Clonazepam; Uses, Dosage, Side Effects, Interactions, Pregnancy

Clonazepam is an anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures.

Clonazepam, is a medication used to prevent and treat seizures, panic disorder, and for the movement disorder known as akathisia including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures .It is seldom effective in generalized tonic-clonic or partial seizures.

Mechanism of Action of Clonazepam

Clonazepam acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons. This further results in an inhibition of synaptic transmission across the central nervous system. Allosteric interactions between central benzodiazepine receptors and gamma-aminobutyric acid (GABA) receptors potentiate the effects of GABA. As GABA is an inhibitory neurotransmitter, this results in increased inhibition of the ascending reticular activating system. Benzodiazepines, in this way, block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

Benzodiazepines do not have any effect on the levels of GABA in the brain.Clonazepam has no effect on GABA levels and has no effect on gamma-aminobutyric acid transaminase. Clonazepam does, however, affect glutamate decarboxylase activity. It differs from other anticonvulsant drugs it was compared to in a study.Clonazepam’s primary mechanism of action is the modulation of GABA function in the brain, by the benzodiazepine receptor, located on GABA_A receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing. Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABA_Areceptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA’s inhibitory effects and resultant central nervous system depression.In addition, clonazepam decreases the utilization of 5-HT (serotonin) by neurons and has been shown to bind tightly to central-type benzodiazepine receptors.Because clonazepam is effective in low milligram doses (0.5 mg clonazepam = 10 mg diazepam), it is said to be among the class of “highly potent” benzodiazepines. The anticonvulsant properties of benzodiazepines are due to the enhancement of synaptic GABA responses, and the inhibition of sustained, high-frequency repetitive firing.Benzodiazepines, including clonazepam, bind to mouse glial cell membranes with high affinity. Clonazepam decreases release of acetylcholine in the feline brain and decreases prolactin release in rats.Benzodiazepines inhibit cold-induced thyroid? stimulating hormone (also known as TSH or thyrotropin) release. Benzodiazepines acted via micromolar benzodiazepine binding sites as Ca²⁺ channel blockers and significantly inhibit depolarization-sensitive calcium uptake in experimentation on rat brain cell components. This has been conjectured as a mechanism for high-dose effects on seizures in the studyClonazepam is a chlorinated derivative of nitrazepam and therefore a chloro-nitro benzodiazepine.

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The exact mechanism  by which clonazepam exerts its anticonvulsant, sedative, and antipanic effects is unknown. However, it is believed to be related at least in part to the drug’s ability to enhance the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the central nervous system.

Indications of Clonazepam

1st choice drug for ,insomnia induce anxiety,convulsion,agitation

• Hypnotic disorder in the short-term management of insomnia, as a sedative and premedicant,
• Akinetic and myoclonic seizures. It can also be used for the treatment of panic disorders.
• Clonazepam is used as an anticonvulsant in the treatment of the Lennox-Gastaut syndrome , akinetic and myoclonic seizures. It can also be used for the treatment of panic disorders.
• Akinetic seizures
• Burning mouth syndrome
• Gilles de la tourette’s syndrome
• Lennox-gastaut syndrome (LGS)
• Mixed manic depressive episode
• Panic disorders
• Rapid eye movement sleep disorder
• Restless legs syndrome 
• Tardive dyskinesia
• Tremor?, essential
• Acute? manic episode
• Myoclonic seizures
• Refractory absence Seizures
• The treatment of acute? and chronic? akathisia induced by neuroleptics, also called antipsychotics.
• Spasticity related to amyotrophic lateral sclerosis?.
• Alcohol withdrawal syndrome
• Hyperekplexia
• Many forms of parasomnia and other sleep disorders are treated with clonazepam.

Therapeutic Indications of Clonazepam

• Clonazepam is useful alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures. In patients with absence seizures (petit mal) who have failed to respond to succinimides, Klonopin may be useful.
• Clonazepam is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV.
• Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks.
• Clonazepam also has been used in patients who experience akathisia while receiving antipsychotic drugs (e.g., for management of schizophrenia) and for the treatment of acute? catatonic reactions, whether associated with schizophrenia or other conditions.
• The efficacy of clonazepam as a hypnotic has not been fully evaluated.
• Clonazepam is a high potency benzodiazepine labeled for use as an anticonvulsant. Increasingly, clonazepam has been used in the treatment of a variety of psychiatric disorders.
• The drugs potential clinical applications, including (1) use as an adjunct to neuroleptics for treating psychosis, (2) management of specific psychotropic side effects, (3) alternative treatment for certain pain? syndromes, and (4) a primary treatment for severe agitation, atypical psychosis, and anxiety disorders
• This is a report on the efficacy of clonazepam in the treatment of acute? mania. The advantages of clonazepam over standard neuroleptics are its rapidity of action, its lack of toxicity, and, particularly important, the fact that it does not cause tardive dyskinesia, a potentially disabling neurological side effect? of neuroleptic treatment.
• Benzodiazepines, such as clonazepam, are sometimes used for the treatment of mania or acute? psychosis-induced aggression. In this context, benzodiazepines are given either alone, or in combination with other first-line drugs such as lithium, haloperidol or risperidone.
• The effectiveness of taking benzodiazepines along with antipsychotic drugs is unknown, and more research is needed to determine if benzodiazepines are more effective than antipsychotic drugs when urgent sedation is required.

Contra-Indications of Clonazepam

• Porphyria
• Having thoughts of suicide
• Alcohol intoxication
• Drug abuse
• Wide-angle glaucoma
• Closed-angle glaucoma
• Decreased lung function
• Chronic? lung disease
• Liver problems
• Severe liver disease
• Temporarily stops breathing while wleeping
• Abnormal liver function tests
• Susceptible to breathing fluid into lungs
• Pregnancy
• Kidney disease with likely reduction in kidney function
• Allergies to Benzodiazepines

Dosage? of Clonazepam

Strengths :  0.5 mg, 1 mg, and 2 mg.

Adult dosage? 

• Typical starting dose: 0.25 mg taken twice per day
• Dose increases – Your doctor may increase your dose to 0.5 mg taken two times per day after 3 days.
• Maximum dose – 4 mg per day.
• Dose reduction – Your doctor should decrease your dose slowly when stopping treatment with this drug. They should decrease your dose by no more than 0.125 mg every 3 days. For example, if you were taking 2 mg two times per day, your doctor would decrease your dose to 1.875 mg taken two times per day.
• A typical adult dose to treat seizures may start at 1.5 mg a day, divided into three doses. Your doctor may gradually increase your dose to a maximum daily dose of 20 mg.

Seizure? Prophylaxis

• 1.5 mg orally per day divided into 3 doses; this may be increased in increments of 0.5 mg to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase.
• Maximum dose: 20 mg/day

Panic Disorder

• Initial dose – 0.25 mg orally 2 times per day
• Maintenance dose – 1 mg orally per day
• Maximum dose – 4 mg/day

Seizure? Prophylaxis

• Up to 10 years of age OR 30 kg body weight: 0.01 mg/kg/day to 0.05 mg/kg/day orally administered in 2 or 3 divided doses
• Maintenance dose – 0.1 to 0.2 mg/kg/day
• 10 years or older OR 30 kg and over – 1.5 mg orally per day divided into 3 doses; this may be increased in increments of 0.5 mg to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase.
• Maximum dose – 20 mg/day

Side Effects of Clonazepam

The most common