Clinical Course of Amantadine in Patients with Prolonged Consciousness Disorder in the Intensive Care Unit

Abstract

Background and Aims: This study aimed to evaluate the clinical course of amantadine treatment on consciousness recovery in patients with prolonged impairment admitted to the intensive care unit (ICU) for various reasons. Methods: This was a retrospective descriptive study. The study included patients hospitalised in the ICU within 2 years (01.01.2022-01.09.2023) and who were administered intravenous amantadine to treat the prolonged consciousness disorder. Improvement in consciousness was defined as at least a two-point increase in the Glasgow Coma Scale (GCS) score. Results: This study encompassed 21 participants, with an average age of 68.3±17.6 years. The median (Inter Quantile Range [IQR]) starting dose of amantadine was 400 mg/day (150-600), initiated 16.6±9.5 days post ICU admission. Notably, 76.2% experienced consciousness recovery within a median (IQR) time of 3.5 days (2-5.75) after amantadine initiation. A significant positive correlation between consciousness recovery and sex (r: 0.533, p:0.013) was observed, with all men and 45.4% of women achieving recovery. Chi-square analysis indicated a sex-related significant difference in consciousness recovery status (p:0.015). However, the logistic regression analysis failed to establish a meaningful model. Conclusion: Amantadine treatment shows promise in improving cognitive status in ICU patients with prolonged consciousness disorders. Further confirmatory studies with larger sample sizes, randomised designs, and standardised outcome measures are warranted to validate these findings.

Keywords

• Amantadine
• Recovery of Consciousness
• Prolonged Consciousness Disorder
• Intensive Care Unit

References

1. Abbasivash, R., Valizade Hasanloei, M. A., Kazempour, A., Mahdkhah, A., Shaaf Ghor-eishi, M. M., & Akhavan Masoumi, G. (2019). The effect of oral administration of amantadine on neurological outcome of patients with diffuse axonal injury in ICU. Journal of Experimental Neuroscience, 13, 1179069518824851. https://doi. org/10.1177/1179069518824851 google scholar
2. Akçıl, E. F., Dilmen, K. Ö., Vehid, H., & Tunalı, Y. (2018). Can amantadine ameliorate neurocognitive functions after subarachnoid haemorrhage? A preliminary study. Turkish Journal of Anaesthesiology and Reanimation, 46(2), 100–107. https://doi.org/10.5152/TJAR.2018.20280 google scholar
3. Avecillas-Chasín, J. M., & Barcia, J. A. (2014). Effect of amantadine in minimally conscious state of non-traumatic etiology. Acta Neurochirurgica, 156(7), 1375– 1377. https://doi.org/10.1007/s00701-014-2077-x google scholar
4. Barra, M. E., Izzy, S., Sarro-Schwartz, A., Hirschberg, R. E., Mazwi, N., & Edlow, B. L. (2020). Stimulant therapy in acute traumatic brain injury: Prescribing patterns and adverse event rates at 2 level 1 trauma centers. Journal of Intensive Care Medicine, 35(11), 1196–1202. https://doi.org/10.1177/0885066619841603 google scholar
5. Chan, Y. H. (2003). Biostatistics 104: Correlational analysis. Singapore Medical Journal, 44(12), 614–619. google scholar
6. Gagnon, D. J., Leclerc, A. M., Riker, R. R., Brown, C. S., May, T., Nocella, K., Cote, J., Eldridge, A., & Seder, D. B. (2020). Amantadine and modafinil as neurostimulants during post-stroke care: A systematic review. Neurocritical Care, 33(1), 283–297. https://doi.org/10.1007/s12028-020-00977-5 google scholar
7. Giacino, J. T., Whyte, J., Bagiella, E., Kalmar, K., Childs, N., Khademi, A., Eifert, B., Long, D., Katz, D. I., Cho, S., Yablon, S. A., Luther, M., Hammond, F. M., Nordenbo, A., Novak, P., Mercer, W., Maurer-Karattup, P., & Sherer, M. (2012). Placebo-controlled trial of amantadine for severe traumatic brain injury. The New England Journal of Medicine, 366(9), 819–826. https://doi.org/10.1056/NEJMoa1102609 google scholar
8. Gramish, J. A., Kopp, B. J., & Patanwala, A. E. (2017). Effect of amantadine on agitation in critically ill patients with traumatic brain injury. Clinical Neuropharmacology, 40(5), 212–216. https://doi.org/10.1097/WNF.0000000000000242 google scholar

9. Hadgu, R. M., Borghol, A., Gillard, C., Wilson, C., Elqess Mossa, S., McKay, M., Jastram Jr., C., & Onor, I. O. (2021). Evaluation of outcomes in patients receiving amantadine to improve alertness after traumatic brain injury. Hospital Pharmacy, 56(5), 486–494. https://doi.org/10.1177/0018578720920803 google scholar
10. Hughes, S., Colantonio, A., Santaguida, P. L., & Paton, T. (2005). Amantadine to enhance readiness for rehabilitation following severe traumatic brain injury. Brain Injury, 19(14), 1197–1206. https://doi.org/10.1080/02699050500309296 google scholar
11. Kalın, B. S., Sert, A. İ., Altun, K., & Öztürk, Ü. (2022). Can amantadine cause resistant hypernatremia in the treatment of hypoxic brain injury due to cardiac arrest? Turkish Journal of Nephrology, 31(4), 385–388. https://doi.org/10.5152/ turkjnephrol.2022.211295 google scholar
12. Khasanova, D. R., Saĭkhunov, M. V., Kitaeva, E. A., Khafiz'ianova, R., Islaamov, R. R., & Demin, T. V. (2009). Amantadine sulfate (PK-Merz) in the treatment of ischemic stroke: A clinical-experimental study. The Journal of Neurology and Psychiatry named after S.S. Korsakov, 109(5 Suppl 2), 37–43. google scholar
13. Krivonos, O. V., Amosova, N. A., & Smolentseva, I. G. (2010). Use of the glutamate NMDA receptor antagonist PK-Merz in acute stroke. Neuroscience and Behavioral Physiology, 40(5), 529–532. https://doi.org/10.1007/s11055-010-9292-6 google scholar
14. Leclerc, A. M., Riker, R. R., Brown, C. S., May, T., Nocella, K., Cote, J., Eldridge, A., Seder, D. B., & Gagnon, D. J. (2021). Amantadine and modafinil as neurostimulants following acute stroke: A retrospective study of intensive care unit patients. Neurocritical Care, 34(1), 102–111. https://doi.org/10.1007/s12028-020-00986-4 google scholar
15. Loggini, A., Tangonan, R., El Ammar, F., Mansour, A., Goldenberg, F. D., Kramer, C. L., & Lazaridis, C. (2020). The role of amantadine in cognitive recovery early after traumatic brain injury: A systematic review. Clinical Neurology and Neurosurgery, 194, Article 105815. https://doi.org/10.1016/j.clineuro.2020.105815 google scholar
16. Meythaler, J. M., Brunner, R. C., Johnson, A., & Novack, T. A. (2002). Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: A pilot double-blind randomized trial. The Journal of Head Trauma Rehabilitation, 17(4), 300–313. https://doi.org/10.1097/00001199-200208000-00004 google scholar
17. Naranjo, C. A., Busto, U., Sellers, E. M., Sandor, P., Ruiz, I., Roberts, E. A., Janecek, E., Domecq, C., & Greenblatt, D. J. (1981). A method for estimating the probability of adverse drug reactions. Clinical Pharmacology & Therapeutics, 30(2), 239– 245. https://doi.org/10.1038/clpt.1981.154 google scholar
18. Oommen, J. K., Wang, S., Axelrad, A., Hanna, A., Muralidharan, R., & Osias, J. (2019). Efficacy of modafinil, methylphenidate, amantadine, and zolpidem in consciousness recovery in intensive care unit patients with traumatic brain injury. PT: The Journal for Physical Therapy, 44(11), 676–681. google scholar
19. Peeters, M., Page, G., Maloteaux, J. M., & Hermans, E. (2002). Hypersensitivity of dopamine transmission in the rat striatum after treatment with the NMDA receptor antagonist amantadine. Brain Research, 949(1–2), 32–41. https://doi. org/10.1016/s0006-8993(02)02961-x google scholar
20. Salihoğlu, E., & Şahin, A. S. (2019). Can amantadine sulfate infusion be a life saver in intensive care unit? Turkiye Klinikleri Journal of Medical Sciences, 39(2), 129– 134. https://doi.org/10.5336/medsci.2018-62457 google scholar
21. Saniova, B., Drobny, M., Kneslova, L., & Minarik, M. (2004). The outcome of patients with severe head injuries treated with amantadine sulphate. Journal of Neural Transmission, 111(4), 511–514. https://doi.org/10.1007/s00702-004-0112-4 google scholar
22. Sawyer, E., Mauro, L. S., & Ohlinger, M. J. (2008). Amantadine enhancement of arousal and cognition after traumatic brain injury. The Annals of Pharmacotherapy, 42(2), 247–252. https://doi.org/10.1345/aph.1K284 google scholar
23. Stelmaschuk, S., Will, M. C., & Meyers, T. (2015). Amantadine to treat cognitive dysfunction in moderate to severe traumatic brain injury. Journal of Trauma Nursing, 22(4), 194–203. https://doi.org/10.1097/jtn.0000000000000138 google scholar