Oral physostigmine and impaired memory in adults with brain injury

The purpose of this study was to examine the effects of physostigmine, a cholinergic agonist, on memory loss after traumatic brain injury (TBI), as compared to placebo or scopolamine, a cholinergic antagonist, using a double-blind, placebo-controlled design. Each subject received each active drug and placebo. Neuropsychological measures (Wechsler Memory Scale I and II, Selective Reminding Test, Trail-Making Test, Parts A and B, Digit Symbol, and Memory Questionnaire) and measures of clinical balance were completed at baseline, after each drug phase, and at 1 month follow-up. Thirty-six subjects completed the study with results showing an improvement in memory scores in 44% of subjects (responders) while taking oral physostigmine. The most sensitive measure was the Selective Reminding Test, specifically Long-term Storage. The impact of drugs on standing balance as compared to placebo was improved standing time in the responders: (1) with physostigmine when standing tandem with eyes closed (p < 0.05), and (2) with scopolamine when standing on one foot with eyes closed (p < 0.05). Results support the potential benefit of cholinergic agonists on memory after TBI and the need for further research of possible clinical markers for the drug.