Clonazepam is a benzodiazepine derivative with highly potent anticonvulsant, muscle relaxant, and anxiolytic properties. It is marketed by Roche under the trade-names Klonopin in the United States, and Ravotril in Chile. Other names like Rivotril or Rivatril are known throughout the large majority of the rest of the world. Clonazepam is a chlorinated derivative of nitrazepam and therefore a nitrobenzodiazepine.
Indications
Clonazepam may be prescribed for
- Epilepsy
- Anxiety disorders
- Panic disorder
- Initial treatment of mania or acute psychosis together with firstline drugs such as lithium, haloperidol or risperidone
- Hyperekplexia
- Bruxism
- Restless legs syndrome
- Rapid eye movement behavior disorder
- Hallucinogen persisting perception disorder
- The treatment of acute and chronic akathisia
- Use as a muscle relaxant (off-label use)
- Use as a sedative for sleep (off-label use). Its long half-life sometimes makes it useful for treating middle-of-the-night insomnia (waking up too early) but may also lead to next-day effects.
- Essential tremor (off-label use)
- Can also be used to relax bladder neck tightness to improve symptoms of benign prostatic hyperplasia (BPH).
In the treatment of acute epilepsy via intravenous administration approximately 72.5 percent of patients show improved EEG patterns, 17.5 percent show no improvement and for 10 percent of patients clonazepam has a paradoxical effect and worsens EEG readings.
Clonazepam is sometimes used for refractory epilepsies; however, long-term prophylactic treatment of epilepsy has considerable limitations, the most notable ones being the loss of antiepileptic effects due to tolerance, which renders the drug useless with long-term use, and side-effects such as sedation, which is why clonazepam and benzodiazepines as a class should, in general, be prescribed only for the acute management of epilepsies.
Clonazepam or diazepam has been found to be effective in the acute control of nonconvulsive status epilepticus. However, the benefits tended to be transient in many of the patients, and the addition of phenytoin for lasting control was required in these patients.
In general, Clonazepam has been found to be ineffective in the control of infantile spasms. Clonazepam is less effective and potent as an anticonvulsant in bringing infantile seizures under control compared with nitrazepam in the treatment of West syndrome, which is an age-dependent epilepsy affecting the very young. However, as with other epilepies treated with benzodiazepines, long-term therapy becomes ineffective with prolonged therapy, and the side effects of hypotonia and drowsiness are troublesome with clonazepam therapy; other antiepileptic agents are, therefore, recommended for long-term therapy, possibly Corticotropin (ACTH) or vigabatrin. Furthermore, Clonazepam is not recommended for widespread use in the management of seizures related to West syndrome.
Clonazepam has been used in the management of seizure disorders in children and also for infantile spasms. However, usefulness of clonazepam is limited due to its dose-limiting side effects, especially its negative effect on cognition.
Clonazepam has shown itself to be highly effective as a short-term (3 weeks) adjunct to SSRI treatment in obsessive-compulsive disorder and clinical depression in reducing SSRI side effects with the combination being superior to SSRI treatment alone in a study funded by the manufacturers of clonazepam, Hoffman LaRoche Inc.
Availability
Clonazepam was approved in the United States as a generic drug in 1997 and is now manufactured and marketed by several companies.
Clonazepam is available in the U.S. as tablets (0.5, 1.0, and 2 mg) and orally disintegrating tablets (wafers) (0.125, 0.25, 0.5, 1.0, and 2 mg). In other countries, clonazepam is usually available as tablets (0.5 and 2 mg), orally disintegrating tablets (0.25, 0.5, 1 and 2 mg) oral solution (drops, 2.5 mg/mL), as well as solution for injection or intravenous infusion, containing 1 mg clonazepam per ampoule (e.g. Rivotril inj.).
Side-effects
- Drowsiness
- Impairment of cognition, judgment, or memory
- Irritability and aggression
- Psychomotor agitation
- Lack of motivation
- Loss of libido
- Impaired motor function
- Impaired coordination
- Impaired balance
- Dizziness
- Diarrhea
- Cognitive Impairments
- Increased Sleepwalking (If used in treatment of sleepwalking)
- Auditory Hallucinations
- Short-term memory loss
- Anterograde amnesia (common with higher doses)
- Some users report hangover-like symptoms of being drowsy, having a headache, being sluggish, and being irritable after waking up if the medication is taken before sleep. This is likely the result of the medication's long half-life, which continues to affect the user after waking up, as well as its disruption of the REM cycle.
- Serious dysphoria
- Thrombocytopenia
- Serious psychological and psychiatric side-effects
- Induction of seizures or increased frequency of seizures
- Personality changes
- Behavioural disturbances
- Psychosis
- Incontinence
- Liver damage
- Paradoxical behavioural disinhibition (most frequently in children, the elderly, and in persons with developmental disabilities)
- Rage
- Excitement
- Impulsivity
The long term effects of clonazepam can include; depression, disinhibition and sexual dysfunction.
- Anxiety, irritability, insomnia
- Panic attacks, tremor
- Seizures similar to delirium tremens (with long-term use of excessive doses)
Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus, but, when used for longer periods of time, serious side-effects may develop, such as interference with cognitive functions and behavior. Many individuals treated on a long-term basis develop a form of dependence known as "low-dose dependence," as was shown in one double-blind, placebo-controlled study of 34 therapeutic low-dose benzodiazepine users — physiological dependence was demonstrated via flumazenil-precipitated withdrawal. Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side-effects) of the drug. Side-effects of the drug itself are generally benign, but sudden withdrawal after long-term use can cause severe, even fatal, symptoms.
Tolerance and withdrawal
Like all benzodiazepines, clonazepam is a benzodiazepine receptor agonist.
Tolerance
Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently. Chronic use of benzodiazepines leads to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy. Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long term effectiveness as an anticonvulsant.
Withdrawal
Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. Sudden withdrawal may also induce the potentially the life threatening condition status epilepticus. Antiepileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced slowly and gradually when discontinuing the drug to reduce withdrawal effects. Carbamazepine has been trialed in the treatment of clonazepam withdrawal and has been found to be ineffective in preventing clonazepam withdrawal status epilepticus from occurring.
Special precautions
Caution in the elderly. Increased risk of impairments, falls and drug accumulation. Benzodiazepines also require special precaution if used in the pregnancy, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.
Caution in children. Clonazepam is not recommended for use in those under 18. Use in very young children may be especially hazardous. Of anticonvulsant drugs behavioural disturbances occur most frequently with clonazepam and phenobarbital.
Caution using high dosages of clonazepam. Doses higher than 0.5 – 1 mg per day are associated with significant sedation.
Clonazepam may aggravate hepatic porphyria.
Caution in chronic schizophrenia. A 1982 double blinded placebo controlled study found clonazepam increases violent behavior in individuals with chronic schizophrenia.
Interactions
Clonazepam decreases the levels of carbamazepine, and likewise its l
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