Revisiting Amantadine As a Treatment for Drug-induced Movement Disorders

Background: Amantadine, an aliphatic primary amine with complex actions on neurotransmitter systems in the basal ganglia, is approved for treating Parkinson's disease and drug-induced movement disorders (DIMDs). These disorders have a significant impact on clinical outcomes and quality of life in patients receiving antipsychotic treatment.

Methods: We searched PubMed up to June 1, 2019 to identify relevant studies. The following search terms were used: "amantadine" AND "dystonia," "parkinsonism, " "akathisia," "tardive dyskinesia," "catatonia," "neuroleptic malignant syndrome." Reference lists were reviewed for additional material.

Results: Evidence from multiple, small, controlled trials supports the efficacy of amantadine as a treatment for drug-induced parkinsonism. Studies show amantadine has a more favorable tolerability profile than anticholinergic medications in these patients. Clinical evidence from observational studies and case reports suggests that further trials might be warranted to support use of amantadine in select patients for preventing dystonic reactions and as a second-line agent for treating catatonia, neuroleptic malignant syndrome, and tardive dyskinesia. Evidence is lacking on the use of amantadine specifically for akathisia relative to other treatments.

Conclusions: Amantadine is an evidence-based pharmacologic strategy for treating drug-induced parkinsonism and might be an alternative treatment for other DIMDs in select patients. Additional randomized controlled trials are needed.