US Pharm. 2014:39(1):20-23.

In the United States, traumatic brain injury (TBI) is a common cause of death and disability.1 Of those patients admitted to head injury units, between 9% and 14% are over the age of 65 years, and this group has the worst prognosis.2 Causes of TBI include transportation-related causes (e.g., motor vehicle and bicycle accidents, collisions with pedestrians), falls (especially in senior adults and young children), physical assaults, and sports activities.1 Repetitive brain trauma, as seen in persons who have engaged in contact sports and participated in the military, is associated with progressive neurologic deterioration in some individuals.3 An overview of TBI and chronic traumatic encephalopathy (CTE), a neurodegenerative disease thought to be caused in part by TBI and in its later stages associated with dementia, is discussed below. The role of the pharmacist may be of particular benefit when resistant headache in an elderly person requires pharmaceutical intervention beyond simple analgesia.  


TBI is physical injury to brain tissue that temporarily or permanently impairs brain function; various types include1:

Concussion: A transient and reversible posttraumatic alteration in mental status (e.g., loss of consciousness or memory) a concussion may last from seconds to minutes, but by arbitrary definition, <6 hours. Symptoms, referred to as postconcussion syndrome, include nausea, headache, dizziness, and memory disturbance and may cause temporary disability and have an impact on physical, emotional, cognitive, and social domains.

Brain contusions: These are bruises of the brain secondary to open or closed injuries. Brain function impairment can occur based on contusion size and location and cancause brain edema and increased intracranial pressure (ICP). Enlargement of a contusion can occur within hours or days after injury, and neurologic deterioration may ensue.

Diffuse axonal injury: As seen in shaken baby syndrome, diffuse axonal injury results in generalized, widespread disruption of axonal fibers and myelin sheaths. Associated edema increases ICP.  

Hematomas: Collections of blood in or around the brain that may occur with open or closed injuries, hematomas may be epidural, subdural, or intracerebral. Subarachnoid hemorrhage (SAH) is common in TBI, with a different appearance from aneurysmal SAH as seen on computed tomography (CT). A consideration pharmacists should be aware of when reviewing the medication regimen of a senior with TBI is that selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed medications in the U.S., and while the SSRI-associated elevated risk for hemorrhage has been small, it is especially linked to concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) or warfarin.4,5,6

Skull fractures: These are penetrating injuries, although closed injuries may also cause skull fractures. Some skull fractures may cause damage to the middle and inner ear structures and may impair nerve function (i.e., facial, acoustic, and vestibular).  


In the first few days after a moderate or severe injury, maintaining adequate brain perfusion and oxygenation and preventing and treating complications of altered sensorium are important.1 While many patients require rehabilitation subsequent to traumatic head injury, those with mild injuries are discharged and observed.1 The following effects may be encountered by clinicians in a variety of practice settings:  


Posttraumatic headache is frequently a conspicuous feature of closed head injury, without regard to whether consciousness is lost.7 The appearance of symptoms (TABLE 1) usually occurs within a day or so following injury and may persist for months. In some cases, there may be difficulty in obtaining information about headache in the early phase after return of consciousness, owing to the presence of concomitant medications that may affect pain perception.8 CT scan or MRI of the head usually does not show abnormal findings. CT brain scan should be reserved for those with focal signs or fluctuating consciousness.9 Optimistic encouragement and rehabilitation (based on occupational circumstances) are advised; frequently, symptoms resolve spontaneously within several months.7


While treatment with simple analgesics such as acetaminophen or the NSAID ibuprofen may show positive therapeutic outcomes, the increased risk of intracranial bleeding post head trauma should be considered, as well as the NSAID’s ability to alter platelet function and prolong bleeding time. If headaches are severe, prophylactic treatment of migraine may be necessary; treatment options may include antiepileptic agents such as topiramate (50 mg orally twice daily) and off-label valproic acid (250-500 mg orally twice daily); off-label amitriptyline (e.g.10-150 mg orally per day); beta blockers such as propranolol (80-240 mg orally divided twice to four times daily) and timolol (10-30 mg orally per day); calcium channel blockers (CCBs) such as verapamil (80-240 mg orally divided three times daily); or others (e.g., onabotulinumtoxinA injected IM by a trained clinician).7,10,11 Of note, amitriptyline is associated with considerable sedation, anticholinergic effects, orthostasis, and conduction abnormalities, which may be especially problematic in the elderly and in those with certain medical histories and comorbidities (e.g., myocardial infarction [MI], stroke, tachycardia, conduction abnormalities). Furthermore, sedative effects may be additive with other central nervous system (CNS) depressive agents and/or alcohol. Owing to its CNS penetration and nonselective action, propranolol may not be the beta-blocker of choice for use in the elderly. CCBs do not cause significant CNS effects, which may be an advantage over some other agents.11 Resistant headache may require psychological management and the use of psychotropic agents.9

Clinicians should refer a patient with a headache in the following circumstances: 1) acute onset reported as “worst headache in my life”; 2) history of trauma, hypertension, fever, or visual changes; 3) increasing headache unresponsive to basic measures; and 4) the presence of neurologic signs or tenderness of the scalp. The patient should be admitted to the hospital if SAH is suspected.7


Traumatic vertigo is most commonly caused by concussion of the labyrinth. Symptoms generally diminish within several days of incident but may persist for up to a month or more. If a skull fracture traverses the inner ear, severe vertigo usually results and may last several days to a week; deafness in the involved ear usually ensues. Chronic posttraumatic vertigo pre-sents clinically as episodic positioning vertigo. Management of this condition consists of 1) supportive care; 2) vestibular suppressant medication (e.g., meclizine or diazepam, which may cause confusion and increase the risk of falls in the elderly); and 3) vestibular rehabilitation, a therapy involving exercises designed to retrain the brain to recognize and process signals from the vestibular system and coordinate them with information from vision and proprioception (see RESOURCES).12,13

Neck injury may induce cervical vertigo triggered by neck movements. Diagnosis may be confused with migraine-associated, head movement–induced vertigo.12,14 Cervical vertigo is managed with neck movement exercises as permitted by orthopedic considerations.12,14

Head trauma may also precipitate episodic vertigo with or without migraine-type headache. Visual and motion sensitivity, auditory sensitivity, photosensitivity, and head pressure may accompany the vertigo. Foods triggering migrainous vertigo include caffeine, chocolate, and alcohol; stress, anxiety, and sleep deprivation may exacerbate symptoms. Management consists of dietary and lifestyle modifications (avoiding triggers, reducing stress, improving sleep) and prophylactic antimigraine medication therapy.7,12,15-17

Hearing and Vision Loss  

Following simple concussion, some degree of sensory hearing loss may occur; after skull fracture, hearing loss is a frequent occurrence. Hearing loss has also been associated with the deployment of air bags during an automobile accident. Following moderate or severe concussion, vision is rarely altered or lost, and symptoms usually resolve spontaneously over weeks to months; acute traumatic blindness seldom resolves after 3 to 4 months.1,12,18  

Olfactory Dysfunction  

Head trauma is responsible for <5% of cases of hyposmia, reduced sense of smell; it is more frequently associated with anosmia, the loss of smell.12 Posttraumatic anosmia seldom resolves after 3 to 4 months.1 (Of note, the subject of olfactory dysfunction in the neurologic disorders Parkinson disease and Alzheimer disease is a recent research focus.) Many medications can contribute to olfactory dysfunction, including systemic or inhaled drugs (e.g., aminoglycosides); many other medications and compounds may alter smell sensitivity, including alcohol, nicotine, organic solvents, and directly applied zinc salts.19 Endocrine disturbances commonly seen in the elderly (e.g., hypothyroidism, diabetes mellitus) may affect olfactory function as well.19

While there is no specific treatment recommended for primary disruption of olfaction, clinicians may discuss supportive measures with patients, including 1) use of spices (e.g., pepper) to stimulate the trigeminal and olfactory chemoreceptors; 2) avoiding overuse of table salt for seasoning; 3) use of smoke alarms for safety; and 4) replacing gas appliances with electric ones for safety. 12,20-22  

Posttraumatic Seizures  

Trauma-induced seizures can occur in patients of any age; however, they are an especially important cause in young adults.7 Since seizures can worsen brain damage and increase ICP, prompt treatment is warranted. It is not necessarily implied that if seizures appear within the first week following injury, future seizures will occur; if the dura mater has been penetrated, however, posttraumatic epilepsy is more likely to develop, manifesting within 2 years after injury.1,7 In a small percentage of patients, late seizures (>7 days after the injury) develop often weeks, months, or even years following injury.1

While there is at present no definitive evidence that the use of prophylactic anticonvulsant medication therapy reduces the incidence of posttraumatic epilepsy, a prophylactic anticonvulsant (e.g., phenytoin, fosphenytoin) should be considered in patients with significant structural injury (e.g., larger contusions or hematomas, brain laceration, depressed skull fracture) or a Glasgow Coma Scale (GCS) score <10 (see RESOURCES).1,7  

Duration of treatment depends on the type of injury and EEG results; if no seizures develop within one week, anticonvulsants should be discontinued since their benefit in preventing future seizures is not established.1  

Other Associated Symptoms  

Other symptoms may occur following moderate or severe concussion, including fatigue, difficulty concentrating, amnesia (variable), anxiety, apathy, and depression; gait and balance disturbances, spastic motor impairment, and ataxia can also occur.1 Except in elderly patients, hemiparesis and aphasia usually resolve at least to some extent.1  

Cognitive and neuropsychiatric deficits can persist, especially if structural damage was significant; long-term symptoms include amnesia (retrograde and anterograde), behavioral changes (e.g., agitation, impulsivity, disinhibition, lack of motivation), emotional lability, sleep disturbances, and decreased intellectual function.1 Of note, disability in social relations and employment are attributed more to cognitive deficits and various personality changes than focal motor or sensory impairments.1

In some cases, a TBI may result in a persistent vegetative state with preservation of autonomic and motor reflexes and normal sleep-wake cycles, while self-awareness and other mental activity are absent.1 Normal neurologic function rarely returns after a vegetative state lasting 3 months after injury; after 6 months, almost no patients recover.  

Neurologic function may continue to improve for a few years after TBI, but is most rapid during the initial 6 months.1 For a detailed discussion of TBI including management based on the severity of injury, see Reference 1.  


Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is thought to be partially caused by repetitive symptomatic concussive and asymptomatic subconcussive brain injury.3,23,24 While repetitive brain trauma appears necessary for the development of CTE, it is not solely the cause of the disease.3 Originally referred to as dementia pugilistica, CTE has long been known to affect boxers and has recently been confirmed in other athletes, including retired professional football players.24,25 Recent research suggests that CTE is more likely to occur as a result of repeated mild injuries, rather than one or two severe ones. 25,26  

Further, according to recent postmortem findings, CTE may affect a broader population than was initially conceptualized, particularly among contact sport athletes and those with a history of military combat.3 Researchers Baugh et al indicate that given the large population that could potentially be affected, CTE may represent an important issue in public health.3 Additional risk factors that may also play a role in the development of CTE and require further research include 1) longer duration of exposure to head trauma; 2) age at first exposure; and 3) genetic predisposition.3

Neuropathologic changes in various areas of the brain occur, including tissue degeneration and a buildup of abnormal tau protein (referred to as tau tangles), which are also found in patients with Alzheimer disease.23,24 Researchers have noted that CTE has a clear environmental etiology.25

The neuropsychologic and neuropsychiatric symptoms associated with this disorder—generally beginning years or decades after repeated brain trauma and suggesting it during an individual’s lifetime—fall into three categories3:

Cognitive changes: learning and memory impairment; executive dysfunction such as planning, organizing, multitasking, and judgment early in the course of disease; dementia late in the course  

Mood changes: depression, apathy, irritability, and suicidality  

Behavioral changes: poor impulse control (e.g., described as having a “short fuse” or being “out of control”), aggression, increased violence, disinhibition, and problems with substance and other forms of abuse.  

Symptoms worsen later in the course of CTE; later stages are associated with dementia. Currently, there are no validated clinical diagnostic criteria or biomarkers for CTE, and like other forms of dementia, it cannot be officially diagnosed until autopsy.3 Some patients with CTE have been noted to have a concomitant neurodegenerative disease, such as Alzheimer disease, frontotemporal dementia (FTD), Lewy body disease, or Parkinson disease. Researchers observe that CTE may not produce the same changes in all patients; it does not progress at the same rate in all patients, and it may not progress at all in some individuals.26  


Pharmacists should be aware of TBI as an important issue in older adults in light of the cognitive, mood, and behavioral changes that may occur. In addition to providing accessible, cost-effective, and high-quality pharmaceutical care services, pharmacists can enhance their role in the community as patient advocates and community educators to seniors and their caregivers, as well as to veterans, students, parents, and athletes, by raising awareness of the risks associated with head injury and CTE.

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