Topical formulations of lorazepam, while used as treatment for nausea especially in people in hospice, ought not be used in this form and for this purpose as they have not been proven effective. History
Historically, lorazepam is one of the "classical" benzodiazepines. Others include diazepam, clonazepam, oxazepam, nitrazepam, flurazepam, bromazepam, and clorazepate. Lorazepam was first introduced by Wyeth Pharmaceuticals in 1977 under the brand names Ativan and Temesta. The drug was developed by D.J. Richards, president of research. Wyeths original patent on lorazepam is expired in the United States. Society and culture
Recreational use
Lorazepam is also used for other purposes, such as recreational use, wherein the drug is taken to achieve a high, or when the drug is continued long-term against medical advice.A large-scale, nationwide, U.S. government study of pharmaceutical-related emergency department visits by SAMHSA found sedative-hypnotics are the pharmaceuticals most frequently used outside of their prescribed medical purpose in the United States, with 35% of drug-related emergency department visits involving sedative-hypnotics. In this category, benzodiazepines are most commonly used. Males and females use benzodiazepines for nonmedical purposes equally. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drugs, with 26% of attempted suicides involving them. Lorazepam was the third-most-common benzodiazepine used outside of prescription in these ER visit statistics. Legal status
Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S. and internationally under the United Nations Convention on Psychotropic Substances. It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada.
After four to six months of regular benzodiazepine use, evidence of continued efficacy declines.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. Lorazepams 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.