Zhang et al.

(2004)

USA

RCT

PEDro=7

N=18

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

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

Outcome Measures: Auditory (AII) and Visual (VII) subtests of Wechsler Memory Scale-III, and the 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>0.1) 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<0.05), as well as in PASAT (p<0.001), after receiving donepezil.

Campbell et al.

(2018)

United States

PCT

N=129

Population: Donepezil Group (N=55): Mean Age=34.4yr; Gender: Male=80%, Female=20%; Mean time post injury=28.6d; Injury Severity=Moderate-severe. Control Group (N=74): Mean Age=40.8yr; Gender: Male=71.6%, Female=28.4%; Mean time post injury=25.2d; Injury Severity=Moderate-severe.

Intervention: Individuals were assigned to receive either donepezil or a placebo treatment for an average of 67.5 days. Those receiving donepezil started with a dosage of 5mg/day, increasing to 10mg/day over the course of 7-10 days. Follow-up assessments took place approximately 61.4 days after treatment.

Outcome Measures: Trail Making Tests (Part A and B), Digit Span index (DS), California Verbal Learning Test-II (CVLT-II), Logical Memory II (LMII), Functional Independence Measure (FIM), Disability Rating Scale (DRS).

1.        For both parts of the Trail Making Test (Part A and B), there was a significant effect of time (p<0.001, p<0.001) respectively. Demonstrating that both groups significantly improved over time. No other significant effects were found for the Trail Making Test.

2.        Likewise, in the DS, only a significant effect of time (p<0.001) was observed.

3.        For both the learning and memory components of the CVLT-II there was only a significant effect of time observed (p<0.001, p<0.001).

4.        The LMII showed similar results with only a significant effect of time observed (p=0.005).

5.        For measures of disability, both the DRS and the FIM also only showed a significant effect of time for both groups respectively (p<0.001, p<0.001).

6.        Overall, there were no significant effects of treatment found, however both groups did demonstrate significant spontaneous recovery.

Khateb et al.

(2005)

Switzerland

Pre-Post

N_initial=15, N_final=10

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

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

Outcome Measures: Stroop test, Trail Making Test (TMT), Rey Auditory Verbal Memory Test (RAVMT) and 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=0.03); for learning and memory the RAVMT-learning (47.7±6.9 to 53.5±5.0, p=0.05); and for attention, the errors subsection of divided attention (5.8±3.3 to 2.9±2.7, p=0.03).