Pregnancy Category D

Uses. Clonazepam is considered one of the more powerful benzodiazepine class drugs. Primary medical uses are against some kinds of convulsions, particularly in certain kinds of epilepsy, and against panic attacks. For persons suffering from panic attacks, measurements indicate the drug improves both quality of life and work productivity. The drug is also used as an antidepres-sant and to treat anxiety, catatonia, obsessive-compulsive disorder, the manic phase of manic-depressive behavior, and social phobia in general. A two-year follow-up study of persons receiving brief clonazepam treatment for social phobia found their improvement to be sustained after dosage stopped, and at the two-year mark they were doing better than a control group that had received a placebo. Clonazepam is sometimes preferred over alprazolam in treating anxiety because that condition seems less likely to reappear between doses of clonazepam than between doses of alprazolam. Clonazepam can be substituted for alprazolam in order to withdraw persons who have dependence with the latter drug. Clonazepam has been used to fight tics and also to treat muscle control diseases such as akathisia and tardive dyskinesia. Among children with attention deficit hyperactivity disorder (ADHD) who also have tics, a study found clonazepam could help suppress tics without harming the psychiatric effect of ADHD medicine. Although clonazepam is not a multiple sclerosis medicine, it is administered to relieve the affliction's symptoms. Clonazepam has helped reduce fainting spells. It is prescribed to relieve insomnia and to reduce a disorder in which sleeping persons thrash about. The substance has promoted cure of sleepwalking, including a documented extreme case in which a sleeping person would drive a car and engage in violence involving knives. The drug can relieve pain caused by jaw trouble and has been given to cancer patients to reduce vomiting from chemotherapy. Clonazepam and the antimania medicine lithium have been experimentally administered together as a successful treatment for cluster headaches. Clonazepam has eased burning mouth syndrome, a self-descriptive sensation that can persist for years. The drug has been used experimentally with limited success to treat ringing in the ears.

Drawbacks. Clonazepam is not recommended for persons suffering from narrow-angle glaucoma. The compound may worsen respiratory disease. The substance increases saliva production. It often makes people tired, interferes with muscular coordination, and can impede decision making; such effects hinder ability to operate dangerous machinery. Dozens of less common adverse effects are described, ranging from skin rash to painful gums. One case report concludes that clonazepam may promote porphyria, a body chemistry disorder that can make a person violent and supersensitive to light, but such a result is virtually unheard of. A review of medical records of men being treated for posttraumatic stress disorder suggested that the drug may commonly inhibit sexual performance in such a population. Some persons suffer from a disquieting affliction called apnea in which they temporarily stop breathing; case reports say clonazepam can cause apnea attacks. An experiment noted a rebound effect when people stop taking the drug for insomnia, meaning the condition is not cured but instead returns worse than ever, at least for awhile.

Contrary to normal expectations, the drug has occasionally been reported to bring on mania and even aggression. One case report noted that if panic attacks act as a warning against certain behavior, clonazepam's ability to reduce or eliminate panic attacks can also remove a person's inhibitions against the behavior. A small study suggests that clonazepam may reduce inhibitions in children, and case reports exist about the same effect in children, teenagers, and adults. Researchers curious about whether clonazepam especially reduces inhibitions examined medical records of 323 persons institutionalized for psychiatric disturbance, a population in which such a clonazepam effect might be particularly evident; although the study was not designed to demonstrate cause and effect, the records were consistent with a low risk of reduced inhibition from clonazepam and other benzodiazepine class drugs.

Abuse factors. Clonazepam has a withdrawal syndrome similar to alcohol's: cramps and tremors, convulsions, hallucinations, and general mental distress. The syndrome can be avoided if a person reduces dosage gradually. Suddenly halting the drug after taking it for an extended period of time can cause epileptic seizures.

Drug interactions. Clonazepam's actions can be boosted by alcohol, barbiturates, opiates, tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs). A case report suggests that effects may also be boosted by the heart medicine amiodarone. Another case report indicates that clonazepam reduces blood levels of the epilepsy medicine phenytoin. Taking clonazepam with the antidepressant paroxetine is suspected of causing a dangerous reaction called serotonin syndrome, a serious condition which can involve confusion, tremors, and high body temperature. Combining clonazepam with the antimania medicine lithium is suspected of causing muscular discoordination, including muscles used for speech. A case report noted delirium brought on by simultaneously taking clonazepam and the schizophrenia medicine clozapine.

Cancer. Not enough scientific information to report.

Pregnancy. No increase in birth defects was noted when pregnant rats and mice received many times the recommended human dose while embryos were in the organ-forming stage. Pregnant rabbits receiving clonazepam during the same stage, however, have produced offspring with birth defects such as limb malformations and cleft palate. Because other drugs in the benzodiazepine class are assumed to have potential for causing human birth defects, clona-zepam is considered inadvisable for pregnant women unless they and their physicians have considered the issue. Among 51 infants whose mothers took clonazepam during pregnancy, almost 10% had "major malformations"; although that small sample did not compare outcomes in matched women who took no such drug, the study's finding nonetheless raises a caution. A much larger study said that clonazepam taken in combination with other epilepsy drugs increased the chance of birth defects but said nothing about using clona-zepam alone. Clonazepam may disturb fetal heartbeat. Offspring with fetal exposure may be sedated, show poor muscle tone, and have low body temperature. Infants can be born with dependence to the drug. Clonazepam passes into human milk at levels high enough to affect infants, and breastfeeding mothers are counseled to avoid clonazepam.

Additional scientific information may be found in:

Cohen, L.S., and J.F. Rosenbaum. "Clonazepam: New Uses and Potential Problems."

Journal of Clinical Psychiatry 48 (1987, Suppl.): 50-56. Commander, M., S.H. Green, and M. Prendergast. "Behavioural Disturbances in Children Treated with Clonazepam." Developmental Medicine and Child Neurology 33 (1991): 362-63.

Davidson, J.R., and G. Moroz. "Pivotal Studies of Clonazepam in Panic Disorder."

Psychopharmacology Bulletin 34 (1998): 169-74. Davidson, J.R., et al. "Treatment of Social Phobia with Clonazepam and Placebo." Journal of Clinical Psychopharmacology 13 (1993): 423-28. Morishita, S., S. Aoki, and S. Watanabe. "Clonazepam as a Therapeutic Adjunct to Improve the Management of Psychiatric Disorders." Psychiatry and Clinical Neurosciences 52 (1998): 75-78. Rosenbaum, J.F., G. Moroz, and C.L. Bowden. "Clonazepam in the Treatment of Panic Disorder with or without Agoraphobia: A Dose-Response Study of Efficacy, Safety, and Discontinuance." Journal of Clinical Psychopharmacology 17 (1997): 390-400.

Worthington, J.J., III, et al. "Long-term Experience with Clonazepam in Patients with a Primary Diagnosis of Panic Disorder." Psychopharmacology Bulletin 34 (1998): 199-205.

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