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About one-third of individuals who take benzodiazepines for longer than four weeks become dependent and experience withdrawal syndrome on cessation.Differences in rates of withdrawal (50–100%) vary depending on the patient sample.It is also used as a premedication for inducing sedation, anxiolysis, or amnesia before certain medical procedures (e.g., endoscopy).
Dose increases may overcome the effects of tolerance, but tolerance may then develop to the higher dose and adverse effects may increase.
The mechanism of tolerance to benzodiazepines includes uncoupling of receptor sites, alterations in gene expression, down-regulation of receptor sites, and desensitisation of receptor sites to the effect of GABA.
Withdrawal symptoms can sometimes resemble pre-existing conditions and be misdiagnosed.
Diazepam may produce less intense withdrawal symptoms due to its long elimination half-life.
Patients with severe attacks of apnea during sleep may suffer respiratory depression (hypoventilation), leading to respiratory arrest and death.
Diazepam in doses of 5 mg or more causes significant deterioration in alertness performance combined with increased feelings of sleepiness.
Additionally, after cessation of benzodiazepines, cognitive deficits may persist for at least six months; it is unclear whether these impairments take longer than six months to abate or if they are permanent.
Benzodiazepines may also cause or worsen depression.
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