Clonazepam chemical structure
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Clonazepam

Clonazepam (marketed by Roche under the trade-name Klonopin® in the United States and Rivotril® in Canada and Europe) is a drug which is a benzodiazepine derivative. It is a highly potent and powerful sedative, hypnotic, anticonvulsant, amnestic and anxiolytic. more...

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Pharmacology

Like other benzodiazepines, clonazepam is believed to act by simulating the action of GABA on the central nervous system. Because of strong anxiolytic properties and euphoriant side-effects it is said to be among the class of 'highly potent' benzodiazepines with a higher risk of abuse, misuse and dependence than other benzodiazepines. The sedative effects of Clonazepam are relatively weak, compared to its strong anxiolytic and anticonvulsant effects. One quarter of a milligram (0.25mg) of Clonazepam is equivalent to five milligrams (5.00mg) of Diazepam.

Indications

Clonazepam is commonly prescribed for:

  • Epilepsy
  • Anxiety disorder
  • Panic attacks
  • Restless leg syndrome (RLS)
  • Inital treatment of mania, together with firstline-drugs such as lithium, haloperidol or risperidone
  • Hallucinogen persisting perception disorder (off-label use)
  • Chronic fatigue syndrome
  • Night terrors

Clonazepam is rarely used as a treatment for insomnia, because its sedative effects are relatively weak compared to other benzodiazepines.

Availability

Clonazepam was approved in the United States as a generic medication in 1997 and is now manufactured and marketed by several companies.

Clonazepam is available in the following forms:

  • Tablets: 0.25, 0.5, 1.0, and 2mg
  • Liquid concentrate: 2.5mg per ml
  • Oral wafers: 0.25, 0.5, 1.0 mg
  • Injection concentrate: 1mg per ml

Dosage

Epilepsy

Status epilepticus - 1mg is given slowly by I.V.; if seizures persist additional doses of 1mg may be given in intervals of 10 to 20 minutes.

Clonazepam can be useful for long-term treatment of some petit-mal forms of epilepsy in children and adolescents (adults may also respond well).

Up to 30% of epileptic patients treated with clonazepam develop a serious tolerance to the anticonvulsant effects. This may require dose increases or gradual withdrawal and replacement of the drug.

Oral doses in long term treatment of epilepsy vary from 1mg to 20mg, depending upon the severity of case and the weight of the patient. Treatment should be initiated at a low dose, and can be increased gradually if necessary.

Other

  • Anxiety and panic disorders - 1mg to 10mg daily, in divided doses
  • Restless Leg Syndrome - 1mg to 2mg at bedtime
  • Mania - Up to 20mg daily, in divided doses

Side Effects

Because Clonazepam can impair both mental and motor function, those taking it are advised to use caution when operating motor vehicles or machinery, or engaging in hazardous occupations requiring mental alertness. Side effects include:

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Clonazepam: An Effective Treatment Of Neurally Mediated Symptoms In Patients With Chronic Fatigue Syndrome - Abstract
From CHEST, 10/1/00 by Mumtaz Siddiqui

Mumtaz Siddiqui, MD; Nazih N Kadri, MD; Tom T Hee, MD(*); Karen S Rovang, MD; Timothy Ryan, RN; Daniel Hilleman, PhD; Aryan N Mooss, MD and Syed M Mohiuddin, MD. Cardiology, Creighton University School of Medicine, Omaha, NE.

PURPOSE: Clonazepam has been shown to be effective in the treatment of neurocardiogenic symptoms. However its role in the treatment of neurally mediated symptoms (NMS) in patients (pt) with chronic fatigue syndrome (CFS) has not been investigated.

METHODS: Thirteen pt (3 male, 10 female, age range 14-53 years) with diagnosed CFS and had associated NMS were referred to the Creighton University Cardiac Center. NMS included but were not limited to orthostatic presyncope (8/13 pt), weakness (13/13 pt), exercise intolerance (13/13 pt), and the inability to participate in day to day activity normal for age and gender (13/13 pt). NMS were reproduced by head up Tilt Table study (HUT) in 13/13 pt. Ten of 13 pt had abnormal HUT. These pt were given Clonazepam at 0.25 mg-0.75 mg/d (mean 0.41 mg/d).

RESULTS: Orthostatic presyncope episodes decreased from a daily occurrence to 0-2 episodes per month in 7/8 pt. Twelve of 13 pt had significant reduction of NMS and were able to resume normal lifestyles. Six of 10 pt had a normal response to HUT while 3/10 pt had significant improvement in HUT duration. One of 13 pt failed HUT and failed to have significant clinical improvement. Clonazepam side effects included initial early morning sedation in all pt. Late side effects included chest discomfort in one pt (noncardiac), and excessive sedation in 2 pt which subsided with dose reduction.

CONCLUSION: Clonazepam, a centrally acting medication, in a small well tolerated dose (0.25-0.75 mg /d) is clinically effective in the treatment of NMS occurring in pt with CFS. Prospective placebo controlled studies are needed to confirm these findings.

CLINICAL IMPLICATIONS: Therapy for neurocardiogenic syncope has traditionally included beta blockers, SSRIs, disopyramide, and volume expansion. Clonazepam can be added to the list of potentially useful drugs for neurocardiogenic syncope.

COPYRIGHT 2000 American College of Chest Physicians
COPYRIGHT 2001 Gale Group

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