Systematic Review on Norepinephrine and Dopamine Reuptake Inhibitors for Traumatic Brain Injury-Related Symptoms: Report of the American Congress of Rehabilitation Medicine.

Abstract

To evaluate the efficacy of mixed norepinephrine and dopamine reuptake inhibitors (NDRI) on cognitive and non-cognitive neuropsychiatric outcomes following traumatic brain injury (TBI), and to describe their safety/tolerability. A literature search using MEDLINE® and a reference title search were conducted from inception to August 17 2023. Studies were retained based on prespecified, PICO framework criteria: (1) participants were aged 18 years or older with mild, moderate or severe TBI; (2) an NDRI class medication was studied [e.g. methylphenidate hydrochloride (MPH)]; (3) the research design included a comparison group; (4) the treatment sample size was ≥9; and (5) cognition, emotion, behavior, or safety/tolerability was an outcome. Trained methodologists extracted information. Each study's scientific quality was classified using procedures in the 2017 American Academy of Neurology Guideline Development and Process Manual; articles with Class I-III evidence ratings were retained. Thirteen articles from 442 identified publications met review criteria. Sufficient evidence was available to evaluate MPH. Meta-analysis generated pooled effects and 95% confidence intervals for outcome domains. MPH improved performance on objective measures of processing speed (k = 9, d = 0.39 [95% CI: 0.17, 0.60), selective attention (k = 5, d = 0.33 [95% CI: 0.04, 0.61]), and sustained attention (k = 4, d = 0.45 [95% CI: 0.11, 0.79]). MPH reduced clinician-evaluated depressive symptoms (k = 2, d = 1.06 [95% CI: 0.47, 1.64). MPH did not produce adverse events or clinically significant autonomic dysfunction. There was little evidence that time since injury and injury severity moderated MPH effects. Among adults with TBI, MPH has medium effects on selective attention, sustained attention, and processing speed, and large effects on depressive symptoms. These effects are consistent with MPH's biological mechanisms and are not moderated by injury severity or time since injury.