Oxazepam (Anxiolit, Serax, Serenid D)

Pronunciation: ox-A-zeh-pam (also pronounced ox-AZ-eh-pam)
Chemical Abstracts Service Registry Number: 604-75-1
Formal Names: Anxiolit, Serax, Serenid D
Type: Depressant (benzodiazepine class).
Federal Schedule Listing: Schedule IV (DEA no. 2835)
USA Availability: Prescription
Pregnancy Category: C

Uses.
This substance is a metabolite of diazepam, temazepam, chlordiazepoxide, and clorazepate dipotassium. Oxazepam’s primary medical usage is to fight insomnia, hostility, and anxiety. Some researchers have found the drug also works against depression, and the drug is used often for patients in mental health treatment centers. Studies show oxazepam, diazepam, and flunitrazepam to have about the same therapeutic effects, though not the same strengths (oxazepam being the weakest). In the 1990s a survey of pharmacies in Cracow, Poland, illustrated oxazepam’s worldwide popularity; around 14% of benzodiazepine prescriptions were for oxazepam, predominantly to women. One advantage of the drug is its safe “therapeutic ratio,” meaning that the amount needed to produce a desired medical effect is far below the amount needed to produce a poisonous effect. Thus medical practitioners have considerable flexibility in adjusting dosage to an exact amount needed by a patient.

Experimental use against tinnitus (ringing in the ears) has been promising. Sometimes oxazepam is the preferred antianxiety medicine for alcoholics suffering from cirrhosis, because a fully functioning liver is unnecessary to flush the substance from the body. Oxazepam is used to alleviate alcohol withdrawal syndrome and has been used to treat neuroses and schizophrenia.

Oxazepam is considered appropriate for short-term treatment of agitation in elderly persons suffering from dementia. Tests indicate the drug can reduce hostility as well as anxiety, an ability that would set oxazepam apart from other benzodiazepines. In a cat experiment, however, the drug increased predator behavior. The drug makes mice more combative. Rats kill more mice when dosed with oxazepam, but researchers interpret that result as illustrating potency of the drug rather than indicating it would promote aggression in humans. Human oxazepam reactions that increase hostility and combativeness are unusual and unexplained, although factors may include size and frequency of dose along with inherent personalities of users. Hostile human reactions are “paradoxical” effects, meaning they are the opposite of what normally happens after taking an oxazepam dose.

Drawbacks.
While under the drug’s influence people exhibit memory trouble. Oxazepam lowers body temperature in mice and rats. Case reports tell of oxazepam causing blisters or other skin eruptions on people. In mice the substance boosts the poisonous action of the cancer medicine ifosfamide. Some experiments using oxazepam to induce sleep find no hangover effect on persons’ performance the next day, but that result is not invariable; size of dose appears relevant. An experiment testing the drug’s effect on vigilance (an important ability when driving a car) found normal ability while persons were under the influence of a low dose. Another experiment using a dose four times greater did find vigilance impairment. Still another experiment showed slower movements.

Abuse factors.
One reviewer of the drug’s characteristics reported that it may have less addictiveness than diazepam. In one study opiate addicts found oxazepam no more attractive than a placebo. In another study sedative abusers judged the drug less attractive than diazepam and indeed mistakenly identified oxazepam as a placebo one third of the time (a mistake they almost
never made with diazepam) and even considered a placebo more appealing than oxazepam about one fifth of the time (a preference never occurring with diazepam). A similar experiment in which drug abusers compared oxazepam, diazepam, and placebo produced comparable results.

An animal research study found no tolerance produced by the drug. Monkeys, however, exhibit signs of tolerance, dependence, and withdrawal after taking the drug for a week or two. One human study found tolerance but no withdrawal symptoms. Nonetheless, melancholy, mood swings, confusion, anxiousness, panic, and seizures have been observed when doses of the drug stopped abruptly. Some of those “withdrawal symptoms,” however, are also conditions for which the drug is prescribed; so emergence of those conditions upon stopping the drug may simply mean the underlying conditions were not cured. A case report recounts a rare instance of someone having visual hallucinations while undergoing oxazepam withdrawal. Tapering oxazepam does not necessarily prevent abstinence symptoms, but symptoms have been controlled by substituting another drug. One authority warns that stopping oxazepam can be as touchy as stopping barbiturates. In the 1980s a health official in Australia portrayed oxazepam dependence as a growing problem. In contrast, another authority reviewing oxazepam’s history for a medical journal found only four accounts of human dependence on the drug and declared withdrawal symptoms to be unusual upon sudden stoppage. This reviewer speculated that oxazepam’s slow delivery of drug effects and its tendency to make people dizzy if a lot is consumed help discourage abuse.

Drug interactions.
A driving skills test showed that oxazepam worsens impairment induced by alcohol. Cigarette smoking shortens the time span that an oxazepam dose stays in the body. A mouse study found that animals could withstand higher doses of morphine and methadone if oxazepam was also
used.

Cancer.
Findings about oxazepam’s potential for causing human cancer have been inconclusive. Gene mutations would be a possible sign that cancer might eventually emerge; some laboratory tests show that the drug does not cause gene mutations, but genetic mutations were apparent after a six-month administration of the drug to mice. Oxazepam is described as causing liver cancer in mice. Researchers testing the drug on rats concluded that an unclear potential for causing cancer exists, but their uncertain conclusion was partly based on some dosages so high that apparently they were fatal to various individual animals.

Pregnancy.
Experiments have exposed mice to oxazepam during fetal development, and assorted differences in their behavior (compared to mice with no exposure) have been documented, including decreased sociability and decreased interaction with surroundings. What those differences might mean in a human context is unclear. Experimental evidence indicates that prenatal exposure to oxazepam may harm a mouse’s learning ability and temporarily slow growth. In humans the drug passes from a pregnant woman into the fetus. A survey of 4,014 instances of birth defects in the Netherlands from 1981 to 1994 found an association between oxazepam and cleft lip. The same association was found in Finland a few years earlier. Mice experiments have also produced head and mouth malformations, but the doses involved were
far higher than humans would be expected to take.

Oxazepam is considered to have less impact than other benzodiazepines on a nursing mother’s milk supply. Two nursing mothers who had measurable levels of oxazepam in their blood had no evidence of the substance in their milk. A case report tells of a nursing mother whose milk contained about 4.7% of her oxazepam dosage, with no apparent effect on the infant. In other cases, not even 0.001% of the oxazepam dose taken by a mother passed into her milk.

Additional scientific information may be found in:
Ayd, F.J., Jr. “Oxazepam: Update 1989.” International Clinical Psychopharmacology 5
(1990): 1–15.

Bliding, A. “The Abuse Potential of Benzodiazepines with Special Reference to Oxazepam.”
Acta Psychiatrica Scandinavica. Supplementum, no. 274 (1978): 111–16.

Bucher, J.R., et al. “Toxicity and Carcinogenicity Studies of Oxazepam in the Fischer
344 Rat.” Toxicological Sciences 42 (1998): 1–12.

Fouks, L., et al. “The Clinical Activity of Oxazepam.” Acta Psychiatrica Scandinavica.
Supplementum, no. 274 (1978): 99–103.

Griffiths, R.R., et al. “Comparison of Diazepam and Oxazepam: Preference, Liking and
Extent of Abuse.” Journal of Pharmacology and Experimental Therapeutics 229
(1984): 501–8.

Mewaldt, S.P., M.M. Ghoneim, and J.V. Hinrichs. “The Behavioral Actions of Diazepam
and Oxazepam Are Similar.” Psychopharmacology 88 (1986): 165–71.

Vaisanen, E., and E. Jalkanen. “A Double-Blind Study of Alprazolam and Oxazepam
in the Treatment of Anxiety.” Acta Psychiatrica Scandinavica 75 (1987): 536–41.