTSD. A Selective Serotonin reuptake inhibitor is likely to be the best choice of pharmacotherapy for many patients with any type of panic disorder, but Benzodiazepine's are also often used, and some studies suggest that these medications are still used with greater frequency than the SSRI's.
Mode of Action
Benzodiazepine's are so called because their core chemical structure is the fusion of a benzene ring and a diazepine ring.
Benzodiazepine's effect the neurotransmitter GABA (gamma-aminobutyric acid)and it's receptors to reduce the signals flowing through the CNS. This reduces the communication between neurons and therefore has a calming effect on many of the functions of the brain. Each Benzodiazepine differs in their length of action on the brain (their "elimination half-life"), and as such they are classified into either short-, intermediate- or long-acting. Short- and intermediate-acting Benzodiazepine's are preferred for the treatment of insomnia; longer-acting Benzodiazepine's Link Removed for the treatment of anxiety. The effects of Benzodiazepine's are often compared to that of alcohol, since Ethanol (alcohol) also enhances the effects of GABA.
The first Benzodiazepine, Chlordiazepoxide (Librium), was discovered by accident in 1955. Initial poor experimental results meant that the substance was not tested until 1957, when it was found to have sedative properties. But, probably the best known of all Benzodiazepine's is Diazepam , which was marketed by Hoffmann–La Roche under the brand name Valium in 1963. The introduction of Benzodiazepine's led to a decrease in the prescription of barbiturates, and by the 1970s they had largely replaced the older drugs for sedative and hypnotic uses.
Most Benzodiazepine's are administered orally, especially when taken for anxiety or insomnia; however, they can also be given intravenously, intramuscularly or rectally.
List of Benzodiazepine's
There are many, many Benzodiazepine's available, and it is beyond the scope of this article to name them all, but here is a list of the most common ones.
Benzodiazepine's are used to treat many different symptoms, including anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a pre-medication for medical or dental procedures. Antidepressants can also be helpful for people with anxiety disorders, however Benzodiazepine's start to work much faster than antidepressants.
Short-term use of Benzodiazepine's is generally considered to be safe, although dis-inhibition has been reported, similar to the dis-inhibition associated with alcohol. i.e. saying and doing things you would normally not do, or that are not considered socially accepted due to a lack of restraint caused by the Benzodiazepine (or alcohol).
Long-term use of Benzodiazepine's is extremely controversial, due to decreased efficacy over long term use - "tolerance", (which means the patient requires an increasingly higher dose to reach the same affect), and also physical "dependence", which leads to "withdrawal effects", when the drug is stopped.
For these reason, in the UK, and generally accepted world wide, Anxiolytic Benzodiazepine treatment should be limited to the lowest possible dose for the shortest possible time. Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders.
Dosage
The recommended dosage is dependent on the type of Benzodiazepine prescribed, and the severity of the symptoms. Dosages may be different for different people. It’s important to take the drug as prescribed by the Doctor.
Contraindications
Common side effects include:
People can build a tolerance to Benzodiazepine's if they are taken over a long period of time and may need higher and higher doses to get the same effect. Some people may become dependent on them. To avoid these problems, doctors usually prescribe the medication for short periods, a practice that is especially helpful for people who have substance abuse problems or who become dependent on medication easily. If people suddenly stop taking Benzodiazepine's, they may get withdrawal symptoms, or their anxiety may return. Therefore, they should be tapered off slowly.
Addiction to Benzodiazepine's is a common occurrence, so they should only be taken with caution and knowledge. Benzodiazepine's are now recognized as major drugs of abuse and addiction, as such they are bought and sold illegally on the black market. The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits, depression and anxiety. Despite repeated recommendations to limit Benzodiazepine's to short-term use (2–4 weeks), doctors worldwide are still prescribing them for months or years. This over-prescribing has resulted in large populations of long-term users who have become dependent on Benzodiazepine's.
Clinical Trials
Most types of psychotropic drugs have been tried in the treatment of chronic posttraumatic stress disorder (PTSD), but have yielded limited results. Theory and retrospective research predict that early treatment may be more efficacious. Specifically, high-potency Benzodiazepine's have been recommended for the treatment of acute responses to trauma and for prevention of PTSD. A trial was conducted but, the results did not quantify expectations. "Contrary to expectations, the early administration of Benzodiazepine's to trauma survivors with high levels of initial distress did not have a salient beneficial effect on the course of their illness, while reducing physiologic expression of arousal."
During treatment discontinuation, new symptoms may emerge and anxiety may return, preventing many patients from successfully discontinuing their treatment. One study investigated the efficacy of cognitive behavioral therapy for patients with panic disorder who were attempting to discontinue treatment with high-potency Benzodiazepine's. The results showed that cognitive-behavioral interventions aided Benzodiazepine discontinuation for patients with panic disorder. In that 77% of the patients in the cognitive-behavioral program successfully discontinued Benzodiazepine treatment and remained Benzodiazepine free after a 3 month follow-up evaluation, compared to 25% for the patients receiving the slow taper program alone.
Mode of Action
Benzodiazepine's are so called because their core chemical structure is the fusion of a benzene ring and a diazepine ring.
Benzodiazepine's effect the neurotransmitter GABA (gamma-aminobutyric acid)and it's receptors to reduce the signals flowing through the CNS. This reduces the communication between neurons and therefore has a calming effect on many of the functions of the brain. Each Benzodiazepine differs in their length of action on the brain (their "elimination half-life"), and as such they are classified into either short-, intermediate- or long-acting. Short- and intermediate-acting Benzodiazepine's are preferred for the treatment of insomnia; longer-acting Benzodiazepine's Link Removed for the treatment of anxiety. The effects of Benzodiazepine's are often compared to that of alcohol, since Ethanol (alcohol) also enhances the effects of GABA.
The first Benzodiazepine, Chlordiazepoxide (Librium), was discovered by accident in 1955. Initial poor experimental results meant that the substance was not tested until 1957, when it was found to have sedative properties. But, probably the best known of all Benzodiazepine's is Diazepam , which was marketed by Hoffmann–La Roche under the brand name Valium in 1963. The introduction of Benzodiazepine's led to a decrease in the prescription of barbiturates, and by the 1970s they had largely replaced the older drugs for sedative and hypnotic uses.
Most Benzodiazepine's are administered orally, especially when taken for anxiety or insomnia; however, they can also be given intravenously, intramuscularly or rectally.
List of Benzodiazepine's
There are many, many Benzodiazepine's available, and it is beyond the scope of this article to name them all, but here is a list of the most common ones.
- Diazepam (Valium), Several uses: short-term use in anxiety or insomnia; adjunct in acute alcohol withdrawal; status epilepticus; febrile convulsions; muscle spasm; peri-operative use
- Clonazepam (Klonopin), which is used for social phobia and General Anxiety Disorder (GAD)
- Lorazepam (Ativan), which is used for panic disorder
- Alprazolam (Xanax), which is used for panic disorder and GAD.
- Nitrazepam (Mogadon), which is used for insomnia (short term use)
- Flurazepam (Dalmane), which is used for insomnia (short term use)
- Loprazolam, which is used for insomnia, but is shorter acting than Nitrazepam
- Temazepam, which is used for insomnia, but is shorter acting than Nitrazepam
Benzodiazepine's are used to treat many different symptoms, including anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a pre-medication for medical or dental procedures. Antidepressants can also be helpful for people with anxiety disorders, however Benzodiazepine's start to work much faster than antidepressants.
Short-term use of Benzodiazepine's is generally considered to be safe, although dis-inhibition has been reported, similar to the dis-inhibition associated with alcohol. i.e. saying and doing things you would normally not do, or that are not considered socially accepted due to a lack of restraint caused by the Benzodiazepine (or alcohol).
Long-term use of Benzodiazepine's is extremely controversial, due to decreased efficacy over long term use - "tolerance", (which means the patient requires an increasingly higher dose to reach the same affect), and also physical "dependence", which leads to "withdrawal effects", when the drug is stopped.
For these reason, in the UK, and generally accepted world wide, Anxiolytic Benzodiazepine treatment should be limited to the lowest possible dose for the shortest possible time. Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders.
Dosage
The recommended dosage is dependent on the type of Benzodiazepine prescribed, and the severity of the symptoms. Dosages may be different for different people. It’s important to take the drug as prescribed by the Doctor.
Contraindications
- Hepatic impairment - Benzodiazepine's can precipitate coma if used in hepatic impairment.
- Renal impairment - Patients with renal impairment have increased cerebral sensitivity to Benzodiazepine's; start with small doses in severe impairment.
- Pregnancy -There is a risk of neonatal withdrawal symptoms when Benzodiazepine's are used during pregnancy. Avoid regular use and use only if there is a clear indication such as seizure control. High doses administered during late pregnancy or labor may cause neonatal hypothermia, hypotonia, and respiratory depression.
- Breast-feeding - Benzodiazepine's are present in milk, and should be avoided if possible during breast-feeding.
- Respiratory depression
- Marked neuromuscular respiratory weakness including unstable myasthenia gravis
- Acute pulmonary insufficiency
- Sleep apnoea syndrome
Common side effects include:
- Drowsiness and lightheadedness the next day
- Confusion and ataxia (especially in the elderly). Ataxia is a lack of muscle co-ordination.
- Amnesia may occur
- Dependence
- Headache
- Vertigo
- Hypo-tension
- Salivation changes
- Gastro-intestinal disturbances
- Visual disturbances
- Dysarthria (speech problems)
- Tremor
- Changes in libido
- Incontinence
- Urinary retention
- Blood disorders and jaundice reported
- Skin reactions
- On intravenous injection, pain, thrombophlebitis, and rarely apnoea
People can build a tolerance to Benzodiazepine's if they are taken over a long period of time and may need higher and higher doses to get the same effect. Some people may become dependent on them. To avoid these problems, doctors usually prescribe the medication for short periods, a practice that is especially helpful for people who have substance abuse problems or who become dependent on medication easily. If people suddenly stop taking Benzodiazepine's, they may get withdrawal symptoms, or their anxiety may return. Therefore, they should be tapered off slowly.
Addiction to Benzodiazepine's is a common occurrence, so they should only be taken with caution and knowledge. Benzodiazepine's are now recognized as major drugs of abuse and addiction, as such they are bought and sold illegally on the black market. The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits, depression and anxiety. Despite repeated recommendations to limit Benzodiazepine's to short-term use (2–4 weeks), doctors worldwide are still prescribing them for months or years. This over-prescribing has resulted in large populations of long-term users who have become dependent on Benzodiazepine's.
Clinical Trials
Most types of psychotropic drugs have been tried in the treatment of chronic posttraumatic stress disorder (PTSD), but have yielded limited results. Theory and retrospective research predict that early treatment may be more efficacious. Specifically, high-potency Benzodiazepine's have been recommended for the treatment of acute responses to trauma and for prevention of PTSD. A trial was conducted but, the results did not quantify expectations. "Contrary to expectations, the early administration of Benzodiazepine's to trauma survivors with high levels of initial distress did not have a salient beneficial effect on the course of their illness, while reducing physiologic expression of arousal."
During treatment discontinuation, new symptoms may emerge and anxiety may return, preventing many patients from successfully discontinuing their treatment. One study investigated the efficacy of cognitive behavioral therapy for patients with panic disorder who were attempting to discontinue treatment with high-potency Benzodiazepine's. The results showed that cognitive-behavioral interventions aided Benzodiazepine discontinuation for patients with panic disorder. In that 77% of the patients in the cognitive-behavioral program successfully discontinued Benzodiazepine treatment and remained Benzodiazepine free after a 3 month follow-up evaluation, compared to 25% for the patients receiving the slow taper program alone.
