Amantadine-Responsive, Benzodiazepine-Resistant Catatonia in an Adolescent With Autism Spectrum Disorder

BACKGROUND: Catatonia is a severe neuropsychiatric syndrome increasingly recognized in autism spectrum disorder (ASD), where symptom overlap can delay diagnosis. In pediatric populations, it is associated with significant morbidity and requires prompt intervention. Benzodiazepines and electroconvulsive therapy (ECT) are first-line treatments; however, access to ECT may be limited due to legal or institutional constraints. Alternative pharmacological strategies, including N-methyl-D-aspartate (NMDA) receptor antagonists such as amantadine, have been proposed, although evidence remains limited. CASE PRESENTATION: We report a 15-year-old male with ASD who developed progressive catatonia over 1 year, with psychomotor slowing, speech latency, staring, and functional decline requiring hospitalization. Symptoms emerged after using over-the-counter supplements and partially improved after discontinuation. Medical and neurological workup was unremarkable. A lorazepam challenge produced partial improvement, but high-dose benzodiazepines were insufficient. Due to lack of access to ECT, amantadine was initiated and titrated to 200 mg twice daily. Within days, the patient showed marked improvement, including increased speech output, improved psychomotor activity, and enhanced social engagement. Improvement was supported by clinical observations and caregiver reports. DISCUSSION: Catatonia involves dysfunction in dopaminergic (DA), GABAergic, and glutamatergic systems within cortico-striato-thalamo-cortical circuits. In ASD, similar abnormalities in excitatory-inhibitory balance and connectivity have been reported, which may partly explain the overlap in presentation and the potential vulnerability to catatonia. Amantadine may help restore this imbalance through NMDA receptor antagonism and DA modulation. CONCLUSION: Amantadine may be a viable adjunctive treatment for benzodiazepine-insufficient catatonia in adolescents with ASD when lorazepam is insufficient or poorly tolerated and ECT is unavailable. Further research is needed.