Klonopin (Clonazepam)

Klonopin (clonazepam) is an anticonvulsant medication that is used to control various types of seizures and panic attacks. It is marketed by Genentech.

The medicine may be of benefit in treating seizures in patients with Dravet syndrome.

How Klonopin works

Klonopin works as a GABA agonist, or a molecule that acts in the same way as GABA. GABA is a neurotransmitter, a signaling molecule in the brain that inhibits the activity of brain cells. It performs its inhibitory action by binding to GABA receptors. Klonopin binds to one of these receptors, GABAA, and block nerve cell activity in a similar way to GABA.

In Dravet syndrome, 70 percent to 85 percent of patients are known to carry a mutation in the SCN1A gene, which provides instructions to build the so-called NaV1.1 subunit of sodium channels. Nerve cells communicate with each other via electric signals, and sodium channels are essential for the transmission of these signals. The SCN1A mutations in Dravet syndrome are thought to mainly affect GABAergic neurons, or neurons that release GABA. They lead to aberrant nerve cell signaling, which results in seizures.

Klonopin is thought to help Dravet syndrome patients by compensating for the unbalanced activity of GABAergic neurons.

Klonopin in clinical trials for Dravet syndrome

Klonopin has not been tested in randomized clinical trials specifically for Dravet syndrome patients. However, a preclinical study in mice and a retrospective study suggest  it might be of benefit to Dravet syndrome patients.

In the preclinical study, published in 2013, a mouse model of Dravet syndrome with a mutation in the SCN1A gene was treated with Klonopin, and the treatment protected the mice from thermally induced clonic seizures.

In the retrospective study, published in 2016, the medical records of 215 Dravet syndrome patients were analyzed; 128 patients had a known SCN1A mutation, and 87  had no mutations in the SCN1A gene. In the patient group with SCN1A mutations, 46  used Klonopin; in the group without SCN1A mutations, 29 patients used Klonopin.

A decrease in seizure frequency by more than 50 percent upon taking Klonopin was 43.48 percent among patients with an SCN1A mutation, and 37.93 percent of patients without an SCN1A mutation. The difference in efficacy between the two groups was statistically not significant.

Additional information

Klonopin should not be used in patients with severe liver disease or narrow-angle glaucoma, a condition characterized by a blockage of the drainage canals in the eye, leading to an increased internal eye pressure.

Klonopin use is associated with an increased risk of suicidal thoughts and behavior. Patients using it  should be monitored for depression, suicidal thoughts, and changes in mood or behavior.

Common side effects of Klonopin include drowsiness, ataxia, shallow breathing, pounding heartbeat, and involuntary eye movements.


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