Lorazepam: a controlled trial in patients with intractable partial complex seizures.

Area of Science:

• Neurology
• Clinical Pharmacology

Background:

• Partial complex seizures are often refractory to standard anticonvulsant therapies.
• Identifying effective adjunctive treatments for drug-resistant epilepsy is crucial.

Purpose of the Study:

• To evaluate the efficacy and safety of lorazepam as an add-on therapy for patients with frequent partial complex seizures.
• To determine the therapeutic window for lorazepam in this patient population.

Main Methods:

• A double-blind, placebo-controlled, crossover trial was conducted in eight patients with refractory partial complex seizures.
• Patients received either placebo or escalating doses of lorazepam (1 mg BID), with concomitant antiepileptic drugs maintained.
• Seizure frequency was compared during the final two weeks of each treatment period.

Main Results:

• Seven out of eight patients experienced a reduction in seizure frequency with lorazepam treatment.
• The eighth patient showed a decrease in seizure duration.
• Seizure improvement was observed at lorazepam concentrations of 20-30 ng/ml, with side effects emerging above 33 ng/ml.

Conclusions:

• Lorazepam demonstrates utility as an adjunctive treatment for refractory partial complex seizures.
• Therapeutic drug monitoring is essential due to a narrow therapeutic window.
• Abrupt discontinuation of lorazepam may lead to an exacerbation of seizure frequency.