Hero or Antagonist: A Case Series on the Tolerability of Memantine as Salvage Therapy for Catatonia From NMDA-Receptor Encephalitis

Abstract: From October 2021-January 2022, the Consultation-Liaison Psychiatry team at a large academic hospital cared for two previously healthy patients who were diagnosed with catatonia due to NMDA-Receptor Encephalitis (NMDARE). The first, a 25-year-old man, presented with severe physical aggression that developed into catatonia. Workup with MRI brain, lumbar puncture (LP), and EEG was negative, but a testicular ultrasound revealed a seminoma as the underlying cause for his NMDARE. This was confirmed on CSF autoimmune panel. He was treated with IV corticosteroids, IVIG, and IV lorazepam 24 mg total daily dose without response. He then received an orchiectomy and IV rituximab. He was discharged home on memantine 10 mg twice daily, valproic acid, aripiprazole, and lorazepam.

The second, a 19-year-old woman presented with behavioral changes following seizures. She was diagnosed with catatonia due to NMDARE after findings of oligoclonal bands on LP and abnormal video EEG. This was confirmed on CSF autoimmune panel. An underlying cause was never identified. She received IV corticosteroids, IVIG, cyclophosphamide, IV lorazepam 12 mg total daily dose, valproic acid, amantadine, and nine ECT sessions without response. She tolerated memantine 10 mg twice daily and two infusions of rituximab with mild improvements in episodes of restlessness.

This case series illustrates several key points regarding the diagnosis and management of catatonia due to NMDARE. First, catatonia has a medical etiology in up to 46% of cases (1), and this rate increases with age and level of care (2). Second, about 20-30% of cases do not respond to treatment with benzodiazepines and alternative treatments are available (3). There is growing case series level evidence of the use of NMDA antagonists, such as memantine, in the treatment of benzodiazepine-resistant catatonia through its direct glutamate antagonism and indirect GABA and dopamine effects. These findings are based on the hypothesis that NMDA hyper-excitability in striato-cortical and corticocortical pathways and loss of GABA-A and dopamine may represent the pathophysiology of benzodiazepine-resistant catatonia (4). However, given its antagonistic activity at the NMDA receptor, memantine should theoretically worsen NMDARE and thus the associated catatonia. In turn, many clinicians are hesitant to prescribe memantine for such cases, with scant evidence to refute this. This is a unique case series that demonstrates memantine’s utility and safety profile in cases of NMDARE-induced catatonia.


References:

1.Stern, TA (2018). Massachusetts General Hospital Handbook of General Hospital Psychiatry. Elsevier Inc.

2. Oldham MA. The Probability That Catatonia in the Hospital has a Medical Cause and the Relative Proportions of Its Causes: A Systematic Review [published correction appears in Psychosomatics. 2018 Nov;59(6):626]. Psychosomatics. 2018;59(4):333-340.

3.Beach SR, et al. Alternative treatment strategies for catatonia: A systematic review. Gen Hosp Psychiatry. 2017;48:1-19.

4.Hervey WM, et al. Treatment of catatonia with amantadine. Clin Neuropharmacol. 2012;35(2):86-87.