Innov Clin Neurosci. 2017;14(3–4):11
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality. Annually, more than two million people in the United States will sustain a TBI, and approximately one quarter of those will require hospitalization. Of those who survive TBI, many continue to suffer from a variety of symptoms, including low energy, lack of emotional arousal, poor memory, attention/concentration deficits, mood lability, agitation, irritability, aggressiveness, and depression.
Case report. A 58-year-old man with a history of TBI presented for an outpatient appointment with complaints of difficulty functioning in his daily routine. In particular, he reported difficulties in getting out of bed, showering, doing volunteer work or holding a job, and an inability to spend meaningful time with his 11-year-old daughter. He endorsed a lack of focus and concentration, depression, low energy level, and feelings of hopelessness. He denied feelings of guilt or worthlessness. He also acknowledged a few episodes of transient suicidal ideations without a specific plan for a duration of 30 minutes. These episodes occurred about twice week and were extremely intense at times. The patient reported no problems with sleep or appetite. He denied any symptoms of mania and psychosis.
Five years earlier, the patient sustained TBI without a loss consciousness. Since that time, he began experiencing moderate to severe depressive symptoms, anxiety, and cognitive deficits, eventually leading to an economic hardship due to inability to maintain employment. Prior to this incident, he had no history of emotional, psychiatric, substance abuse issues.
At the moment at his examination, the patient was treated with a combination of paroxetine 30mg at bedtime, bupropion XL 300mg daily, mixed salts of a single-entity amphetamine (Adderal XR®) 20mg twice daily, and zolpidem 10mg at bedtime with only minimal therapeutic response. After the risks and benefits of changes in his treatment were explicitly discussed, a therapeutic trial of modafinil was initiated, starting at 100mg daily. Augmentation with modafinil (300mg daily) was associated with significant improvements in depressive symptoms, particularly a reduction in suicidal ideations, and greater ability to participate in activities of daily living. Specifically, the patient estimated that his abilities to participate in all activities daily living increased by more than 50 percent. Augmentation with modafinil was well tolerated.
Discussion. TBI results in a complex alteration of various brain regions. Recent advances in neuroimaging studies support the hypothesis that symptomatology of TBI-induced depression and cognitive deficits are directly related to the altered functional connectivity between different brain networks. The default mode network represents one of them. It has been previously proposed that this functional network mainly consists of the ventromedial prefrontal cortex, posterior cingulate/retrosplenial cortex, and inferior parietal lobule. The neurochemical underprint of this network is modulated by a combined input from cortical and subcortical catecholamine systems.
Modafinil is a United States Food and Drug Administration (FDA)-approved wakefulness-promoting agent with a direct effect on synaptic levels of norepinephrine (NE) and dopamine (DA). The proposed mechanism of actions of modafinil is related to its ability to inhibit the NE and DA transporters. In addition, modafinil indirectly effects extracellular levels of serotonin, glutamate, orexin, histamine, and gamma-aminobutyric acid. With these considerations, the clinical relevance of catecholamine modulation was examined in different populations of patients with depressive symptoms and cognitive deficits.[5,6] Our patient’s robust response provides further support for the safety and efficacy of modafinil use as an adjunct agent in patients with TBI.
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Oleg V. Tcheremissine, MD, and James C. Rachal, MD
Carolinas Healthcare System, Department of Psychiatry, Charlotte, North Carolina
The authors have no conflicts of interest relevant to the content of this letter. No funding was received for the preparation of this letter.