Oral physostigmine and impaired memory in adults with brain injury

Abstract

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.

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

“…Physostigmine was shown in a placebo-controlled study, to improve verbal long-term storage and retrieval in 4 percent of 36 subjects with TBI with severe memory impairment [78]. Another study combining physostigmine with lecithin did not show an improvement with measures of memory [77].…”

“…One study comparing physostigmine/lecithin to lecithin alone in 16 subjects with moderate to severe TBI with memory deficits found no difference in measures of attention and memory between the two treatment groups, apart from improved sustained attention on the continuous performance test when physostigmine was initiated first in the crossover design [77]. A double-blind, placebocontrolled study comparing the effect of physostigmine, placebo, and scopolamine on attention and memory in 36 subjects found improvement in scores on one measure of attentional processes in the physostigmine group [78].…”

Ethical questions in functional neuroimaging and cognitive enhancement

“…These include people with ADHD Mehta et al 2000;Turner et al 2004a, as well as patients with schizophrenia (Turner et al 2004b) and frontotemporal dementia (Rahman et al 2005). Patients with cognitive impairments resulting from traumatic brain injury have also been shown to derive some benefit from pharmacological treatment (Cardenas et al 1994;McDowell et al 1998). …”

Call for an Integrative and Multi-Disciplinary Approach to Traumatic Brain Injury (TBI)

“…The psychostimulant, dextroamphetamine, may also have the added benefit of reducing the variability in performance in tasks of attention and working memory (Hornstein, Lennihan, Seliger, Lichtman, & Schroeder, 1996), but the studies at this time are limited. Cholinesterase inhibitors, initially developed in treating dementia, as donepezil and physostigmine, have been useful in treating the memory deficits and improving attention following TBI (Cardenas et al, 1994;Griffin et al, 2003;Taverni, Seliger, & Lichtman, 1998;Zhang et al, 2004). Other drugs in this pharmacological class as, rivastigmine and galantamine, as well as, other drugs used in treating dementia, as the NMDA antagonist, memantine, need to be more systematically studied in future studies.…”