Levetiracetam

Focal epilepsy Levetiracetam is effective as single-drug treatment for newly diagnosed focal epilepsy in adults. It reduces focal seizures by 50% or more as an add-on medication. Generalized epilepsy Levetiracetam is effective for the treatment of generalized tonic-clonic epilepsy. Levetiracetam is sometimes used as off-label treatment for status epilepticus. Prevention of seizures Based on low-quality evidence, levetiracetam is about as effective as phenytoin for the prevention of early seizures after traumatic brain injury. It may be effective for prevention of seizures associated with subarachnoid hemorrhages. Other Levetiracetam has not been found to be useful for treatment of neuropathic pain, nor for treatment of essential tremors. Levetiracetam has not been found to be useful for treating developmental disorders within the autism spectrum, with studies finding it effective only in the setting of partial, myoclonic, or tonic-clonic seizures associated with autism spectrum disorder. Pregnancy Levetiracetam is considered to be one of the safest anti-seizure medications during pregnancy. Studies show rates of birth defects that are similar to patients who are not taking an anti-seizure medication. Studies were conducted to look for increased adverse effects in the elderly population as compared to younger patients. One such study published in Epilepsy Research showed no significant increase in incidence of adverse symptoms experienced by young or elderly patients with disorders of the central nervous system. Levetiracetam is the most commonly prescribed initial antiepileptic drug in children aged 1–36 months. One study found 66% of participants to be seizure-free after an average of 12 months on levetiracetam, a relatively high percentage compared to other antiepileptics. == Adverse effects ==

The most common adverse effects of levetiracetam treatment include effects on the central nervous system such as somnolence, decreased energy, headache, dizziness, mood swings and coordination difficulties. These adverse effects are most pronounced in the first month of therapy. About 4% of patients dropped out of pre-approval clinical trials due to these side effects. Although rare, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which present as a painful, spreading rash with redness, blistering, and/or peeling skin, have been reported in patients treated with levetiracetam. The incidence of SJS following exposure to anti-epileptics such as levetiracetam is about 1 in 3,000. Levetiracetam should not be used in people who have previously shown hypersensitivity to levetiracetam or any of the inactive ingredients in the tablet or oral solution. Such hypersensitivity reactions include, but are not limited to, unexplained rash with redness or blistered skin, difficulty breathing, and tightness in the chest or airways. Suicide Levetiracetam, along with other anti-epileptic drugs, can increase the risk of suicidal behavior or thoughts. Patients taking levetiracetam should be monitored closely for signs of worsening depression, suicidal thoughts or tendencies, or any altered emotional or behavioral states. Kidney and liver Kidney impairment decreases the rate of elimination of levetiracetam from the body. Individuals with reduced kidney function may require dose adjustments, guided by monitoring of kidney function. The pharmacokinetic profile of levetiracetam is not influenced by phenytoin, phenobarbital, primidone, carbamazepine, valproic acid, lamotrigine, gabapentin, digoxin, ethinylestradiol, or warfarin. == Mechanism of action ==

The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. Levetiracetam does not exhibit pharmacologic actions similar to that of classical anticonvulsants. It does not inhibit voltage-dependent Na+ channels, does not affect GABAergic transmission, and does not bind to GABAergic or glutamatergic receptors. However, the drug binds to SV2A, a synaptic vesicle glycoprotein, and inhibits presynaptic calcium channels, reducing neurotransmitter release and acting as a neuromodulator. This is believed to impede impulse conduction across synapses. As of 2024, this is widely accepted to be its mechanism of action. However, the molecular basis of this action remains unknown. == Pharmacokinetics ==

The FDA provided a detailed review of the pharmacology and biopharmaceutics of levetiracetam in 2013. Analogues Brivaracetam, a chemical analogue to levetiracetam, is a racetam derivative with similar properties. However, it has a 15-30 times higher affinity for the SV2A protein and is less likely to produce psychiatric adverse effects compared to levetiracetam. It is also unique from levetiracetam because it undergoes hepatic metabolism. ==Society and culture==

Levetiracetam is available as regular and extended release oral formulations and as intravenous formulations. The immediate release tablet has been available as a generic in the United States since 2008, and in the UK since 2011. The patent for the extended release tablet will expire in 2028. The branded version Keppra is manufactured by UCB Pharmaceuticals S.A. Some have said that the drug has been improved by 3D printing, as the formula used now has improved disintegration properties. Legal status Australia Levetiracetam is a Schedule 4 substance in Australia under the Poisons Standard (February 2020). A Schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription." Travelers who plan to bring more than a month's worth must apply for an import certificate, known as a . ==Research==

Levetiracetam has been studied in the past for treating symptoms of neurobiological conditions such as Tourette syndrome, and anxiety disorder. However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood. Some preliminary studies have suggested that levetiracetam may improve cognition in Alzheimer's disease patients with epileptiform activity. However, the results of larger randomized studies are required before it can be recommended for clinical use for this indication. Additionally, levetiracetam has been experimentally shown to reduce levodopa-induced dyskinesia, a type of movement disorder, or dyskinesia associated with the use of levodopa, a medication used to treat Parkinson's disease. Many antiepileptic drugs cause changes in basic EEG activity. These include, in particular, carbamazepine, benzodiazepines, and phenobarbital. However, the effect of levetiracetam on basic EEG activity is minimal; no measurable increase in drug-induced beta activity was observed. At the same time, a significant reduction in seizure-like EEG abnormalities was observed. Of the ten medications evaluated in a 2023 systematic review of the literature, levetiracetam was found to be the only medication with sufficient evidence showing that it may cause seizure freedom in some infants. Further, adverse effects from levetiracetam were rarely severe enough for the medication to be discontinued in this age group. Because available research included only two published studies reporting seizure freedom rates, however, the strength of the evidence was judged to be low. == History ==

Levetiracetam was discovered during evaluation of various analogs of piracetam. In 1964, piracetam was first synthesized with the aim of developing medications to help with sleep. However, piracetam was not found to help with sleep but rather appeared to have some cognitive boosting effects. Later on etiracetam, an ethyl analog of piracetam, was synthesized. Subsequently, levetiracetam, an S-enantiomer, of etiracetam was identified. Levetiracetam did not show any positive effects on cognition in humans but was tested in epilepsy models since piracetam had some beneficial effects in treatment of myoclonus and photoparoxysmal responses. Further testing showed that levetiracetam had potent anti-seizure effects. The anti-seizure effect of levetiracetam was first identified during screening of various compounds against epileptiform activity in sound-sensitive mice. Unlikely previously known anti-seizure medications, levetiracetam showed no effect in the maximal electroshock or pentylenetrazol seizure tests. Levetiracetam was distinct from previously known anti-seizure medications as it seemed to show efficacy in chronic epilepsy models as opposed to acute seizure models. == References ==