Review Finds Ativan Best for Treating Severe Epilepsy

Armen Hareyan's picture

Treatment of Epileptic Seizures

The drug Ativan is better than Valium or Dilantin for controlling severe epileptic seizures, according to a new review of studies.

Ativan, or lorazepam, and Valium, or diazepam, are both benzodiazepines, the currently preferred class of drugs for treating severe epileptic seizures. Dilantin, or phenytoin, is an anticonvulsant long used for the treatment of epileptic seizures.

The review also finds that a 30-mg diazepam gel is better than the 20-mg gel for treating the milder epileptic seizures that lead up to the medical emergency of full-blown, continuing or repetitive seizures.

Researchers Kameshwar Prasad of All India Institute of Medical Science and colleagues analyzed 11 randomized studies involving 2,017 patients.

Patients in the studies experienced either or both status epilepticus (SE), a condition in which a person experiences more than 30 minutes of continuous seizure activity or two or more sequential seizures without regaining full consciousness, and premonitory seizures, shorter events that generally occur with increasing frequency and severity before an SE emergency.

The studies involved the use of the anesthetic Versed, or midazolam, and phenobarbitone, a barbiturate, as well as lorazepam, diazepam, and phenytoin.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

A Cochrane review of anticonvulsant therapy for SE was published in 2002. It focused on children and did not include several studies involving adults. The new review closes this gap, and studies involving both convulsive as well as non-convulsive SE are included.


Gregory L. Barkley, the chair of the Professional Advisory Board of the Epilepsy Foundation of American and a neurologist at the Henry Ford Hospital in Detroit, said the review is not surprising in its findings: "Lorazepam and diazepam do offer the best means for stopping SE abruptly, but it should be noted that phenytoin is important as a follow-up drug."

Barkley said he hopes the review will change treatment behaviors. Diazepam often is the only anticonvulsant available outside hospital settings because such drugs are not frequently used, and many require refrigeration, unlike diazepam.

In addition, Barkley noted that midazolam, which was assessed in three of the studies, "is an emerging treatment under active investigation." However, he said that "not enough data has yet been generated about the drug for an evidence-based recommendation for its use."

A number of conditions may precipitate SE, including toxic or metabolic causes and anything that might cause cortical structural damage like stroke, hypoxic injury, tumors, hemorrhages, trauma, toxicologic sources (such as cocaine or alcohol withdrawal), electrolyte abnormalities and infections (such as meningitis and encephalitis).

Among children who experience SE, 8 percent die. Among adults, the death rate is 30 percent. Another 5 percent to 10 percent are permanently left in a vegetative state or with cognitive difficulties.

Other outcomes include disabilities severe enough to require dependence on others for activities of daily living, ranging from bathing to dressing to eating and walking; the need for ventilatory support; and incomplete recovery.

Between 50,000 and 200,000 cases of SE occur each year in the United States.

The review identifies several areas requiring attention in future SE research, such as agreed-on definitions for different types of seizures. It also says "agreement on the definition of outcomes and method of data presentation [are] also desirable."

Finally, the review notes a practical difficulty in conducting randomized controlled trials in SE. Obtaining the consent of participants is impossible when they are unconscious or not in a state where they can provide consent. Gaining such consent from next of kin is an option highlighted in the review.


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