Traumatic brain injury: Choosing drugs to assist recovery

Most patients recover as predicted by the initial injury’s severity. Others experience diffuse cerebral swelling with sudden, rapid deterioration after what appeared to be a grade 1 or grade 2 concussion. Diffuse cerebral swelling is sometimes considered a “second-impact syndrome,” but it can also occur after a single impact.⁷ A second TBI is not universally believed to cause the precipitous decline, but animal studies suggest an additive effect of rapid sequential TBI.⁸

Table 2

10-level Rancho Los Amigos Scale for assessing TBI recovery

Recovery for a patient such as Mr. N with Rancho level IV to V TBI may be complicated by marked mood lability, spontaneous aggression, psychomotor agitation, extremely short attention with marked distractibility, little to no short-term memory, and noncooperation with treatment and care. Patients may also show disorders of diminished motivation, characterized by normal consciousness but decreased goal-directed behavior and affective flattening.⁹

Case continued: Calling in reinforcements

Besides combat nightmares, Mr. N is experiencing other signs of posttraumatic stress disorder (PTSD): intrusive memories of dead comrades, anhedonia, insomnia, irritability, and hypervigilance. We recommend a trial of citalopram, 10 mg/d, but within 1 week he becomes more irritable, agitated, and aggressive, with worsening sleep. We arrange a meeting to obtain collateral information from Mr. N’s aunt, mother, and clinical psychologist. We learn that a first-degree relative had bipolar disorder, and Mr. N lived with various relatives during childhood.

As a child, Mr. N was easily angered, hyperactive, unpredictably aggressive with peers, and impulsive. He was diagnosed with “explosive disorder” at age 8. A psychiatrist prescribed methylphenidate (which helped) and paroxetine (which worsened his behavior and aggression). Based on this history, we make a presumptive diagnosis of comorbid bipolar disorder.

Treating psychopathology

Comorbidities. Adolescents and adults with pre-existing attention-deficit/hyperactivity disorder or bipolar disorder may be predisposed to carelessness or risk taking that lead to accidents and TBI. Likewise, alcoholism and substance use disorders are risk factors for head injuries. These pre-existing conditions will complicate the post-TBI course and must be treated concurrently.

Depression and PTSD may follow a head injury and complicate recovery. In fact, post-TBI symptoms—poor sleep, poor memory and concentration, and irritability—are common to both depression and PTSD.

A team approach. Regardless of its severity or recovery stage, TBI requires multidisciplinary treatment. Physical, occupational, and speech therapies are essential initially. As recovery progresses, vocational rehabilitation may need to be added. Throughout rehabilitation, supportive individual and family therapy can help patients reintegrate into the community. Psychologists, neuropsychologists, and clinical social workers are indispensable to the treatment team.

Medication precautions

Using medications to manage post-TBI syndromes is difficult and controversial. No standard regimen exists, and few clinical trials guide treatment. Small, uncontrolled studies (human and animal) suggest commonly prescribed drugs may worsen outcomes (Table 3).^10,11 For example:

• Cognitive function improved in three TBI patients after thioridazine was discontinued in two and haloperidol in one.¹²
  
• Haloperidol given to 11 patients with TBI made no difference in rehabilitation outcomes when compared with 15 patients who did not receive the antipsychotic. Those receiving haloperidol also had longer post-trauma amnesia (5 to 30 weeks), compared with the untreated group (1 to 18 weeks).¹³
  
• In animal studies of TBI, motor recovery was slowed with haloperidol but not olanzapine,^14,15 and with clonidine,¹⁶ phenytoin,¹⁷ and trazodone.¹⁸ Phenobarbitol.¹⁹ and diazepam²⁰ have been associated with delayed behavioral recovery and chronic behavior problems, respectively, in rats with TBI. How these agents might affect human patients is speculative.
  

Medications with potential to impede TBI recovery*

• Psychostimulants have improved recovery of motor function in animal trials if given before physical therapy.¹⁴
  
• Stimulants and dopaminergic agonists such as bromocriptine and amantadine might help disorders of diminished motivation.²²
  
• Dextroamphetamine and methylphenidate have improved impulsivity, memory, and concentration in a patient with TBI.²³