Efficacy and safety of amantadine as a treatment for apathy after brain injury: Two single-case experimental design studies

P.J.J. Spauwen*, Bert Ter Mors, Peter van Harten, Fleur Domensino, Rudolf Ponds, Caroline van Heugten

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

82 Downloads (Pure)


Studies on the efficacy of amantadine as a treatment for apathy after brain injury are scarce and of low quality. We examined the efficacy and safety of amantadine for treatment of apathy in two individuals with brain injury.

Two double-blind, randomized, single-case experimental (baseline-amantadine-placebo-withdrawal) design (SCED) studies. Apathy measures included a Visual Analogue Scale (VAS), the Neuropsychiatric Inventory (NPI) apathy subscale and the Behavior Rating Inventory of Executive Function for Adults "Initiate" subscale. Safety measures included a rating scale of possible side effects of amantadine and physical examinations.

No difference in apathy symptoms (VAS) between baseline and amantadine phase was found in case 1 (NAP = 0.55). Surprisingly, in case 2, apathy symptoms deteriorated from baseline to amantadine phase (NAP = 0.28, 90% CI = -0.69 to -0.20) and improved from amantadine to placebo phase (NAP = 0.92, 90% CI = 0.60-1.00). This improvement was also found on the NPI apathy subscale. Side effects of amantadine were observed in case 2.

In this SCED study, amantadine did not improve apathy symptoms in two individuals with brain injury. However, this study shows that side effects of amantadine can occur which lead to a significant decrease in well-being. More high quality studies are required.

Original languageEnglish
Pages (from-to)872-896
Number of pages25
JournalNeuropsychological Rehabilitation
Issue number6
Early online date30 Nov 2020
Publication statusPublished - 3 Jul 2022


  • Brain injury
  • Amantadine
  • Apathy
  • Single-case experimental design

Cite this