Effectiveness of amantadine and memantine in catatonia: A retrospective cohort study

Background: Catatonia is a neuropsychiatric syndrome involving motor, behavioral, cognitive, and affective dysfunction that is associated with substantial morbidity and mortality. While benzodiazepines and electroconvulsive therapy (ECT) are first-line treatments for catatonia, alternative pharmacologic options are often used when response is inadequate or ECT is unavailable. N-methyl-D-aspartate receptor antagonists, particularly amantadine and memantine, have been used as second-line agents, though evidence remains limited to case reports and small series. Objective: To evaluate the effectiveness of amantadine and memantine in hospitalized adults with catatonia by assessing changes in symptom severity measured by the Bush-Francis Catatonia Rating Scale (BFCRS). We hypothesized that these agents, when used alongside standard treatments, would generate symptom improvement. Methods: A retrospective study of adults hospitalized at Massachusetts General Hospital from 2016 to 2024 was conducted. Patients hospitalized with a diagnosis of catatonia who were treated with memantine or amantadine were identified from clinical records. Catatonia severity was measured using clinically documented BFCRS scores. Pre-post BFCRS changes were analyzed using Wilcoxon signed-rank tests, with planned sensitivity analyses. Results: Fifty-seven patients received amantadine or memantine for catatonia, mostly as adjunctive treatment. One week (±2 days) after initiation, BFCRS total scores decreased by a mean of 4.9 points ( p < 0.001, r = 0.61). Results remained significant when excluding patients who received ECT during the first week of amantadine or memantine treatment ( n = 48; mean change 5.0, p < 0.001) and those with ⩾50% lorazepam-equivalent dose increases ( n = 39; mean change 4.6, p < 0.001). Conclusion: This represents the largest cohort treated with amantadine or memantine for catatonia. Findings suggest significant symptom reduction, supporting their potential role as an adjunctive option. Prospective studies are needed to clarify predictors of response and comparative effectiveness.