October 2009
Reviewer: Jeff C. Huffman, MD
Depression and cognitive complaints following mild traumatic brain injury
Background: This is a useful clinical/review article about the pathophysiology, evaluation, and
treatment of mood and cognitive complaints among patients who suffer traumatic brain injury
(TBI). Treatment of TBI-associated neuropsychiatric syndromes has become an area of increasing
interest and importance, given our growing knowledge about the functional impact of these
syndromes and the elevated incidence of TBI among returning veterans.
Results/Discussion: I will review the basic tenets outlined in the paper (more specific details are
available in the article)
Pathophysiology: The pathophysiology of mood and cognitive problems after TBI is complex.
Mechanical brain/neuronal injury can, in humans, theoretically result in: (a) a cytotoxic "cascade" that includes dysregulation of calcium/magnesium, free radical formation, and proteolysis, ultimately causing neuronal cell death; and (b) disruptive elevations in neurotransmitters, including glutamate, with potentially longer-term/chronic dysfunction of systems involving acetycholine, dopamine, norepinephrine, and serotonin.
In terms of implicated brain regions, these abnormalities (e.g., cytotoxicity and abnormal neurotransmitter levels) in frontal and temporal lobes and brainstem/thalamic areas are often associated with the development of neuropsychiatric syndromes related to TBI.
Evaluation of patients for TBI: Evaluation of patients for post-TBI syndromes begins with an assessment to determine whether a TBI occurred — i.e., whether there was an event resulting in physical force or serious acceleration/deceleration forces to the brain, with resultant and immediate alteration in mental status or focal neurological deficit. This evaluation often relies heavily on objective data (e.g., medical records and other reports) and collateral information (e.g, from family), given that patients suffering TBI may not recall the timing of events or symptoms immediately after an injury. If a TBI did occur, it is then important to carefully characterize associated mood, cognitive, and physical symptoms, and to assess whether current mood or cognitive symptoms occurred after the TBI, rather than being premorbid.
Management of depression following TBI: The first steps for management of any patient with TBI include education about TBI, counseling about potential symptoms and prognosis, and rehabilitation interventions; these steps may reduce the risk of persistent symptoms. Regarding depression, the authors opine that standard diagnostic criteria should be used and that when the mood symptoms meet criteria for depression and impair function, treatment for depression should be initiated. There is evidence supporting the use of citalopram and sertraline for post-TBI depression; other standard agents are also likely to be effective, but one must be cautious with agents that may have drug-drug interactions (e.g., fluoxetine), anticholinergic effects (e.g., TCAs and to a lesser degree paroxetine), or increase risk of seizure (e.g., immediate release bupropion). Methylphenidate might be helpful as an adjunct, especially if there are residual cognitive symptoms or apathy.
Management of cognitive disturbances following TBI: Management of post-TBI cognitive disturbance includes the basic steps above regarding education and rehabilitation interventions. Cognitive rehabilitation, in particular, can help patients to develop compensatory strategies for cognitive deficits. Pharmacologic therapy with psychostimulants (especially for slowed cognition and poor arousal) and cholinesterase inhibitors (especially for memory impairment) provide benefit.