Central Acetylcholinesterase Inhibitors in the Treatment of Chronic Traumatic Brain Injury-clinical Experience in 111 Patients

Purpose: Theoretically, central acetylcholinesterase inhibitors (CAIs) could alleviate at least some of the main symptoms of chronic traumatic brain injury (TBI). The aim of this report is to describe clinical experience of the treatment of chronic TBI with these drugs.

General Methods: From an outpatient clinic material, 111 patients were selected having chronic stable TBI with at least one of the following target symptoms: fatigue, poor memory, diminished attention or diminished initiation. Patients received in random donepezil, galantamine or rivastigmine. The evaluation of the treatment response was based on the subjective view of the patient.

Findings: As first treatment, 27 patients received donepezil, 30 galantamine and 54 rivastigmine. Altogether 41 patients tried more than one drug, but only three patients tried all three alternatives. In total, 61% of patients had a marked positive response and 39% a modest or no response. The clearest effect was in almost all responders a better vigilance and attention causing better general function. About half of the patients (55%) wanted to continue therapy with one of these drugs. The therapeutic response became very quickly and at low doses. There were no significant differences between the three drugs either in effect or tolerability. The age, sex, type of injury, severity of TBI or elapsed time after injury did not affect the response. The mean dose in maintenance therapy was 7.2 mg od for donepezil, 5.0 mg bid for galantamine and 2.3 mg bid for rivastigmine. Side effects or inadequate therapeutic response were the main causes for discontinuation with nearly equal frequency. Paradoxical responses were seen in some patients.

Conclusions: CAIs show a very promising therapeutic potential in the treatment of chronic TBI. There were no significant differences between the three drugs. Large-scale randomised double-blinded placebo-controlled studies are clearly needed.