Revisiting lorazepam challenge test: Clinical response with dose variations and utility for catatonia in a psychiatric emergency setting

Abstract

Objective: Catatonia can be life-threatening unless timely identified and treated. Lorazepam's ubiquitous response has led to its universal acceptance as being the first-line management of catatonia and alludes to catatonia's neurobiological underpinnings. Lorazepam challenge test (LCT) is widely used to either confirm a catatonia diagnosis or determine lorazepam sensitivity. It has a proposed schedule for administering lorazepam. However, efficacy of recommended LCT doses lack systematic evidence, resulting in variable LCT doses used in clinical and research settings contributing to findings that are challenging to generalize or assist with developing standardized lorazepam treatment protocols for catatonia. Given the same, this study aimed to objectively compare the response between two groups receiving different LCT doses and factors influencing the same.

Methods: The 6-month study in a psychiatric emergency setting at a tertiary neuropsychiatric center in India evaluated 57 catatonia patients, before and after administration of single 2 mg (n = 37; LCT-2) or 4 mg (n = 20; LCT-4) lorazepam dose, applying Bush Francis Catatonia Rating Scale (BFCRS), Mini International Neuropsychiatric Interview (MINI 5.0) and obtaining sociodemographic, clinical data.

Results: No between-group differences (LCT-2 vs LCT-4) for sociodemographic, clinical profiles or BFCRS severity score changes to lorazepam on Mann-Whitney U test were noted. Applying Wilcoxon signed rank test comparing individual sign severity demonstrated response variability, with significant response noted to both doses (stupor, mutism, staring, posturing, withdrawal, ambitendency, automatic obedience) and others selectively to 2 mg (echolalia, rigidity, negativism, mitgehen). Notably, sign resolution (present/absent) only to 2 mg was significant for stupor, mutism, staring, posturing, echolalia, rigidity, negativism and mitgehen.

Conclusion: This study suggests 2 mg lorazepam may be an optimal LCT dose, given significant response to most catatonic signs thereby ensuring accurate detection and preventing misinterpretation of response. It offers future studies direction for standardizing lorazepam dosing schedules for catatonia management and exploring neurobiological underpinnings for individual catatonic signs that may be potentially different, given these findings.

Keywords: Bush Francis Catatonia Rating Scale; Catatonia; catatonic signs; lorazepam challenge test; neurobiology.