Amantadine and memantine: a comprehensive review for acquired brain injury

ABSTRACT

This comprehensive review discusses clinical studies of patients following brain injuries (traumatic, acquired, or stroke), who have been treated with amantadine or memantine. Both amantadine and memantine are commonly used in the acute rehabilitation setting following brain injuries, despite their lack of FDA-approval for neuro-recovery. Given the broad utilization of such agents, there is a need to review the evidence supporting this common off-label prescribing. The purpose of this review is to describe the mechanisms of action for memantine and amantadine, as well as to complete a comprehensive review of the clinical uses of these agents. We included 119 original, clinical research articles from NCBI Medline, published before 2019. We focused on the domains of neuroplasticity, functional recovery, motor recovery, arousal, fatigue, insomnia, behavior, agitation, and cognition. Most of the existing research supporting the use of amantadine and memantine in recovery from brain injuries was done in very small populations, limiting the significance of conclusions. While most studies are positive; small effect sizes are usually reported, or populations are subject to bias. Furthermore, evidence is so limited that this review includes research regarding both acute and chronic acquired brain injury populations. Fortunately, reported short-term side effects generally are modest, and stop soon after amantadine/memantine is discontinued. However, responses are inconsistent, and the phenotype of responders remains elusive.

KEYWORDS:

• Acquired brain injury
• amantadine
• memantine

Declaration of Interest

Dr. Ma reports no declarations of interest. Dr. Zafonte reports that he received royalties from: 1) Oakstone for authorship of an educational CD; 2) Demos Publishing for serving as co-editor of the text Brain Injury Medicine. Dr. Zafonte serves on the Scientific Advisory Board of Myomo, Oxeia Biopharma, ElMINDA and Biodirection.

Addendum

Search terms:

Concept1A (428 results)"Amantadine"[Mesh] OR Amantadin*[tiab] OR Aminoadamantane[tiab] OR Adamantylamine[tiab] OR Wiregyt[tiab] OR Amanta[tiab] OR AmantaSulfateAZU[tiab] OR Amixx[tiab] OR Cerebramed[tiab] OR GenAmantadine[tiab] OR “Infecto Flu” [tiab] OR InfectoFlu[tiab] OR Infex[tiab] OR Midantan[tiab] OR PMSAmantadine[tiab] OR Symadine[tiab] OR Symmetrel[tiab] OR Endantadine[tiab] OR Mantadix[tiab] OR tregor[tiab] OR Viregyt[tiab] OR Adekin[tiab] OR Aman[tiab]—- ORConcept 1B (3314 results)"Memantine"[Mesh] OR Memantin*[tiab] OR dimethyladamantane[tiab] OR Namenda[tiab] OR Ebixa[tiab] OR Axura[tiab]——ANDConcept 2A (174656 results)“Stroke” [Mesh] OR Cerebrovascular[tiab] OR CVA[tiab] OR Apoplexy[tiab] OR “Vascular Accident”[tiab]

—– OR

Concept 2B (267399 results)

“brain injuries” [Mesh] OR “brain Injury” [tiab] OR “brain laceration” [tiab] OR hypoxia[tiab] OR hypoxic[tiab] OR anoxic[tiab] OR concussion[tiab] OR “Commotio Cerebri” [tiab] OR encephalopathy[tiab]

Yielding 193 results, manually removed articles that were not original research (reviews and opinion papers) to reach the final 119 papers included.