individualized, especially in people who are elderly and debilitated in whom the risk of oversedation is greater. long-term therapy may lead to cognitive deficits, especially in the elderly, which may only be partially reversible. the elderly metabolize benzodiazepines more slowly than younger people and are more sensitive to the adverse effects of benzodiazepines compared to younger individuals even at similar plasma levels. additionally, the elderly tend to take more drugs which may interact or enhance the effects of benzodiazepines. benzodiazepines, including lorazepam, have been found to increase the risk of falls and fractures in the elderly. as a result, dosage recommendations for the elderly are about half of those used in younger individuals and used for no longer than two weeks. lorazepam may also be slower to clear in the elderly, leading potentially to accumulation and enhanced effects. lorazepam, similar to other benzodiazepines and nonbenzodiazepines, causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. falls and hip fractures are frequently reported. the combination with alcohol increases these impairments. partial, but incomplete, tolerance develops to these impairments. liver or kidney failure – lorazepam may be safer than most benzodiazepines in people with impaired liver function. like oxazepam, it does not require liver oxidation, but only liver glucuronidation into lorazepam-glucuronide. therefore, impaired liver function is unlikely to result in lorazepam accumulation to an extent causing adverse reactions. similarly kidney disease has minimal effects on lorazepam levels. surgical premedication – informed consent given only after receiving lorazepam premedication could have its validity challenged later. staff must use chaperones to guard against allegations of abuse during treatment. such allegations may arise because of incomplete amnesia, disinhibition, and impaired ability to process cues. because of its relatively long duration of residual effects (sedation, ataxia, hypotension, and amnesia), lorazepam premedication is best suited for hospital inpatient use. people should not be discharged from the hospital within 24 hours of receiving lorazepam premedication unless accompanied by a caregiver. they should also not drive, operate machinery, or use alcohol within this period. drug and alcohol dependence – the risk of abuse of lorazepam is increased in dependent people. comorbid psychiatric disorders also increase the risk of dependence and paradoxical adverse effects. tolerance and dependence dependence typified by a withdrawal syndrome occurs in about one-third of individuals who are treated for longer than four weeks with a benzodiazepine. higher doses and longer periods of use increase the risk of developing a benzodiazepine dependence. potent benzodiazepines with a relatively short half life, such as lorazepam, alprazolam, and triazolam, have the highest risk of causing a dependence. if regular treatment is continued for longer than four to six months, dose increases may be necessary to maintain effects, but treatment-resistant symptoms may in fact be benzodiazepine withdrawal symptoms. due to the development of tolerance to the anticonvulsant effects, benzodiazepines are generally not recommended for long-term use for the management of epilepsy. increasing the dose may overcome tolerance, but tolerance may then develop to the higher dose and adverse effects may persist and worsen. the mechanism of tolerance to benzodiazepines is complex and involves gabaa receptor downregulation, alterations to subunit configuration of gabaa receptors, uncoupling and internalisation of the benzodiazepine binding site from the gabaa receptor complex as well as changes in gene expression. the likelihood of dependence is relatively high with lorazepam compared to other benzodiazepines. lorazepam's relatively short serum half-life, its confinement mainly to blood, and its inactive metabolite can result in interdose withdrawal phenomena and next-dose cravings, that may reinforce psychological dependence. because of its high potency, the smallest lorazepam tablet strength of 0.5 mg is also a significant dose. to minimise the risk of physical/psychological dependence, lorazepam is best used only short-term, at the smallest effective dose. if any benzodiazepine has been used long-term, the recommendation is a gradual dose taper over a period of weeks, months or longer, according to dose and duration of use, the degree of dependence and the individual. coming off long-term lorazepam use may be more realistically achieved by a gradual switch to an equivalent dose of diazepam and a period of stabilization on this, and only then initiating dose reductions. the advantage of switching to diazepam is that dose reductions are felt less acutely, because of the longer half-lives (20–200 hours) of diazepam and its active metabolites. withdrawal on abrupt or overly rapid discontinuation of lorazepam, anxiety, and signs of physical withdrawal have been observed, similar to those seen on withdrawal from alcohol and barbiturates. lorazepam, as with other benzodiazepine drugs, can cause physical dependence, addiction, and benzodiazepine withdrawal syndrome. the higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. withdrawal symptoms can, however, occur from standard dosages and also after short-term use. benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regimen. rebound effects often resemble the condition being treated, but typically at a more intense level and may be difficult to diagnose. withdrawal symptoms can range from mild anxiety and insomnia to more severe symptoms such as seizures and psychosis. the risk and severity of withdrawal are increased with long-term use, use of high doses, abrupt or over-rapid reduction, among other factors. short-acting benzodiazepines such as lorazepam are more likely to cause a more severe withdrawal syndrome compared to longer-acting benzodiazepines. withdrawal symptoms can occur after taking therapeutic doses of lorazepam for as little as one week. withdrawal symptoms include headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia. it takes about 18–36 hours for the benzodiazepine to be removed from the body. the ease of physical dependence to lorazepam, (ativan brand was particularly cited), and its withdrawal were brought to the attention of the british public during the early 1980s in esther rantzen's bbc tv series that's life!, in a feature on the drug over a number of episodes. interactions lorazepam is not usually fatal in overdose, but may cause respiratory depression if taken in overdose with alcohol. the combination also causes greater enhancement of the disinhibitory and amnesic effects of both drugs, with potentially embarrassing or criminal consequences. some experts advise that people should be warned against drinking alcohol while on lorazepam treatment, but such clear warnings are not universal. greater adverse effects may also occur when lorazepam is used with other drugs, such as opioids or other hypnotics. lorazepam may also interact with rifabutin. valproate inhibits the metabolism of lorazepam, whereas carbamazepine, lamotrigine, phenobarbital, phenytoin, and rifampin increase its rate of metabolism. some antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opiates, antipsychotics and alcohol, when taken with lorazepam may result in enhanced sedative effects. overdose