Donepezil for Cognitive Deficits Following Traumatic Brain Injury: A Case Report

A 36-year-old male with a history of alcohol/drug abuse was struck by a train and suffered multiple fractures including a basilar skull fracture. CT revealed pneumocranium and infarct in the left lenticular nucleus. In the first 2 months of hospitalization, he experienced delirium while in the intensive care unit; following recovery from delirium he exhibited dysphoria and cognitive deficits. His mother had died early in his hospitalization, but he was unable to learn this fact despite being told several times. Medications at the time of psychiatric consultation (2 months after admission) included metoclopramide, benazepril, metoprolol, hydrocodone, morphine sulfate, and chloral hydrate.

Mental status testing revealed mild dysarthria, irritable dysphoria, concrete thought processes, and neither violent ideations nor psychosis. Mini-Mental State Examination (MMSE) score was 18, with deficits in orientation, recall, and concentration. The patient was started on donepezil 5 mg/day. In 10 days, his MMSE score improved to 23. Venlafaxine 75 mg/day and risperidone 0.5 mg bid were added. Doses were adjusted to donepezil 10 mg/day, venlafaxine 150 mg/day, and risperidone 2 mg qhs. Over the next 30 days, his MMSE score improved to 28, his dysphoria improved, and he was better able to remember his accident. He was finally able to learn of his mother's death. He was able to complete physical rehabilitation. On clinic follow-up he remained stable with an MMSE score of 29.

Cardenas et al.¹ compared physostigmine to scopolamine in traumatic brain injury. Forty-four percent of physostigmine subjects showed improved memory on neuropsychological measures. Taverni et al.² treated 2 traumatic brain injury cases with donepezil 5 mg/day with improvement in memory. Whelan et al.³ treated 53 head injury patients with donepezil 5 to 10 mg/day for up to 2 years. IQ and clinician-based ratings showed improvement. Masanic et al.⁴ studied donepezil 5 to 10 mg/day on 4 chronic traumatic brain injury patients and found improved memory and fewer disturbances in behavior. Whitlock⁵ reported 9 outpatients with memory impairment treated with donepezil (7 with traumatic brain injury); 3 showed 5 or more points of improvement on the MMSE.

Our patient exhibited amnesia for 8 weeks before the trial of psychotropic medications. It is challenging to distinguish amnesia from depression and delirium in the head trauma patient. Initially, we attributed some of his cognitive symptoms to depression and/or delirium. It is difficult to attribute clinical improvement to any one psychotropic medication in such a case. Mood, arousal, and attention have an intimate connection with cognition, but the sequence of interventions suggests a contribution of donepezil to improved cognition. Even small improvements in orientation, concentration, and memory can be of functional significance.

Physicians encountering traumatic brain injury patients may consider anticholinesterase agents in concert with other psychotropic agents. Large, prospective trials of anticholinesterase agents for traumatic brain injury with cognitive deficits are desirable to quantify the effects of this intervention.