Comparative effectiveness of lorazepam versus diazepam for acute catatonia: A retrospective analysis

Catatonia is a neuropsychiatric disorder that can respond rapidly to treatment with benzodiazepines. Historically, lorazepam is the most used agent for "the lorazepam challenge test" (LCT), but comparative evidence for alternative benzodiazepines remains limited. A temporary intravenous (IV) lorazepam shortage within our health system created a natural experiment by restricting access to lorazepam. We use this natural experiment to compare a single dose of IV diazepam vs. IV lorazepam for the acute treatment of catatonia in a LCT.

Retrospective comparative effectiveness study of adults with clinically diagnosed catatonia treated during a period of IV lorazepam shortage (July-November 2025) who received IV diazepam and had Bush-Francis Catatonia Rating Scale (BFCRS) assessments before and after benzodiazepine administration. These patients were compared with an equal number of patients treated with IV lorazepam in adjacent non-shortage periods. The primary outcome was change in BFCRS following a single dose of benzodiazepine. Between-group differences in change scores were analyzed using Welch's t-test, with Mann-Whitney U test sensitivity analysis.

Twenty patients met inclusion criteria (10 diazepam; 10 lorazepam). Baseline BFCRS severity was similar between groups (overall mean 15.6 ± 6.2). Across the full cohort, benzodiazepine administration produced a large within-subject improvement in catatonia severity (mean BFCRS change -5.8 ± 5.0; p < 0.001; Hedges' g = 1.12). Mean BFCRS change was -6.8 ± 6.6 in the diazepam group and - 4.9 ± 2.6 in the lorazepam group. The between-group difference in improvement (diazepam - lorazepam) was -1.90 BFCRS points (95% CI -6.83 to +3.03), corresponding to a negligible effect size and was not statistically significant (p = 0.42). Any improvement occurred in 9 diazepam-treated patients and all lorazepam-treated patients.

In this quasi-experimental cohort, a single dose of IV diazepam produced short-term reductions in catatonia severity comparable in magnitude to a single dose of IV lorazepam in the LCT. Although underpowered to establish equivalence, these findings provide preliminary empirical support for IV diazepam as a viable acute treatment option when lorazepam is unavailable.