Zhang et al.

(2004)

USA

RCT

PEDro=7

N=18

Population: TBI; Group A (n=9): Mean Age=33 yr; Gender: Male=6, Female=3; Mean GCS=9.3; Mean Time Post Injury=4.6 mo; Group B (n=9): Mean Age=31 yr; Gender: Male=7, Female=2; Mean GCS=8.9; Mean Time Post Injury=3.9 mo.

Intervention: In a randomized crossover trial, Group A received oral donepezil for the first 10 wk, followed by a washout period of 4 wk. At the conclusion of the washout period, patients received a placebo for 10 wk. Group B received the treatments in the opposite order. Donepezil was administered at 5 mg/d for the first 2 wk, and at 10 mg/d for the remaining 8 wk.

Outcome Measures: Auditory (AII) and Visual (VII) subtests of Wechsler Memory Scale-III, Paced Auditory Serial Addition Test (PASAT).

1.        At week 10, Group A achieved significantly better scores in AII (95.4±4.5 versus 73.6±4.5; p=0.002), VII (93.5±3.0 versus 64.9±3.0; p<0.001), and in the PASAT (p≤0.001) compared to Group B.

2.        This increase in scores in Group A were sustained after washout and placebo treatment (week 24), leading to no significant differences in AII (105.9±4.5 versus 102.4±4.5; p=0.588), VII (91.3±3.0 versus 94.9±3.0; p=0.397), and PASAT (p>0.100) compared to Group B at study end.

3.        Within-group comparisons showed that patients in both Group A and Group B improved significantly in AII and VII (p<0.050), as well as in PASAT (p<0.001), after receiving donepezil.

Khateb et al.

(2005)

Switzerland

Pre-Post

N_initial=15

N_final=10

Population: TBI; Mean age=43 yr; Gender: Male=8, Female=7; Mean Time Post Injury=42 mo.

Intervention:  Patients were administered donepezil 5 mg/day for 1mo, followed by 10 mg/day for 2 mos.

Outcome Measures: Stroop test, Trail Making Test (TMT), Rey Auditory Verbal Memory Test (RAVMT), Test for Attentional Performance (TAP).

1.        4 of 15 participants stopped due to side effects within the first week (e.g., nausea, sleep disorders, anxiety, dizziness, etc.).

2.        Changes on the neuropsychological evaluation show modest improvement, the comparison of the global score of all questionnaires before and after therapy was marginally significant (p=0.058).

3.        A significant improvement in executive function was only found for the Stroop Colour naming test (87.3±22.9 to 79.5±19.1, p=0.030); for learning and memory the RAVMT-learning (47.7±6.9 to 53.5±5.0, p=0.050); and for attention, the errors subsection of divided attention (5.8±3.3 to 2.9±2.7, p=0.030).

Morey et al.

(2003)

USA

Case Series

N=7

Population: TBI; Mean Age=30.7 yr; Gender: Male=5, Female=2; Mean Time Post Injury=33.3 mo.

Intervention: Following baseline cognitive testing (T1), each participant began a 6mo treatment phase with 5 mg/d donepezil for the first 4 wk, then with 10 mg/d for the final 5 mo (T2). Washout period then occurred for 6 wk (T3). Another 6-mo treatment period took place with participants receiving 5 mg/d donepezil for the entire period (T4).

Outcome Measures: Brief Visual Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test, digit span and letter-number sequence subtests of Wechsler Adult Intelligence Scale-Revised III, Controlled Oral Word Association Test, Memory Functioning Questionnaires.

Masanic et al.

(2001)

Canada

Pre-Post

N=4

Population: TBI; Age Range=24-35 yr; Gender: Male=4, Female=0; GCS Range=3-8; Time Post Injury Range=35-46 mo.

Intervention: Participants received 5mg donepezil daily for 8 wk, followed by 10mg daily for 4 wk. Washout period then occurred for 4 wk. Assessments occurred at baseline, and at weeks 4, 8, 12, and 16.

Outcome Measures: Rey Auditory Verbal Learning Test (RAVLT), Complex Figure Test (CFT), Rivermead Behavioural Memory Test (RBMT).

1.        Mean scores for short-term and long-term recall on the RAVLT improved by 1.03 (1.25±1.89 at baseline to 3.00±2.70 at week 12) and 0.83 (0.50±0.58 at baseline to 2.50±2.38 at week 12) standard deviations above baseline, respectively.

2.        Mean scores for short-term and long-term recall on the CFT improved also by 1.56 (13.88±8.45 at baseline to 20.13±12.93 at week 12) and 1.38 (14.00±5.60 at baseline to 19.38±11.46 at week 12) standard deviations above baseline, respectively.

3.        Perceived memory deficit (RBMT) showed a trend toward improvement over the first 12wk, followed by deterioration after the washout period.