Table Appendices: (Table 7.7)

Pharmaceutical Treatments

Individual Studies

Table 7.7Pharmaceutical Therapiesto Enhance Cognitive-Communication Skills

Methylphenidate

Author/Year/ Country/Study design/PEDro & D&B Score

 

Methods

 

Outcome

Kim et al., (2006)

Korea

RCT

D&B = 17

PEDro = 6

N=18Double-blind placebo-controlled trial of subjects with TBI. The participants were randomly divided into one of two treatment groups: (1) single-dose (20mg) of methylphenidate; or (2) placebo. Outcome measured using visuospatial attention tasks.

Improvements in response accuracy were demonstrated in favour of the treatment group although not to a level of statistical significance.

Donezepil

Author/Year/ Country/Study design/PEDro & D&B Score

 

Methods

 

Outcome

Zhang et al.,

(2004)

USA

RCT

PEDro = 7

D&B = 23

 

N=18 Individuals with a history of TBI of any severity with attention or short-term memory impairments as shown by WMS III, and PASAT were randomly assigned to treatment group A (received donezepil orally for 10 weeks, followed by a 4 week washout period, followed by 10 weeks of a placebo) and group B (opposite order as group A). Outcomes measured at baseline, wk 10 and wk 24. There were no statistical differences between groups at baseline.

Group A (donepezil phase) showed significant improvement over group B (placebo phase) on immediate auditory (p=0.002) and visual memory (p<0.001) measures of WMS-III and PASAT (p<0.001) at wk 10. Increased scores in Group A were continued following washout. Group B improved following donepezil phase (wk 24)– but inter-group comparisons were not significant (audio: p=0.588; visual: p=0.397, PASAT presentation rates p=0.545, 0.12, 0.783, 0.410) due to Group A’s sustained high scores.

Bromocriptine

Author/Year/ Country/Study design/PEDro & D&B Score

 

Methods

 

Outcome

Whyte et al.,

(2008)

USA

RCT

PEDro=7

D&B=22

N=12Bromocriptine or placebo was administered for 4 weeks, (starting dose was 1.25 mg/BID, final dose was 5 mg/BID).  Medication was increased every 2 days until the dose reached 5 mg BID. During week 4 the medication was tapered until it was eliminated.  Once this phase was complete the group was put on the placebo.  The placebo group then became the bromocriptine group. Study continued for about 8 weeks. During the study participants encaged in various attention tasks: Sustained arousal and attention task (50/50), sustained arousal and attention task (20/80), speed/accuracy trade off task, distraction task, choice RT task, dual task, sustained attention to response to task, test of every day attention, inattentive behaviour task, classroom attentiveness, attention ratings.

It was noted that several participants did experience moderate to severe drug effects and withdrew or were withdrawn from the study.  Test results for all subjects indicate bromocriptine had little significant effect on their abilities to perform on a range of measures of attentional function.

McDowell et al., (1998)

USA

RCT

PEDro = 4

D&B = 16

 

N=24Subjects suffering a TBI (closed or open) with loss of consciousness (GCS < 8).  Patients randomized into treatment (Bromocriptine 2.5 mg) and placebo groups.  Measures required prefrontal cortex function (working memory, executive control) and were administered using a laptop computer (except trail making and control task) Testing took place 90 minutes after pill administration. 

Central executive testing: following drug treatment there were significant improvements on dual task counting (p=0.028), dual task digit span (p=0.016), trail making test (p=0.013), Stroop Interference Test (p=0.05), FAS Test (p=0.02), Wisconsin Card Sorting (p=0.041). The treatment drug had no significant effects on working memory tasks (p=0.978), or control tests (p=0.095).

Amantadine

Author/Year/ Country/Study design/PEDro & D&B Score

 

Methods

 

Outcomes

Schneider et al.,

(1999)

USA

RCT

D&B = 18

PEDro= 5

N=20TBI rehabilitation subjects randomly assigned to treatment and placebo groups to test the effectiveness of amantadine on cognitive and behavioural rehabilitation.

Although there was a general trend towards improvement, results did not reach significance when treatment and placebo groups were compared using ANOVA and regression analysis (p=0.732).

Citicoline

Author/Year/ Country/Study design/PEDro & D&B Score

Methods

Outcomes

Zafonte et al.,

(2012)

USA
RCT

PEDro=8

D&B=26

N=1213 Individuals who had sustained a TBI (Mild to Severe) were recruited for the study. Participants were randomly assigned to the treatment group, receiving 200 mg/day of citicoline or a placebo. All were placed on the medication for 90 days.

At the 90 day evaluation, no differences were found between the two groups. Results from the GOS-E showed equal improvement in both groups. Results from the remaining test also showed similar levels of improvement between the groups.

Overall, Citicoline was not found to be more effective in improving function and cognitive status then the placebo regardless of level of injury (mild to severe).

PEDro = Physiotherapy Evidence Database rating scale score (Moseley et al., 2002).

D&B = Downs and Black (1998) quality assessment scale score.