Benzodiazepines: misuse of benzodiazepines

Benzodiazepines belong to those medicines that are particularly widely used throughout the world. They are mainly used to treat anxiety disorders and insomnia. Despite widespread use, targeted abuse of benzodiazepines is relatively rare. To date, there are conflicting data on the development of tolerance to the therapeutic effect of benzodiazepines and the emergence of withdrawal symptoms with a sudden discontinuation of their admission. If benzodiazepine is taken within a few weeks, then tolerance only develops in a small proportion of patients, so there is no problem with stopping the drug if the need for its use has disappeared. When taking the drug for several months, the proportion of patients who develop tolerance increases, and with a decrease in dose or withdrawal of the drug, abstinence syndrome may occur. At the same time it is difficult to distinguish the withdrawal syndrome from the re-occurrence of symptoms of anxiety, for which benzodiazepines were prescribed. Some patients eventually increase the dose of the drug taken, as they develop tolerance to its sedative effect. Many patients and their doctors, nevertheless, believe that the anxiolytic effect of the drugs persists even after the development of tolerance to the sedative effect. Moreover, these patients continue to take the drug for many years, following medical instructions, and there is no need to increase the dose, and they themselves are able to function effectively as long as the reception of benzodiazepine is continued. Thus, it remains unclear whether tolerance develops in the anxiolytic action of benzodiazepines. According to some reports, pronounced tolerance does not develop for all the effects of benzodiazepines, since the adverse effect on memory that occurs with "acute" administration of the drug is also reproduced in patients taking benzodiazepines for years.

[1], [2], [3], [4]

Symptoms of abstinence syndrome with benzodiazepine withdrawal

• Anxiety, agitation
• Sleep Disorders
• Dizziness
• Epileptic seizures
• Increased sensitivity to light and sound
• Paresthesia, unusual sensations
• Muscle spasms
• Myoclonic twitching
• Delirium

The American Psychiatric Association has formed an expert committee to develop recommendations for the correct use of benzodiazepines. Intermittent use - only with the appearance of the corresponding symptoms - prevents the development of tolerance and, therefore, preferable to daily use. Since patients with an alcoholic or other history-related addiction have a higher risk of developing benzodiazepine abuse, this category of patients should avoid the appointment of benzodiazepines on an ongoing basis.

Only a small proportion of patients taking benzodiazepines for medical reasons begin to abuse these drugs. At the same time, there are people who deliberately take benzodiazepines to get a "buzz". Among people who abuse benzodiazepines, the most popular drugs are those with a rapid onset of action (eg, diazepam or alprazolam). These individuals sometimes feign illnesses and force doctors to prescribe the drug or receive it through illegal channels. In most large cities, illegal distributors can buy benzodiazepines for $ 1-2 per tablet. With uncontrolled admission, the dose of drugs can reach very significant values, which is accompanied by the development of tolerance to their sedative effect. Thus, diazepam is usually prescribed to patients in a dose of 5-20 mg / day, while those who abuse the drug take it at a dose of up to 1000 mg / day and do not experience a significant sedative effect.

Persons abusing benzodiazepines can combine them with other drugs to obtain the desired effect. For example, they often take diazepam 30 minutes after taking methadone; as a result, they experience "high", which can not be achieved with the help of one of the drugs. Although there are cases when illegally used benzodiazepine is the main drug, it is most often used by persons dependent on other substances to reduce the side effects of their main substance or withdrawal syndrome upon discontinuation of its administration. For example, patients with cocaine dependence often take diazepam to alleviate the irritability and agitation caused by cocaine, and those with opioid dependence use diazepam and other benzodiazepines to relieve withdrawal symptoms if they fail to obtain the drug they prefer in time.

Barbiturates and other non-benzodiazepine sedatives

The use of barbiturates and other non-benzodiazepine sedatives in recent years has declined significantly due to the fact that new generation drugs proved to be more effective and safe. With abuse of barbiturates, many of the same problems arise as with the abuse of benzodiazepines, and their correction is similarly done.

Since the drugs of this group are often prescribed as sleeping pills to patients with insomnia, doctors should be aware of the potential danger of such treatment. Insomnia rarely has a primary character, except when it is associated with a short-term stressful situation. Sleep disorders are often a symptom of a chronic illness (eg, depression) or a regular age-related change in the need for sleep. The use of sedatives can adversely affect the structure of sleep, and in the subsequent lead to the development of tolerance to this effect. If you stop taking sedatives, you may experience a ricochet insomnia, which is more severe than before treatment. Such medically induced insomnia requires detoxification with a gradual decrease in dose of drugs.

[5], [6], [7], [8]

Medication intervention

If patients who take benzodiazepines for a long time as directed by a doctor wish to discontinue treatment, the gradual dose reduction process may take several months. Detoxification in this case can be done on an outpatient basis; Symptoms may occur, but in most cases they are easy enough. If symptoms of anxiety increase again, then non-benzodiazepine agents, for example, buspirone, can be used, but it is usually inferior in effectiveness to benzodiazepines in this category of patients. Some experts recommend for the period of detoxification to transfer the patient to long-acting benzodiazepine, for example, clonazepam. In a similar situation, other drugs are recommended, for example, anticonvulsants carbamazepine and phenobarbital. Controlled studies that compare the effectiveness of different treatments have not been conducted. Since patients who have taken low doses of benzodiazepines for many years usually do not notice any side effects, the doctor and the patient must decide together whether detoxification or switching to another anxiolytic sense makes sense.

When an overdose or to stop the action of long-acting benzodiazepines used in general anesthesia, a specific antagonist of the benzodiazepine receptors flumazenil can be used. It is also used to arrest persistent manifestations of withdrawal symptoms when discontinuing the use of long-acting benzodiazepines. It is believed that flumazenil is able to restore the functional state of receptors that have been long-term stimulated with benzodiazepine, but this assumption is not supported by the data of the studies.

In persons intentionally abusing benzodiazepines, detoxification should usually be performed in a hospital setting. Abuse of benzodiazepines is often part of the combined dependence on alcohol, opioids or cocaine. Detoxification can be a complex clinical and pharmacological problem requiring knowledge of the pharmacological and pharmacokinetic characteristics of each of the substances. Reliable anamnestic data may be absent, sometimes not so much because the patient is insincere with the doctor, but because he really does not know what substance he received from the seller on the street. Preparations for detoxification should not be prescribed according to the principle of a "cookbook" - their dose should be determined by careful titration and monitoring the patient's condition. For example, abstinence syndrome with discontinuation of benzodiazepine may become apparent only in the second week of hospitalization, when the patient develops an epileptic seizure.

The combined dependence

In the complex process of detoxification in patients who are dependent on opioids and sedatives, the general rule is that the patient should first stabilize the patient's opioids with methadone, and then focus on more dangerous manifestations of sedation withdrawal. The dose of methadone depends on the degree of opioid dependence. The trial dose is usually 20 mg, then it is adjusted depending on the patient's condition. Opioid detoxification can be initiated after the issue with more dangerous substances has been resolved. Long-acting benzodiazepine (eg, diazepam, clonazepam or clorazepate) or long-acting barbiturate (eg, phenobarbital) can be used to stop the sedative withdrawal syndrome. The dose is selected individually by assigning a series of trial doses and monitoring their effect with determining the level of tolerability. In most cases, the combined detoxification procedure can be performed in 3 weeks, but in some patients who abuse large doses of psychoactive substances or who have comorbid psychiatric disorders, longer treatment is needed. After detoxification, the prevention of relapse requires a long-term outpatient rehabilitation program, as in the treatment of alcoholism. No specific drugs have been found that would be useful in the rehabilitation of persons dependent on sedatives. At the same time, it is clear that specific mental disorders, such as depression or schizophrenia, require appropriate treatment.