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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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AAN releases recommendations for managing essential tremor
From American Family Physician, 11/1/05 by Amber Huntzinger

The Quality Standards Subcommittee of the American Academy of Neurology (AAN) has released evidence-based recommendations for the initiation of pharmacologic and surgical therapies for patients with essential tremor. The recommendations are based on a systematic literature review and were rated for strength of evidence. The full report was published in the June 28, 2005, issue of Neurology and can be found online at http://www. neurology.org/cgi/content/full/64/12/2008.

Essential tremor is defined as the presence of postural and kinetic tremor. Classic essential tremor most commonly affects the upper limbs, but it also can affect a head, lower limbs, voice, tongue, face, and trunk. Although essential tremor does not reduce life expectancy, and symptoms are limited to tremors, the condition may cause substantial physical and psychosocial disability (e.g., difficulty with writing, drinking, eating, dressing, speaking, and other fine motor skills). Propranolol (Inderal) is the only drug approved by the U.S. Food and Drug Administration for the management of essential tremor. However, an estimated 30 percent of patients will not respond to this medication. Other drugs may be used, and surgical intervention is an invasive alternative to pharmacologic therapy.

Recommendations

PHARMACOLOGIC THERAPY

Table 1 summarizes the evidence for the pharmacologic management of essential tremor.

Level A. Propranolol was effective in managing limb tremor related to essential tremor. The results of treatment with once-daily, long-acting propranolol (Inderal LA) were similar to those of standard propranolol in managing limb tremors. Physicians might consider the use of propranolol, long-acting propranolol, or primidone (Mysoline) to manage limb tremor in patients with essential tremor, depending on concurrent medical conditions and potential side effects. Primidone and propranolol were equally effective for initial treatment of patients with limb tremor.

Trazodone (Desyrel) did not significantly affect postural or kinetic tremor and is not recommended for managing limb tremor.

Level B. Alprazolam (Xanax), atenolol (Tenormin), gabapentin (Neurontin) mono-therapy, sotalol (Betapace), and topiramate (Topamax) may reduce limb tremor associated with essential tremor. Atenolol, gabap-patient's entin monotherapy, sotalol, and topiramate may be used for limb tremor, although data are limited. Alprazolam should be used with caution because of the potential for abuse. Propranolol should be considered for the management of head tremor.

Acetazolamide (Diamox), isoniazid (INH), and pindolol (Visken) probably do not reduce limb tremor and are not recommended for managing essential tremor.

Level C. Nadolol (Corgard) and nimodipine (Nimotop) may be considered to manage limb tremor associated with essential tremor, but clonazepam (Klonopin) should be used with caution because of its potential for abuse and withdrawal symptoms. Clozapine (Clozaril) is recommended only for refractory cases of essential tremor because of the risk of agranulocytosis.

Methazolamide (Neptazane), mirtazapine (Remeron), nifedipine (Procardia), and verapamil (Calan) probably do not reduce limb tremor and are not recommended for managing essential tremor.

SURGICAL THERAPY

Table 2 summarizes the evidence for the surgical management of essential tremor. Surgical intervention should be considered only for patients who do not respond to pharmacologic therapy.

Level C. Sufficient evidence was available only on the effectiveness of chronic thalamic deep brain stimulation (DBS) and thalamotomy for managing essential tremor. Unilateral thalamotomy may be used to manage limb tremor, but bilateral thalamotomy is not recommended because of adverse effects. Thalamic DBS may be used to treat patients with limb tremor, but insufficient evidence exists to make a recommendation regarding its effectiveness in managing head and voice tremor. Although DBS has fewer adverse effects, physicians should choose between DBS and thalamotomy based on the patient's intraoperative complications compared with the practicality of the procedures.

Level U. gamma knife surgery, chronic thalamic DBS (head), chronic thalamic DBS (voice), and unilateral versus bilateral DBS (hand) should be considered unproven therapies at this time.

Conclusion

The committee concludes that research on the management of essential tremor is limited, and additional prospective, double-blind, placebo-controlled trials are needed to better determine the effectiveness and side effects of pharmacologic and surgical therapy for essential tremor.

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