Response of early status epilepticus to benzodiazepines in chronic benzodiazepine users: A case-control study

Benzodiazepines (BZDs) are the recommended first-line treatment in early status epilepticus (SE). At least 30% of episodes are resistant, leading to established SE. Chronic BZD use may induce pharmacological tolerance. We hypothesized that chronic exposure to BZDs may reduce their efficacy as first-line treatment in early SE.

This retrospective case-control study included SE episodes from 2010 to 2023 at a tertiary center in Brussels. Postanoxic and Alcohol- or BZD withdrawal-related SE episodes were excluded, as well as those in which BZDs were not used as first-line treatment. Chronic BZD use was defined as a daily use for at least 6 months. Chronic BZD users (cases) were matched 1:1 with nonusers (controls) for age, sex, etiology, and semiology. Univariable and multivariable comparisons were performed. The primary outcome was evolution of early SE to established SE, defined as the use of second-line treatment.

Ninety-eight cases and 98 controls were included and matched. Chronic use of BZDs was associated with more frequent need for second-line treatment or evolution to established SE (85% vs. 64%, p = .022). Established SE (n = 146) was also associated with longer in-hospital stay (15 vs. 5 days, p < .001) and more complications (Complications Burden Index: 1 vs. 2.5, p < .001). After adjusting for both timing and dose of first-line treatment, multivariable analysis confirmed chronic BZD use as an independent risk factor for established SE (odds ratio = 3.34, 95% confidence interval = 1.66-7.03, p = .001). Among chronic users, no association was observed between modalities of BZD chronic use (dose, half-life time, duration) and the establishment or refractoriness of SE episodes.

Chronic BZD use is associated with a higher rate of second-line treatment administration in SE, suggesting greater resistance to acute BZD administration. This association should be considered when managing early SE. Chronic BZD use should be considered with extreme caution in patients with epilepsy at risk of SE.