Table 1.

MPH interventions in adults with a history of TBI ranging from mild to severe (see ClinicalTrials.gov).

Study title and identifier	Brief description	Design and study population	Treatment schedule	Outcome measures	Study results and limitations
Cognitive remediation after trauma exposure trial = CREATE Trial (CREATE) NCT01416948	To evaluate the efficacy of MPH and galantamine in the treatment of persistent cognitive symptoms associated with PTSD and/or TBI	Randomized, double-blind, placebo-controlled, parallel assignment; adults with mild to moderate TBI and/or PTSD	MPH 20 mg b.i.d., or galantamine 12 mg b.id., or placebo for 12 weeks	RNBI, RPSQ, RAVLT, TMT, subtests of WAIS-III, BVMT-R, PASAT, CPT, PTSD Checklist—specific event version, and Patient Health questionnaire-9	Study was terminated due to lack of recruitment-−32 participants out of proposed 159; Limitation- mixed TBI/PTSD population
Dopamine receptor imaging to predict response to stimulant therapy in chronic TBI NCT02225106	To evaluate PET imaging with [11C]-raclopride, a D2/D3 receptor ligand, before and after administering MPH, to measure endogenous dopamine release in TBI patients with problems in cognition, attention, and executive function	Non-randomized one-time placebo and one-time MPH, after that MPH for 4 weeks; adults with moderate to severe TBI	MPH 60 mg one-time, after that 30 mg b.i.d.; 4 weeks	CVLT, TMT, Subtests of the WAIS-IV, RPSQ, Sustained arousal and attention task 50/50; Dual task; Distraction task; Sustained attention to response, and Test of everyday attention	Study was completed with actual enrollment of 11 out of proposed 30; No results available; Limitations- small sample size, no randomization
MPH (Ritalin) and Memory/Attention in traumatic brain injury (TBI) NCT00453921	To compare the results of three interventions: memory and attention training, MPH, and memory/attention training in combination with MPH and use functional MRI to characterize changes in activation of the neural circuitry of memory and attention in study groups	Randomized, double-blind, placebo-controlled, parallel assignment; adults with mild to severe TBI	MPH 0.3 mg/kg b.i.d.; 7 weeks	CVLT, CPT, and Functional MRI task performance and brain activation (N-back)	All p < 0.05; Limitations- small sample size (18–20 participants in each group), wide range of TBI severity, and no info regarding participants' distribution of TBI severity
The relationship between traumatic brain injury and dopamine (a chemical in the brain) NCT02015949	To investigate if treatment with MPH improves cognitive functions in TBI, whether the mechanism involves a normalization of brain functioning and whether brain dopamine levels (measured by the SPECT and MRI) can predict the magnitude of any improvement in symptoms.	Randomized, cross-over, placebo controlled; adults ≥3 months post- moderate to severe TBI	MPH 0.3 mg/kg b.i.d. or placebo for 2 weeks	CRT and relationship of CRT to specific binding ratio of the dopamine transporter (DAT) in the striatum. Patients were divided into low vs. normal DAT level based on their DAT binding ratio on SPECT.	All participants completed trial (n = 40, 20 assigned to each MPH-placebo sequence). CRT was reduced (faster) in the low DAT subgroup while on MPH as compared to placebo; fatigue improved when on MPH.

MPH, methylphenidate; TBI, traumatic brain injury; b.i.d., bis in die (latin) or two times a day; BVMT-R, Brief Visuospatial Memory Test-Revised; CPT, Continuous Performance Test; CRT, Choice Reaction Time task; CVLT, California Verbal Learning Test; MRI, Magnetic Resonance Imaging; RAVLT, Rey Auditory Verbal Learning Test; RNBI, Ruff Neurobehavioral Inventory—Post-morbid Cognitive Scale; RPSQ, Rivermead Post-concussion Symptom Questionnaire; PASAT, Paced Auditory Serial Addition Test; PTSD, post-traumatic stress disorder; SPECT, Single Photon Emission Computed Tomography; TMT, Trail Making Test; WAIS, Wechsler Adult Intelligence Scale.