Pregnancy Category D

Uses. This antianxiety drug is also known for its sedative properties and is used to promote sleep and to fight convulsions. The substance is given to treat status epilepticus, a dangerous condition in which people have one epileptic seizure after another, back-to-back. It can reduce and sometimes even eliminate vomiting from cancer chemotherapy. Lorazepam has been used to treat LSD and methamphetamine overdose and has been a standard medicine to help alcoholics through the alcohol withdrawal syndrome. Recreational sedative users report euphoria from lorazepam. When given experimentally in combination with other drugs, it has helped reduce depression. In contrast, experimentation using motion picture excerpts to evoke particular emotions found that lorazepam may reduce happy feelings and increase unhappy ones. One study found that lorazepam worked as well as alprazolam for treating panic attacks, and a case report tells of success in treating mania. Lorazepam has been used to cure both catatonia (in which people are frozen in place) and akathisia (compulsive moving around). Patients being prepared for surgery receive the drug to calm them and to cloud their memory of the event.

Lorazepam is 5 times stronger than diazepam and 15 times stronger than oxazepam, and one experiment showed that lorazepam is 370 to 783 times stronger than meprobamate in producing some effects, ranging from degraded performance in tests to amount of liking for one drug or the other.

Relatively little research seems to be done on whether members of different races respond differently to the same drug. This type of uncommon study has been done with lorazepam. The work found that although doses lasted about as long in young Americans as in young Japanese, a dose lasted about 20% longer in elderly Japanese than in elderly Americans—and a dose lasted about 20% longer in elderly Americans than in young Americans, so the difference became quite noticeable in Japanese subjects. ("American" and "Japanese" are nationalities, not races, but the research description stated that the issue of racial effect was being investigated; so those nationality labels were intended to have racial connotations.)

Drawbacks. Partial amnesia is a typical effect of the substance, and after using it for several days, people may have trouble gaining new memories. Investigators have also found that the drug interferes with detecting whether information is correct, while simultaneously reducing a person's awareness of memory trouble. Occasionally lorazepam temporarily stops respiration, and people suffering from serious breathing trouble should avoid the substance. The same goes for persons with acute narrow-angle glaucoma. The drug can reduce body temperature and, depending on circumstances in experiments, either raise or lower heart rate and blood pressure.

Researchers find that the substance interferes with recognizing common items shown in distorted pictures; such trouble is considered evidence of the brain suffering from weakened ability to understand what the eyes see. A case report notes that lorazepam may impede movements of the mouth and face. The drug somewhat garbles speech. Because of adverse impact on mental clarity and physical performance, people are advised to avoid operating dangerous machinery (such as cars) for at least 48 hours after using lorazepam. Driving tests have shown the drug to reduce vehicle control skill while increasing risk-taking. Other tests demonstrate worsened attention, slower reaction time, and delay in reasoning out the solution to a problem. An experiment demonstrated that users may be unaware of how much the drug is interfering with their abilities. Dizziness and weakness may occur. Typically a dose has greater impact on the elderly, and all persons risk falling down until the drug wears off. A case report notes that lorazepam can eliminate a person's interest in sexual activity. An unusual case report tells of someone who was hearing noises in an ear, and the noises became musical hallucinations of popular songs when the person began taking lorazepam. More typically, however, the drug is able to stop auditory hallucinations. Other case reports tell of visual hallucinations after taking the compound, and that response was also observed in 3 children among 112 who were given the drug. Although lorazepam is used to reduce anxiety, case reports and formal experimentation show that the substance can increase aggressiveness (perhaps because people are less afraid to do things). A schizophrenic who received the drug lost enough inhibitions to start acting out violent impulses, and similar reports exist. In formal experimentation volunteers receiving lorazepam became more aggressive but did not realize they were angrier than other persons in the experiment.

Abuse factors. Various psychological tests measure how much a drug appeals to someone. Among persons who already have a history of drug abuse (a population prone to like drugs much more than nonusers do), some results indicate lorazepam has about the same addictive potential as diazepam or meprobamate; some results simply show lorazepam to have an unspecified amount of appeal; and in one experiment abusers found the drug about as attractive as a placebo (indicating low addictive potential). Rats begin exhibiting tolerance to lorazepam after several days of dosing. If a person takes lorazepam enough to develop dependence on it, suddenly quitting the drug can produce a withdrawal syndrome. If drug use has been heavy the withdrawal can include confusion, depression, perspiration, cramps, tremors, vomiting, mania, and convulsions. Lighter use can produce lighter withdrawal such as insomnia and generally feeling out of sorts. Symptoms can be avoided altogether if a person gradually takes smaller and smaller doses rather than stopping abruptly.

Drug interactions. Lorazepam generally makes people more susceptible to effects of alcohol. If a person taking lorazepam simultaneously ingests other depressants (alcohol, barbiturates, opiates) the total depressant effects deepen. Although we might expect stimulants to counteract lorazepam's actions, research has found that cocaine can boost some of them, with sleepiness becoming particularly greater. Thus cocaine users receiving lorazepam for medical treatment may require lower doses than normal.

Cancer. Mice and rat studies have not yielded evidence that lorazepam causes cancer.

Pregnancy. In mice lorazepam increases incidence of eyelid malformation and cleft palate. Mice having fetal exposure to lorazepam exhibit lasting neu-rochemistry abnormalities, and rats with fetal exposure demonstrate brain difficulty. Extrapolating from rat test results, two researchers concluded that fetal exposure to the drug may result in male offspring having more anxiety than normal and females having less than normal. Pregnant rabbits receiving lorazepam in an experiment produced more birth defects than usual. Persuasive evidence indicates that the drug passes from a pregnant woman into the fetus. The drug is not recommended for pregnant women unless the need is dire. Analysts examining thousands of medical records concluded that lorazepam does not necessarily cause birth defects but found that the drug may be involved with a deformity blocking an infant's anal opening. Fetal exposure to lorazepam is suspected of slowing development of infants' abilities to move and think. Case reports say that infants can have withdrawal symptoms if the mother used the drug during pregnancy, symptoms accompanied by abnormal muscle tone and trouble with eating. Nursing mothers are told to avoid lorazepam, as infants might be drugged from the amount of lorazepam that passes into milk.

Additional scientific information may be found in:

Bond, A., and M. Lader. "Differential Effects of Oxazepam and Lorazepam on Aggressive Responding." Psychopharmacology 95 (1988): 369-73. Funderburk, F.R., et al. "Relative Abuse Liability of Lorazepam and Diazepam: An Evaluation in 'Recreational' Drug Users." Drug and Alcohol Dependence 22 (1988): 215-22.

"Lorazepam." In Therapeutic Drugs, C. Dollery. 2d ed. New York: Churchill Livingstone, 1999. L98-L100. O'Hanlon, J.F., et al. "Anxiolytics' Effects on the Actual Driving Performance of Patients and Healthy Volunteers in a Standardized Test. An Integration of Three Studies." Neuropsychobiology 31 (1995): 81-88. Schweizer, E., et al. "Lorazepam vs. Alprazolam in the Treatment of Panic Disorder."

Pharmacopsychiatry 23 (1990): 90-93. Shader, R.I., et al. "Sedative Effects and Impaired Learning and Recall after Single Oral Doses of Lorazepam." Clinical Pharmacology and Therapeutics 39 (1986): 526-29.

Continue reading here: Chemical Abstracts Service Registry Number 50373 Formal Names Lysergic Acid Diethylamide

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