Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury

Abstract

We report findings from a 12-week randomized double-blinded placebo-controlled trial of methylphenidate or galantamine to treat emotional and cognitive complaints in individuals (n = 32) with a history of PTSD, TBI, or both conditions. In this small pilot study, methylphenidate treatment was associated with clinically meaningful and statistically significant improvement compared with placebo on the primary outcome, a measure of cognitive complaints (Ruff Neurobehavioral Inventory-Postmorbid Cognitive Scale), as well as on the secondary outcomes reflecting post-concussive (Rivermead Post Concussive Symptom Questionnaire) and post-traumatic stress symptoms (Posttraumatic Stress Disorder Checklist). Treatment was well tolerated. These results suggest the need for a larger RCT to replicate and confirm these findings. Design considerations for such a trial should include the need for multiple sites to facilitate adequate recruitment and extension of the treatment and follow-up periods.

The effect of single-dose methylphenidate on the rate of error-driven learning in healthy males: a randomized controlled trial

“…MPH may have the potential to correct this deficit by accelerating the adaptation of error-driven learning to environmental volatility. Supporting this, a recent multicenter randomized controlled trial found that treatment with MPH was associated with a remarkably robust reduction in symptoms of posttraumatic stress disorder (PTSD) (McAllister et al 2015). Future research can incorporate functional neuroimaging along with the computational approach described here in order to assess the influence of MPH on the dACC-LC circuit both in normal individuals and individuals with anxiety disorders.…”

Galantamine and Environmental Enrichment Enhance Cognitive Recovery after Experimental Traumatic Brain Injury But Do Not Confer Additional Benefits When Combined

“…[39][40][41] Therapeutically, GAL is associated with improved episodic memory and amelioration of depressive symptoms in TBI patients. 42 GAL has also been shown to improve cognitive function in patients with Alzheimer's disease and mild cognitive impairment. [43][44][45][46][47][48] Moreover, a substantial proportion of patients who failed to recover with donepezil exhibited benefits when switched to GAL, suggesting that previous failures in responding to certain AChEIs do not predict responses to others, such as GAL.…”

Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial

“…As has been noted in related literature, despite the need for interventional studies to address cognitive problems after TBI, recruitment for this and similar studies is extremely challenging (McAllister et al, 2015). The initial target for this study was to recruit 50 patients into each treatment group, for a total of 200 participants.…”

“…Evidence suggests that MPH improves performance on measures of attention, memory, verbal fluency, processing speed, motor performance, and arousal, and is also associated with improvements in subjective (self or informant) assessment of cognitive functioning (Gualtieri and Evans, 1988;Johansson et al, 2015;Kaelin et al, 1996;McAllister et al, 2015;Plenger et al, 1996;Whyte et al, 1997;Whyte et al, 2004;Whyte et al, 2002;Willmott and Ponsford, 2009). Indeed, the Defense and Veterans Brain Injury Center's Neurobehavioral Guidelines Working Group evidence-based review of pharmacotherapies for post-traumatic cognitive impairments recommended MPH at the Guideline level for attention and processing speed impairments, and at the Option level for general cognitive deficits and memory impairments (Warden et al, 2006).…”