Pronunciation: al-PRAY-zoh-lam (also pronounced al-PRAZ-oh-lam)

Chemical Abstracts Service Registry Number: 28981-97-7

Formal Names: Alplax, Frontal, Solanax, Tafil, Trankimazin, Xanax, Xanor, Zotran

Type: Depressant (benzodiazepine class). See page 21

Federal Schedule Listing: Schedule IV (DEA no. 2882)

USA Availability: Prescription

Pregnancy Category: D

Uses. This calming and sleep-inducing substance is probably the most frequently prescribed drug in the benzodiazepine class. Alprazolam is used mainly to help persons suffering from panic attacks and other anxiety disorders, but it is not recommended for posttraumatic stress disorder. The compound can dramatically lessen premenstrual syndrome (PMS) and is routinely given to women of child-bearing age. Improvement of PMS is not invariable, however, and two careful experiments yielded results showing little benefit. Theoretical reasons and results from a rat experiment suggest that alprazolam may help maintain bone mass. That action may be especially important to athletes and elderly women, who commonly suffer loss of bone mass—an affliction making breakage easier. The drug has been tested as an asthma treatment with encouraging results, though reasons for success are unclear. Some researchers believe the drug has potential in diabetes control. In an experiment measuring alprazolam's pain-relieving properties, the drug reduced the severity but not the frequency of chronic tension headaches. The compound has antidepressant and anticonvulsant properties, has been used to treat ringing in the ears and to alleviate tremors and catatonia, and has been found useful in easing alcohol withdrawal symptoms in alcoholics. A rat study suggests that alprazolam may also have a place in treating cocaine addiction. Measurements find the drug worsens snoring but improves quality of sleep (at least for the snorers).

Drawbacks. Motorists have suffered accidents attributed to drowsiness from alprazolam. Experiments show that the drug reduces startle response in humans, which may mean drivers are less alert or respond less vigorously to situations. Case reports tell of alprazolam (alone and in combination with other medicine) causing the skin to become extra sensitive to sunlight. The compound may produce jaundice.

Although the drug normally encourages eating, about 20% of persons in one study experienced weight loss, along with unwanted effects such as difficulty in controlling muscles (including urinary incontinence), peevishness, bellicosity, and lowering of inhibitions. Researchers generally believe the drug interferes with sexual function in men and women. A case report tells of the drug causing mania with euphoria, high self-confidence, increased energy, and trouble with getting proper sleep—all rather untypical effects. Despite such possibilities, one team reviewing scientific literature found reports of unwanted actions to be uncommon for alprazolam, and another team concluded that alprazolam generally has fewer such reports than other benzodi-azepine class drugs. Analysts who examined medical records of 10,895 alprazolam patients found little mention of unwanted effects. In evaluating the infrequent accounts of mania, aggression, hallucinations, or other unexpected psychological reactions to alprazolam, we should remember that many such cases involve persons already exhibiting psychiatric disturbances for which they are receiving the drug. Such reactions may be far less likely in a psychiatrically normal person.

Abuse factors. An experiment showed no tendency for abuse of alprazolam among users even though it is a controlled substance. A 1993 review of human and animal studies of the drug concluded that scientific experimental evidence failed to support a popular belief that abuse of alprazolam was more likely than abuse of other benzodiazepine class drugs. Another 1993 report disagreed but described alprazolam abuse as minuscule and limited to persons already misusing other drugs, particularly opiates and alcohol. Brainwave and other measurements imply that alprazolam has more appeal to alcoholic men than it does to nonalcoholics. Experiments show that persons with a family history of alcoholism tend to experience more pleasure (even euphoria) when taking alprazolam than do persons lacking such a history. Tests find the drug to have stronger effects (positive and negative) on women whose fathers were alcoholics, compared to women whose immediate family background does not include alcoholism. When experiments gave drug abusers a choice between diazepam or alprazolam, the abusers tried both but found alprazolam more pleasant.

Craving and tolerance do not seem to develop, but alprazolam can produce bodily dependence, which is a traditional sign of addictive potential. Sudden stoppage can cause seizures or delirium, so practitioners customarily wean their patients with tapering dosages. Withdrawal symptoms may include perspiration, tremors, cramps, vomiting, diarrhea, cloudy eyesight, prickling sensations on the skin, and general befuddlement. Convulsions and seizures are reported. One experiment noted that withdrawal signs cleared up in a week.

Drug interactions. Kava is an intoxicating drink prepared from the kava plant, suspected of interacting so seriously with alprazolam that a coma may result. Persons taking antifungus drugs such as itraconazole or ketoconazole are supposed to avoid alprazolam, as those two drugs increase the power and prolong the effect of an alprazolam dose. The heartburn medicine cimetidine (Tagamet), the antidepressant fluoxetine (Prozac), and the pain-relieving opioid propoxyphene each lengthen the time an alprazolam dose lasts, and ritonavir (used against the human immunodeficiency virus in AIDS [acquired immunodeficiency syndrome]) can drastically boost the potency of alprazolam. In contrast, alprazolam's effects are reduced by the epilepsy drugs phe-nytoin and carbamazepine, by the tuberculosis medicine rifampin, and by the asthma medication theophylline. A case of glaucoma resulting in blindness is attributed to a multidrug regimen of antidepressants and antianxiety medicines including alprazolam. Some tests find that the substance worsens reaction time and memory. Taking alprazolam with diazepam can cause persons to forget what happened while they were under the drugs' influence. In one experiment alprazolam by itself seemed to interfere with memory even weeks after taking it, but deeper analysis of the results caused investigators to question any long-lasting effect. Persons functioning adequately while drinking alcohol decline in performance when a dose of alprazolam is added, and the combination may increase hostile attitudes and actions. Findings in a mice experiment showed alprazolam boosting pain relief provided by morphine, but a human experiment found no such increase (although alprazolam reduced the typical nausea effect of morphine—a benefit that has also been demonstrated in cancer chemotherapy patients). Alprazolam has cross-tolerance with chlordiazepoxide.

Cancer. A two-year rat experiment found no evidence that alprazolam causes cancer. Measurements of persons receiving alprazolam for panic disorder indicated the substance does not reduce levels of tumor necrosis factor-alpha, a protein that helps the body fight off cancer.

Pregnancy. Alprazolam experimentation with mice yielded no birth defects. Examination of pregnancies in which women used the drug during the first trimester found no more birth defects than would be expected if the drug were not taken at all, but researchers cautioned that the sample sizes (411 in one study and about 200 in another) were too small to reach firm conclusions about the drug's effect on fetal development. A study of 88 infants born to women who used alprazolam during pregnancy found 10 born with "major" deformities. Mice having prenatal exposure to the drug show reduced social interaction, and males are more aggressive than normal. Such mice also exhibit subtle trouble with hind legs.

Clinicians have observed alprazolam to increase the hormone that prepares female breasts for milk production. When combined with the pain reliever tramadol and the antidepressant citalopram, alprazolam has been known to cause excessive milk flow. Alprazolam passes into milk, and nursing is not recommended for mothers taking the drug. In one case an infant even exhibited drug withdrawal symptoms when a nursing mother who was receiving alprazolam ceased nursing.

Additional scientific information may be found in:

Edwards, J.G. "Prescription-Event Monitoring of 10,895 Patients Treated with Alprazolam." British Journal of Psychiatry 158 (1991): 387-92. Jonas, J.M., and M.S. Cohon. "A Comparison of the Safety and Efficacy of Alprazolam versus Other Agents in the Treatment of Anxiety, Panic, and Depression: A Review of the Literature." Journal of Clinical Psychiatry 54 (1993, Suppl.): 25-45. Nishith, P., et al. "Brief Hypnosis Substitutes for Alprazolam Use in College Students:

Transient Experiences and Quantitative EEG Responses." American Journal of Clinical Hypnosis 41 (1999): 262-68.

Romach, M.K. et al. "Characteristics of Long-Term Alprazolam Users in the Community." Journal of Clinical Psychopharmacology 12 (1992): 316-21.

Rothschild, A.J. "Comparison of the Frequency of Behavorial Disinhibition on Alprazolam, Clonazepam, or No Benzodiazepine in Hospitalized Psychiatric Patients." Journal of Clinical Psychopharmacology 20 (2000): 7-11.

Rush, C.R., et al. "Abuse Liability of Alprazolam Relative to Other Commonly Used Benzodiazepines: A Review." Neuroscience and Biobehavorial Reviews 17 (1993): 277-85.

Sellers, E.M., et al. "Alprazolam and Benzodiazepine Dependence." Journal of Clinical Psychiatry 54 (1993, Suppl.): 64-75.

Spiegel, D.A. "Efficacy Studies of Alprazolam in Panic Disorder." Psychopharmacology Bulletin 34 (1998): 191-95.

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