A clinical safety evaluation comparing brivaracetam and levetiracetam for epilepsy

A brain-related neurological disorder called epilepsy increases a person's risk of experiencing frequent, spontaneous seizures. It is one of the most widespread nervous system disorders, affecting individuals of all ages, races, and ethnicities. It affects approximately 50 million people around the world.

Abnormal electrical impulses in a cluster of brain cells cause seizure episodes. From the smallest attention-deficit or muscular twitches to severe and protracted convulsions, seizures can take many different forms. The frequency of seizures can also differ, ranging from fewer than one per year to multiple per day.

Seizures can result from anything that disrupts the regular connections between brain cells, such as head trauma, low blood sugar, alcohol or drug withdrawal, or a high fever.

Anyone can experience one or more seizures in these conditions. On the other hand, a person is diagnosed with epilepsy if they experience two or more recurrent, spontaneous seizures.

Epilepsy may result from a variety of factors, such as an imbalance in the chemicals called neurotransmitters that communicate nerves, tumors, strokes, and damage to the brain from disease or trauma, alone or in combination. The majority of the time, epilepsy may have no known etiology.

Seizures can take many different forms like ;

• absence-related seizures.

• Seizures with atonic behavior

• Abnormal Absence Convulsions.

• seizures with clonic movements.

• infantile spasms or epilepsy.

• febrile convulsions.

• Focal Bilateral Tonic Clonic Seizures

• Simple Partial Seizures

Management of Epilepsy:

The core component of pharmacological management of epilepsy is the use of anti-epileptic medications. Patients are frequently treated with a variety of AEDs, the choice of which is determined by the patient's characteristics like age, type and frequency of seizures, concomitant diseases, and medications such as safety profile, pharmacological interactions.

Levetiracetam (LEV) and Brivaracetam(BRV) are two of the drugs used in the treatment of epilepsy. There are pills, oral solution, and injection forms available for both medications. Brivaracetam is slightly newer drug than levetiracetam. Discovered as an analog of the related racetam drug LEV, BRV is an anti-epileptic medication belonging to the racetam group.

Brivaracetam and Levetiracetam work by targeting the brain's synaptic vesicle protein 2A (SV2A). Compared to levetiracetam, the more recent medication brivaracetam is said to be more selective and to have a higher affinity for this receptor. Both medications have FDA approval for use in various formulations.

Of all the medications on the market, levetiracetam is a highly effective treatment for seizures and is frequently used as the first choice. Partial-onset seizures are treated with levetiracetam and brivaracetam as monotherapies.

Pharmacokinetic properties

Levetiracetam has, arguably, shown a better efficacy/tolerability balance than any other antiepileptic medication due to its broad spectrum of anticonvulsant activity, relatively high and quick anti-seizure effects, favorable pharmacokinetic profile, low risk of drug-drug interactions, and moderate potential for side effects.

Being extremely lipophilic, BRV can enter the brain significantly more quickly than LEV. It engages with SV2A in a matter of minutes after passively diffusing across the blood–brain barrier without the need for transporters.

Approximately 20% of plasma proteins have weak bindings of BRV, having a distribution volume of 0.6 L/kg. Brivaracetam has an average elimination half-life of 7-8 hours, which is dose-independent.

Two days of consecutive doses are usually required to reach the steady-state concentration. The liver breaks down BRV into three inactive metabolites by substantial metabolism. Brivaracetam is a selective analogue of levetiracetam that is a derivative of (4R)-propyl (SV2A).

Recently, brivaracetam has become available in a number of countries worldwide as an additional antiepileptic medication for the treatment of focal and secondary generalized seizures.

Side effects of BRV & LEV

Brivaracetam frequently causes sleepiness or drowsiness, lightheadedness, exhaustion, and nausea or vomiting as adverse effects.

The administration of levetiracetam, however, has been associated with an increased risk of psychiatric adverse effects, such as anxiety, depression, aggression, and emotional lability, asthenia, infection, irritability, and drowsiness. according to several clinical investigations.

Mood swings, heightened aggression, or irritability are the most common side effects that lead patients to stop receiving levetiracetam.

Numerous clinical investigations have revealed that BRV may be able to reduce psychobehavioral side effects, including as aggressiveness and depressed symptoms, that have been linked to previous levetiracetam treatment in individuals with epilepsy who also have mental comorbidities.

Additionally, results from one of the trials revealed that switching to brivaracetam could help improve behavioral side effects in epileptic individuals who had mental health issues related to previous levetiracetam medication.

Mechanism of action of both the drugs

At the glutamatergic synapse, levetiracetam blocks excitatory neurotransmission by blocking N-type calcium channels on the presynaptic neuron. By doing this, the cell is unable to absorb calcium, which stops the exocytosis of glutamate-containing intracellular vesicles.

Brivaracetam blocks sodium channels in a voltage-dependent manner, and it has a ligand affinity for the SV2A that is ten times larger than that of Levetiracetam. The efficacy of anticonvulsants and SV2A binding affinity appear to be correlated.

Research conducted on a smaller patient sample size also revealed that an overnight changeover from levetiracetam to brivaracetam with dosing ratios of 15:1 and 10:1 is a safe and well-tolerated treatment option.

According to the results of one study comparing the favorable adverse effect profile of brivaracetam and levetiracetam in a preclinical model, In comparison to levetiracetam, the brivaracetam is known to have higher lipophilicity and faster brain penetration.

Furthermore, due to brivaracetam’s stronger potency and greater affinity for the SV2A target, the doses required to have an anticonvulsant effect in vivo and in vitro are substantially lower—nearly ten times lower.

Developing treatment strategies One could opt to use 1,000 mg levetiracetam for 50 mg of brivaracetam, 2,000 mg levetiracetam for 100 mg of brivaracetam, and 3,000 mg levetiracetam for 200 mg of brivaracetam . Because of the preceding ratios, these two medications can be quickly switched out in an emergency.

From a variety of research that it can be said there are no appreciable variations between levetiracetam and brivaracetam in terms of the treatment outcomes that are measured.

LEV appears to be somewhat more efficient and less prone to induce vertigo. It will take careful observation of the results of "real life" treatment with BRV to show whether or not this medication is useful in the usual treatment of epileptic patients.