Effects of Methylphenidate on Cognitive Functioning

Author/Year/ Country/Study Design/ PEDro Score/N

Methods

Outcomes

Willmott et al. (2013)
Australia
RCT
PEDro=10
N=32

Population: TBI; Gender: Male=21, Female=11; Mean Time Post Injury=68d; TBI Val/Val Group (n=11): Mean Age=22.64yr; Mean GCS=4.67; TBI Val/Met Group (n=14): Mean Age=28.57yr; Mean GCS=5.38; TBI Met/Met Group (n=7): Mean Age=30.57yr; Mean GCS=6.83.
Treatment: Participants with TBI, in a crossover design, received 0.3mg/kg methylphenidate (2×/d) for 6 sessions in total (spanning 2wk), alternating between treatment and placebo for every other session. Results were compared against those from healthy controls (n=40).
Outcome Measures: Ruff 2 & 7 Selective Attention Test – automatic (2 & 7 ASRS) and controlled (2 & 7 CSRS), Selective Attention Task, Four Choice Reaction Time Task (4CRT) – dissimilar compatible (DC) and similar incompatible (SI), Symbol Digit Modalities Test (SDMT), Letter Number Sequencing Task, and Wechsler Test of Adult Reading.

  1. At baseline, there were no significant differences across various genotypes on attentional performance.
  2. Participants with TBI and Met/Met alleles performed significantly poorer on the SDMT (p<0.0005), 2 & 7 ASRS (p=0.001), 2 & 7 CSRS (p<0.0005), DC RT (p=0.005), and SI RT (p=0.002), when compared to controls. Analyses with participants with TBI and Val/Val alleles showed even worse outcomes, demonstrating poorer performance on 7/8 outcome measures.
  3. Following methylphenidate treatment one significant drug and genotype interaction was seen between Met/Met carriers and performance on the SDMT (F=4.257; p=0.024), suggesting Met/Met carriers were more responsive to methylphenidate than either the others.

Kim et al. (2012)
USA
RCT
PEDro=7
N=23

Population: Moderate/Severe TBI; Mean Age=34.2yr; Gender: Male=18, Female=5; Mean Time Post Injury=51.1mo.
Treatment: In a crossover design, participants were randomly assigned to receive 0.3mg/kg methylphenidate followed by placebo, or the reverse and were assessed after each.
Outcome Measure: Visual sustained attention task (VSAT) and two-back task.

  1. Relative to placebo, both accuracy (1.62±1.03 vs. 2.23±1.07; p<0.005) and mean reaction time (827.47±291.17s vs. 752.03±356.87s; p<0.05) in the VSAT were improved significantly on MPH.
  2. Relative to placebo, mean reaction time (929.31±192.92s vs. 835.02±136.12s; p<0.05), but not accuracy, in the two-back task was improved significantly when on MPH.

Willmott & Ponsford (2009)
RCT
PEDro=10
N=40

 

Population: TBI; Mean Age=26.93yr; Gender: Male=28, Female=12; Time since injury=68.38d.
Treatment: Patients received either methylphenidate (0.3mg/kg 2x/d, rounded to the nearest 2.5 mg) or a placebo. Patients were seen for 6 sessions across 2 week period. Patients then crossed-over.
Outcome Measure: Ruff 2 and 7 Selective Attention Test, Selective Attention Task, Four Choice Reaction Time Task, Sustained Attention to Response Task, Symbol Digit Modalities Test, Letter Number Sequencing Task, Wechsler Test of Adult Reading. 

  1. Methylphendiate significantly increased speed of information processing on the Symbol Digit Modalities Test (p=0.02); Ruff 2 and 7 Test-Automatic Condition (p=0.003); Simple Selective Attention Task (p=0.001); Dissimilar compatible (p=0.003), and Similar Compatible (p=0.002).

Pavlovskaysa et al. (2007)
Pre-Post
Israel
N=6

 

Population: TBI; Age Range=18-47yr; Gender: Male=4, Female=2; GCS ≥8.
Treatment: Participants were administered 5 to 10 mg of methylphenidate (MHP) over a 2 week period. Participants were evaluated before, during and after the administration of methylphenidate.
Outcome Measure: Performance on the visual spatial attention task analyzing rightward and leftward shifts of attention.

  1. Prior to treatment, patients were found to have great difficulty in shifting attention between hemifields.
  2. There was a significant improvement in the asymmetry with MHP (p<0.001).
  3. The right side performance was significantly better on average than the left side (0.77 vs. 0.59; p<0.05).
  4. Performance was significantly better for ipsilateral valid cueing (p<0.01) than for invalid cross-trials (p<0.001).
  5. The difference between ipsi- and cross-cueing for left side target performance is significant for each of the stags (p<0.001).

Kim et al. (2006)
Korea
RCT
PEDro=6
N=18

Population: TBI; Methylphenidate Group (n=9): Mean Age=30.1yr; Gender: Male=9, Female=0; Mean Time Post Injury=1.6yr; Placebo Group (n=9): Mean Age=38.3yr; Gender: Male=7, Female=2; Mean Time Post Injury=3.6yr. 
Treatment: Patients were randomly allocated to receive either 20mg methylphenidate or the placebo. Assessments were done at baseline (T1), 2hr post treatment (T2), and 2d later (T3). 
Outcome Measure: Visual sustained attention task (VSAT) and two-back task.

  1. At T1 there were no significant differences in mean reaction time or in accuracy between the two groups.
  2. For those in the treatment group, the mean reaction time of the two-back task improved significantly compared to those in the placebo group from T1 to T2 (13.74±13.22% vs. 4.02±9.48%; p<0.05).
  3. No significant difference in improvement as seen with accuracy of the two-back task (p=0.07), nor with the VSAT.

Whyte et al. (2004)
USA
RCT
PEDro=8
N=34

Population: TBI; Mean Age=37yr; Gender: Male=29, Female=5; GCS<12; Median Time Post Injury=3.2yr.
Treatment: Participants received 0.3mg/kg/dose methylphenidate for 3wk, 2×/d, and placebo for 3wk, for a total of 6wk, with conditions alternating weekly. Washout lasted a day, after which time the groups crossed over. 
Outcome Measure: Attention Tasks.

  1. Methylphenidate showed significant improvements in information processing speed (p<0.001), work task attentiveness (p=0.01), and caregiver attention ratings (p=0.01), pre-post.
  2. No treatment-related improvements were observed in susceptibility to distraction, and divided or sustained attention.

Plenger et al. (1996)
USA
RCT
PEDro=5
N=23

Population: TBI; Gender: Male=17, Female=6; Placebo Group (n=13): Mean Age=26.6yr; Mean GCS=8.1; Methylphenidate Group (n=10): Mean Age=31.4yr; Mean GCS=9.3.
Treatment: Patients were randomly allocated to receive either methylphenidate or placebo. Methylphenidate was administered at 30mg/kg, 2×/d, for 30d.
Outcome Measure: Disability Rating Scale (DRS), Continuous Performance Test (CPT), 2 & 7 Test (2 & 7), Paced Auditory Serial Addition Test (PASAT), Digit Span & Attention/ Concentration from Wechsler Memory Scale-Revised (Attn/Conc from WMS-R).

  1. At 30d follow-up (n=15), significant differences were obtained on DRS, suggesting better outcome for the methylphenidate group. This difference however was not seen at 90d follow-up (n=11).
  2. Significant differences were found on the attention-concentration domain at the 30d follow-up, as indicated by CPT, PASAT, 2 & 7, and Attn/Conc from WMS-R (p<0.03). The treatment group performed better in these measures compared to the placebo group.

Speech et al. (1993)
USA
RCT
PEDro=7
N=12

Population: TBI; Mean Age=27.6yr; Gender: Male=5, Female=7; Mean Time Post Injury=48.5mo.
Treatment: In a crossover design, participants were randomly assigned to receive 0.3mg/kg methylphenidate, 2×/d, for 1wk, followed by 1wk of placebo, or receive the treatment in a reverse order.
Outcome Measure: Gordon Diagnostic System, Digit Symbol and Digit Span subtests of the Wechsler Adult Intelligence Scale-Revised, Stroop Interference Task, Sternberg High Speed Scanning Task, Selective Reminding Test, Serial Digit Test, and Katz Adjustment Scale.

  1. No significant differences were found between methylphenidate and placebo condition in any of the outcome measures studied.