Ativan (lorazepam) injection is a medication approved by the U.S. Food and Drug Administration for the treatment of status epilepticus and anxiety.
It is also available as a pill and liquid solution (Ativan Intensol). These formulations are, however, not approved for the treatment of seizures.
Ativan injection is used as a rescue medication to stop status epilepticus in Batten disease patients. It must be administered by a healthcare professional, and is not intended to replace anticonvulsant medications that have to be taken daily.
How Ativan works
Ativan binds to a type of GABA receptor, called GABAA, and activates it in a similar way to GABA. GABA is a signaling molecule that inhibits nerve cell signaling. Through this mechanism, Ativan is thought to reduce the uncontrolled firing of neurons that causes seizures.
Ativan in clinical trials
A randomized, placebo-controlled Phase 3 clinical trial (NCT00004297) assessed the effect of Ativan in 205 epilepsy patients with a history of status epilepticus. During the trial, patients received either 5 mg of intravenous diazepam, 2 mg of Ativan, or a placebo upon the onset of status epilepticus. If the seizure continued for four minutes after the injection, an identical second injection was administered.
The primary outcome measure was the termination of status epilepticus. This was the case in 59.1% of patients who received Ativan, 42.6% who received diazepam, and 21.1% who received placebo. Ativan and diazepam were both statistically more efficient than placebo. The difference between Ativan and diazepam was, however, not statistically significant.
Another randomized, open-label Phase 3 clinical trial (NCT00343096) compared the effectiveness of three different routes of Ativan administration: buccal (by injection into the lower gum or cheek), intranasal (through the nose), and intravenous (injected into the bloodstream). When a continuous seizure occurred, 100 ug/kg body weight of Ativan was administered buccally in 252 patients, intranasally in 245 patients, and intravenously in 264 patients.
With intravenous Ativan, seizures stopped within 10 minutes of administration in 81% of patients, while with the intranasal administration, they stopped in 57% of patients, and with the buccal administration, in 46% of patients. The study was terminated early because the buccal route was not effective enough in stopping seizures.
An ongoing Phase 3 clinical trial (NCT01870024) aims to compare the effectiveness of intravenous Ativan, Klonopin, and Klonopin in combination with fosphenytoin in stopping status epilepticus. The trial is currently recruiting patients at the Hôpital Lariboisière in Paris.
Additional information
Ativan injection is associated with an increased risk of respiratory depression. Therefore, respiration needs to be carefully monitored following Ativan injection.
Common side effects include headaches, low blood pressure, somnolence, and respiratory failure.
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