Evidence-Based Reviews

Traumatic brain injury: Choosing drugs to assist recovery

Current Psychiatry. 2006 May;5(5):57-68

Some agents can worsen neurobehavioral symptoms.

References

1. American Academy of Neurology. Practice parameter: The management of concussion in sports. Neurology 1997;48:581-5.

2. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2(7872):81-4.

3. Alexander MP. Mild traumatic brain injury: Pathophysiology, natural history, and clinical management. Neurology 1995;45:1253-60.

4. Arlinghaus KA, Shoaib AM, Price TRP. Neuropsychiatric assessment. In: Silver JM, McAllister TW, Yudofsky SC (eds). Textbook of traumatic brain injury. Arlington, VA: American Psychiatric Press; 2005:59-78.

5. Hagen C, Malkmus D, Durham P. Communication Disorders Service, Rancho Los Amigos Rehabilitation Hospital, Downey, CA, 1972 (rev. 1997).

6. Diagnostic and statistical manual of mental disorders (4th ed, text rev). Washington, DC: American Psychiatric Association; 2000.

7. McCrory P. Does second impact syndrome exist? Clin J Sport Med 2001;11:144-9.

8. Vagnozzi R, Signoretti S, Tavazzi B, et al. Hypothesis of the postconcussive vulnerable brain: experimental evidence of its metabolic occurrence. Neurosurgery 2005;57:164-71.

9. Marin RS, Chakravorty S. Disorders of diminished motivation. In: Silver JM, McAllister TW, Yudofsky SC (eds). Textbook of traumatic brain injury. Arlington, VA; American Psychiatric Press; 2005:337-52.

10. Goldstein LB. Prescribing of potentially harmful drugs to patients admitted to hospital after head injury. J Neurol Neurosurg Psychiatry 1995;58:753-5.

11. Phillips JP, Devier DJ, Feeney DM. Rehabilitation pharmacology bridging laboratory work to clinical application. J Head Trauma Rehabil 2003;18:342-56.

12. Stanislaw SL. Cognitive effects of antipsychotic agents in persons with traumatic brain injury. Brain Injury 1997;11:335-41.

13. Rao N, Jellinek HM, Woolston DC. Agitation in closed head injury: haloperidol effects on rehabilitation outcome. Arch Phys Med Rehabil 1985;66:30-4.

14. Feeney DM, Gonzalez A, Law WA. Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science 1982;217:855-7.

15. Wilson MS, Gibson CL, Hamm RJ. Haloperidol, but not olanzapine, impairs cognitive performance after traumatic brain injury in rats. Am J Phys Med Rehabil 2003;82:871-9.

16. Goldstein LB, Davis JN. Clonidine impairs recovery of beamwalking after a sensorimotor cortex lesion in the rat. Brain Research 1990;508:305-9.

17. Brailowsky S, Knight RT, Efron R. Phenytoin increases the severity of cortical hemiplegia in rats. Brain Research 1986;376:71-7.

18. Boyeson MG, Harmon RL. Effects of trazodone and desipramine on motor recovery in brain-injured rats. Am J Phys Med Rehabil 1993;72:286-93.

19. Hernandez TD, Holling LC. Disruption of behavioral recovery by the anticonvulsant phenobarbital. Brain Research 1994;635:300-6.

20. Schallert T, Hernandez TD, Barth TM. Recovery of function after brain damage: severe and chronic disruption by diazepam. Brain Research 1986;379:104-11.

21. Deb S, Crownshaw T. The role of pharmacotherapy in the management of behavior disorders in traumatic brain injury patients. Brain Injury 2004;18:1-31.

22. Campbell JJ, Duffy JD. Treatment strategies in amotivated patients. Psychiatric Annals 1997;27(1):44-9.

23. Evans RW, Gualtieri CT, Patterson D. Treatment of chronic closed head injury with psychostimulant drugs: a controlled case study and an appropriate evaluation procedure. J Nerv Ment Dis 1987;175:106-10.

24. Elovic EP, Lansang R, Li Y, Ricker JH. The use of atypical antipsychotics in traumatic brain injury. J Head Trauma Rehabil 2003;18:177-95.

25. Lombard LA, Zafonte RD. Agitation after traumatic brain injury: considerations and treatment options. Am J Phys Med Rehabil 2005;84:797-812.

26. Pachet A, Friesen S, Winkelaar D, Gray S. Beneficial behavioural effects of lamotrigine in traumatic brain injury. Brain Injury 2003;17:715-22.

27. Boyeson MG, Harmon RL, Jones JL. Comparative effects of fluoxetine, amitriptyline, and serotonin on functional motor recovery after sensorimotor cortex injury. Am J Phys Med Rehabil 1994;73:76-83.

28. Khateb A, Ammann J, Annoni JM, Diserens K. Cognition enhancing effects of onepezil in traumatic brain injury (abstract). Eur Neurol 2005;54:39-45.

29. Zhang L, Plotkin RC, Wang G, et al. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil 2004;85:1005-55.

30. Walker W, Seel R, Gibellato M, et al. The effects of donepezil on traumatic brain injury acute rehabilitation outcomes. Brain Inj 2004;18:739-50.

Choosing medications for patients with traumatic brain injury (TBI) requires caution; some drugs slow their recovery, and no standard post-TBI treatment exists.

As consulting psychiatrist on a TBI rehabilitation team, I am asked to manage enduring cognitive and emotional problems—aggression, apathy, learning disabilities, dementia—in patients with moderate to severe head injuries. This article describes how we apply available evidence to treat neurobehavioral symptoms in these patients.

Case: An iraq war casualty

The physical medicine and rehabilitation service asks for help in managing agitation, anxiety, and nightmares in Mr. N, age 20, a U.S. combat soldier. While on patrol 2 months ago in Iraq, he suffered a penetrating right frontoparietal brain injury from an improvised explosive device.

Mr. N has undergone a right temporoparietal craniectomy with debridement, ventriculostomy placement, and scalp flap closure. He has had seizures and then pancreatitis—thought to be caused by divalproex prescribed to treat the seizures. Divalproex was replaced with phenytoin at our hospital, and the pancreatitis resolved.

How serious an injury?

TBI ranges from self-limited concussion to devastating, permanent CNS impairment and life-long disability. Brain injuries from sudden impact—from assaults, falls, motor vehicle accidents, combat, or sports—can cause diffuse axonal injury and confusion or unconsciousness, even without radiographic evidence of cerebral bleeding, edema, or mass effect.

No hierarchy or nomenclature is universally accepted for TBI. The term “concussion” is generally used for milder injury and TBI for more-severe injuries.

Concussion. The American Academy of Neurology defines concussion as a trauma-induced alteration in mental status that may or may not involve loss of consciousness. Confusion and amnesia—the hallmarks of concussion—may occur immediately after the head trauma or several minutes later.¹ This definition recognizes three concussion grades:

Grade 1: confusion lasts
Grade 2: confusion persists >15 minutes but without LOC
Grade 3: concussion with LOC. The confusional state is marked by disorientation, delayed verbal and motor responses, inattention, incoordination, emotional lability, and slurred or incoherent speech.

TBI. The severity of an injury with LOC is usually determined by four factors: the patient’s initial Glasgow Coma Scale (GCS) score in the emergency department (Table 1),² neuroimaging, duration of coma, and duration of posttraumatic amnesia (PTA).

Mild TBI: GCS 13 to 15, LOC 1,3
Moderate TBI: GCS 9 to 12, LOC 30 minutes to 7 days, and PTA 24 hours to 7 days.
Severe TBI: GCS ≤8, LOC, and PTA >7 days,⁴ or any focal neuroimaging abnormalities.³

Table 1

Using Glasgow Coma Scale scores to evaluate brain injury severity

Component	Response	Score
Best eye response	No eye opening	1
	Eye opening to pain	2
	Eye opening to verbal command	3
	Eyes open spontaneously	4
Best verbal response	No verbal response	1
	Incomprehensible sounds	2
	Inappropriate words	3
	Confused	4
	Oriented	5
Best motor response	No motor response	1
	Extension to pain	2
	Flexion to pain	3
	Withdrawal from pain	4
	Localizing pain	5
	Obeys commands	6
GCS total score ≥12 is mild injury, 9 to 11 is moderate, and ≤8 is severe (90% of patients with scores ≤8 are in a coma). Coma is defined as not opening eyes, not obeying commands, and not saying understandable words. Composite scores with eye, verbal, and motor responses (such as E3V3M5) are clinically more useful than totals.
Source: Reference 2.

Case continued: ‘They’re hurting me’

Mr. N meets criteria for severe TBI. He is periodically agitated and aggressive and refuses to return to physical therapy, complaining that rehabilitation nurses are intentionally hurting him. He occasionally hits the staff and throws things. His medications include:

phenytoin, 100 mg every 6 hours for seizure prophylaxis
lamotrigine, 50 mg bid for seizure prophylaxis
zolpidem, 5 mg as needed at bedtime for pain
methadone, 10 mg/d for pain
oxycodone, 5 mg every 4 hours as needed for breakthrough pain.

Mr. N’s recovery 2 months after injury is rated as Rancho level IV, indicating that he remains confused and agitated. He requires maximal assistance with bed mobility and transfers, upper and lower extremity dressing, and rolling his wheelchair with both feet. He is incontinent of bowel and bladder.

Assessing progress

For patients such as Mr. N, TBI recovery progress is measured with the Rancho Los Amigos Scale.

The original Rancho scale—developed in 1972 by staff at the Rancho Los Amigos rehabilitation hospital in Downey, CA—described eight levels of cognitive and adaptive functioning, from coma and total care through normal cognition and independence. A 1997 revised version separates the highest cognitive functioning level (VIII, purposeful, appropriate function) into three parts, expanding the scale to 10 levels (Table 2).⁵

Of course, not all TBI patients begin recovery at Rancho level I, and unfortunately not all achieve level X. Some experience dementia caused by head trauma, with persistent memory impairment and cognitive deficits in language, apraxia, agnosia, or executive function.⁶