Sedative Dependence

The therapeutic benefits of sedatives are well-established; however, their effectiveness in controlling anxiety and stress is the main reason for their frequent use and misuse. Thus, dependence on sedatives is not an uncommon problem in everyday clinical practice. As a result, all sedatives can lead to both physical and psychological dependence, even when taken at therapeutic doses.

One of the consequences of sedative dependence is withdrawal syndrome when their administration is discontinued. Chronic stimulation of receptors with these drugs can suppress the endogenous production of neurotransmitters; therefore, removal of the drug can trigger clinically apparent counter-regulatory effects.

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Principles of tolerance, dependence, and withdrawal

Ingesting large doses of sedatives may not show predictable effects in individuals who chronically use them. The reason for this is tolerance, which is defined as the progressive decline in drug effect with repeated administration, necessitating greater doses of the drug to achieve the same effect.

Tolerance ensues when adaptive neural and receptor changes, which, taken together, are referred to as neural plasticity, arise as a consequence of repeated exposures. The most important changes that are encountered are downregulation, desensitization, and structural changes of the receptors. Furthermore, cross-tolerance is also observed among the sedatives.

A large number of sedatives are associated with drug dependence after chronic exposure, although the risk varies among them. For example, benzodiazepines are known to produce less euphoria when compared to other tranquilizers; thus, the risk of dependence is relatively low. In addition, this class of sedatives does not cause nearly as much metabolic tolerance as compared to barbiturates, nor do they affect rapid eye movement (REM) sleep extensively.

Still, both tolerance and withdrawal symptoms can develop following chronic benzodiazepine exposure. Symptoms can include abnormally rapid heart rate and breathing, overresponsive reflexes, tremors, confusion, and seizures. The severity and frequency of these symptoms are related to the dose, duration of the administration, and drug elimination rate.

Opioid withdrawal syndrome is similar to a severe flu and is usually characterized by sneezing, rhinorrhea, nausea, diarrhea, as well as cramps in the legs and abdomen. On the other hand, alcohol withdrawal symptoms can range from simple tremor to delirium tremens, with severe nervous system changes.

Xanax - One of the Most Abused Sedatives

Patient stabilization

Potentially dependent users of sedative drugs necessitate initial stabilization of their status, which should be followed by appropriate tolerance testing. If a patient appears to be tolerant, a long-acting sedative, such as diazepam or phenobarbital, should be used to induce withdrawal.

Due to its rapid absorption and distribution, diazepam is the drug of choice for stabilization and tolerance testing. During its chronic administration, diazepam is metabolized to desmethyldiazepam, which is a long-acting metabolite that makes this drug a perfect choice for a tapered withdrawal schedule.

Opioid dependence can be demonstrated by the naloxone test. Additionally, detoxification in withdrawal syndrome can be carried out in an outpatient, residential, or inpatient setting using opioid agonists, such as methadone, or certain non-opioid drugs, such as clonidine.


Further Reading

Last Updated: May 23, 2021

Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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