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Anxiolytics and sedatives: dependence, symptoms and treatment
Medical expert of the article
Last reviewed: 04.07.2025
The use of anxiolytics, sedatives and hypnotics for medical reasons is widespread. Their use can result in intoxication, accompanied by physical and mental disorders. Repeated use can lead to abuse and dependence.
Distinct behavioral, emotional, and cognitive disturbances do not always develop even in regular users, depending on the dosage and pharmacodynamic effects of the drug. To a certain extent, there is cross-tolerance between alcohol, barbiturates, and non-barbiturate anxiolytics and sedatives, including benzodiazepines. (Barbiturates and alcohol are very similar in the dependence they cause, withdrawal symptoms, and chronic intoxication.) If the consumption of anxiolytics and sedatives decreases below a critical level, a self-terminating withdrawal syndrome develops.
[ Symptoms of Sedative Addiction
Poisoning (acute intoxication). Signs of progressive intoxication with anxiolytics and sedatives are suppression of superficial reflexes, fine nystagmus on gazing to the side, slightly increased excitability with coarse or rapid nystagmus, ataxia, slurred speech, instability in maintaining posture. Further progression is manifested by nystagmus on gazing forward, somnolence, marked ataxia with falls, confusion, deep sleep, constricted pupils, respiratory depression, and may ultimately lead to death. Patients taking large doses of sedatives often exhibit difficulty in the thinking process, slow speech and comprehension (along with some dysarthria), memory impairment, impaired judgment, narrowed focus, emotional lability.
Chronic use. In susceptible patients, psychological dependence on the drug may develop rapidly, even after several weeks of use; attempts to discontinue the drug result in insomnia, manifested by restlessness, restless sleep, frequent awakenings, and a feeling of tension in the morning. The degree of physical dependence is determined by the dose and duration of use; for example, phenobarbital at a dose of 200 mg/day taken for many months may not cause significant tolerance, but when taken at 300 mg/day for more than 3 months or 500-600 mg/day for 1 month, it may lead to withdrawal syndrome upon discontinuation.
Withdrawal from barbiturates taken in large doses causes an acute withdrawal syndrome in the form of a severe, life-threatening disorder resembling delirium tremens. Sometimes, even with proper withdrawal treatment, seizures occur for 1 to 2 weeks. During the first 12 to 20 hours after discontinuation of short-acting barbiturates, if untreated, the patient becomes increasingly restless and weakened, and tremors increase. Within 2 days, tremors become more noticeable, deep tendon reflexes may increase, and the patient becomes weaker. On the 2nd to 3rd day, 75% of patients taking >800 mg/day of barbiturates develop seizures, which can lead to status epilepticus and death. If untreated, between the 2nd and 5th day, withdrawal syndrome manifests itself as delirium, insomnia, confusion, threatening auditory and visual hallucinations. Hyperpyrexia and dehydration are common.
Withdrawal from benzodiazepines results in a similar withdrawal syndrome, although it is rarely severe or life-threatening. Onset may be slow because benzodiazepines persist in the body for a long time. Withdrawal of varying severity has been reported in people taking therapeutic doses, although the prevalence of this unusual phenomenon is unknown. Withdrawal may be more pronounced in those taking drugs with rapid absorption and rapid decline in serum concentrations (eg, alprazolam, lorazepam, triazolam). Many patients who abuse benzodiazepines also abuse alcohol, and alcohol withdrawal may occur when benzodiazepine withdrawal ceases.
Treatment for sedative addiction
Acute intoxication usually requires nothing more than observation. In some cases, respiratory support is required. The benzodiazepine receptor antagonist flumazenil can be used to treat severe sedation due to benzodiazepine overdose. Its clinical effectiveness is uncertain, as most patients with benzodiazepine overdose recover without treatment. Flumazenil has occasionally been associated with seizures when used to relieve sedation.
The treatment of dependence on sedatives, especially barbiturates, consists of tapering the drug according to a strict schedule and monitoring for withdrawal symptoms. Often the best option is to add a longer-acting compound that is easier to withdraw. Before initiating withdrawal, sedative tolerance should be assessed by testing with a test dose of phenobarbital 200 mg orally given to a non-intoxicated patient on an empty stomach; if the patient is intolerant, this dose produces drowsiness or light sleep within 1–2 h. Patients with moderate tolerance experience some sedation; patients with tolerance >900 mg show no signs of intoxication. If 200 mg is ineffective, tolerance can be clarified by repeating the test in 3–4 h with a higher dose. Marked anxiety and agitation may increase the patient's tolerance. The daily dose established with tolerance is usually given in four divided doses over 2-3 days to stabilize the patient's condition, and then tapered by 10% per day. Withdrawal should occur in a hospital. Once withdrawal has begun, it is difficult to return the condition to its previous level, but with careful monitoring, symptoms can be minimized. Restoration of CNS stability requires about 30 days.
Phenobarbital may be used as an alternative. It does not cause narcotic intoxication, unlike faster-acting substances. Fast-acting barbiturates, other sedatives, and weak anxiolytics may be replaced by a dose of phenobarbital equivalent to 1/3 of the average daily dose of the drug to which the patient is dependent; for example, for secobarbital 1000 mg/day, the stabilizing dose of phenobarbital is 300 mg/day, usually prescribed as 75 mg every 6 hours. Phenobarbital is given orally 4 times a day, and its initial dose is reduced by 30 mg/day until complete withdrawal. Since the initial dose is established on the basis of anamnestic information, there is a potential for error, so the patient should be carefully observed for the first 72 hours. If agitation or anxiety persists, the dose should be increased; If the patient is drowsy, dysarthric, or has nystagmus, the dose should be reduced. While the patient is undergoing detoxification, other sedatives and psychoactive drugs should be avoided. However, if the patient is taking antidepressants, especially tricyclics, the antidepressants should not be stopped abruptly; the dose should be reduced gradually over 3-4 days.