Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Abstract

Abstract-Pharmacological management of neurobehavioral disorders following traumatic brain injury (TBI) is common practice. However, the evidence available to guide this practice remains sparse. This review summarizes, in brief, the state of knowledge, organized via a time continuum from injury as well as by symptom complex. The areas of neuroprotection, hypoarousal, attention and memory deficits, aggression, agitation, depression, and mania are reviewed. The literature was searched with PubMed on the terms "traumatic brain injury" or "brain injury" with "pharmacology" (and the symptoms according to which this review is arranged). Additional searches were conducted with the specific symptoms as search terms, crossed with the therapeutic agents or drug classes discussed. Where a paucity of prospective data exists, case reports and retrospective studies are included. Studies to date have yielded minimal positive evidence for enhancing function, memory, and behavior after TBI. No single agent likely will become sentinel in the recovery process, and combination therapy in the acute and postacute settings are required. A need exists to further define the role of psychopharmacology in postacute TBI medicine and the specific characteristics of subpopulations who might benefit.

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

“…GAL was associated with improved episodic memory, also consistent with previous work in other populations such as Alzheimer's disease where this agent is FDA approved for treatment of the episodic memory problems that are the hallmark of that disorder. This profile of cognitive enhancement with these two agents is consistent with the proposed neurobiology of underlying mechanisms of cognitive complaints and deficits in TBI (McAllister and Arciniegas, 2002;Arciniegas, 2006;Chew and Zafonte, 2009), and the shared neurobiological underpinnings of symptom overlap in TBI and PTSD (Stein and McAllister, 2009).…”

Treatment for depression following mild traumatic brain injury in adults: A meta-analysis

“…Thus, there is a clear need for large randomised controlled trials of treatment for depression after mild TBI. Overall, the findings from the current meta-analysis support the conclusions of previous reviews, that is, there is insufficient evidence to TREATMENT FOR DEPRESSION AFTER MILD TBI 14 recommend a particular type of treatment for depression after mild TBI (Warden, Gordon et al 2006;Chew and Zafonte 2009;Fann, Hart et al 2009). …”

“…The only treatment showing an effect greater than zero was methylphenidate (Lee, Kim et al 2005), whilst treatment with amitriptyline was less effective that placebo (Saran 1985;Dinan 1992). Other studies have indicated that methylphenidate was effective in improving attention post-TBI particularly processing speed and sustained attention (Chew and Zafonte 2009) which may mediate the improvement in depression symptoms, however its widespread use following TBI tends to be limited due to its potential to lower seizure thresholds.…”

“…Commonly used psychological and pharmacological treatments for major depressive disorder have been used to treat depression post-TBI but the effectiveness of these interventions is equivocal (Alderfer, Arciniegas et al 2005;Chew and Zafonte 2009). The Neurobehavioural Guidelines Working Group (Warden, Gordon et al 2006) suggest the use of amitriptyline, desipramine and sertraline, even though they note a lack of evidence to support any specific recommendations.…”

Detection of Structural and Metabolic Changes in Traumatically Injured Hippocampus by Quantitative Differential Proteomics

“…The field now has a rich description of the events and processes that have been implicated in TBI, including inflammation, edema/ischemia, oxidative stress, excitotoxicity, neurogenesis, angiogenesis, synaptogenesis, endogenous stem cells, and glial scar formation using traditional reductionistic experimental approaches. 8,9,22,25,40,43,52,58,63,74,75 Comprehensive and integrative approaches to investigate these diverse mechanisms have only been described recently and to a limited extent. The value of an unbiased, global, systems biology analysis of dysregulated protein expression is well-documented and often provides novel insights into information processing that occurs at a higher level of emergent principles than can be appreciated from the analysis of a handful of signaling molecules in isolation.…”