WORKUP	Section 5 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Imaging Studies:

• Other than collecting hospital records and neuropsychological testing, specialized workup may require the following:

• Serial sleep-deprived electroencephalograms can be used to diagnose seizures, and a quantitative EEG may show abnormalities in postconcussive syndrome.

• CT scan performed 1-3 months after injury may detect cerebral contusions not visible immediately.

• MRI scans are more sensitive than CT scans in demonstrating DAI and frontal and temporal lesions.

• Single-photon emission computed tomography (SPECT) scan is a relatively accessible form of functional imaging that, in the future, may prove the most sensitive measure of white matter lesions. Further research is needed to correlate such lesions with their clinical effects.

Other Tests:

• Neuropsychological testing is the most reliable way to document and quantify cognitive impairments following head injury.

Histologic Findings: The pathophysiology of CHI results from contusions and DAI. DAI occurs in high-velocity trauma, especially trauma with an element of twisting or rotation. The shearing forces of impact cause axons to stretch and break. Disruption of axons triggers a cascade of further insults, including calcium influx, excitotoxin release, phospholipase activation, and lipid peroxidation (see

Staging: Head injury severity is rated based on the GCS and the GOAT results. Severity of sequelae may be rated on the Ranchos Los Amigos Cognitive Scale or the Neurobehavioral Rating Scale.

	TREATMENT	Section 6 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical Care: This article does not discuss the treatment of patients with acute head injury during the period of coma and PTA.

Both the patient who has become demented and one who has developed PCS benefit from psychological support and education with the following, when indicated: (1) behavioral modification, (2) cognitive rehabilitation, (3) psychotropic medication for specific syndromes or symptoms, (4) family or network intervention, (5) social services, and (6) medical support in legal proceedings.

Psychological intervention with patients with head injuries shares the goals of all psychotherapy—instilling and maintaining hope, supporting mastery, and helping the patients arrive at an adaptive meaning for their experience. Patients benefit from a sustained relationship with a knowledgeable physician or treatment team, regardless of the severity of the brain damage. Therapy involves helping patients and their families be realistic about their losses and impairments, while encouraging hope and continued effort in rehabilitation. Helping patients and caregivers to interpret subtle and disruptive changes in personality in light of organic damage is particularly important to relieve guilt and blame.

• Psychological support

• Head injuries often precipitate an abrupt deterioration of general adaptation. Sudden adverse change inevitability produces anxiety, which may lead to demoralization or depression. In the case of head injury, damage to the brain impairs the person's ability to cope at a time when the need to adapt is greatest. The fact that patients with head injury are more distressed than those who experience equally disabling injuries to other parts of the body is not surprising.

• The meaning of any injury varies in part based on the patient's prior concerns and personality. For example, narcissistic patients feel narcissistically wounded by even minor losses of function. Prior emotional lability or capacity for aggression in a patient who is borderline may worsen following a head injury.

• Injury when a person is in transition or moving towards an important goal, such as marriage, school completion, or job performance, has a different meaning than injury occurring when someone feels stable, stagnant, or deteriorating. Injuries that occur on a job a person already dislikes or injuries that result from negligence may evoke resentment and feelings of entitlement that are absent in similar injuries in other circumstances.

• Understanding the person's preinjury personality, stresses, and the circumstances of the injury help establish realistic goals and minimize stress during rehabilitation and reentry into life. Interpreting the person's reactions to injury in light of his or her previous state builds trust, reflecting the degree to which the patient feels understood and accepted.

• Avoid interpreting changes in personality or behavior in light of developmental issues or conflicts without considering the impact of the injury itself. Such interpretations may produce confusion, guilt, unnecessary resentment, and fatalism. A present-oriented, problem-focussed therapy generally is best for patients after head injury, even those whose impairment appears to be driven by exaggerated emotional responses to the experience.

• Different stages of recovery require different types of psychological support. In the first months after injury, validating symptoms, helping patients relinquish responsibilities, mourning losses of function or hopes, and counseling patience with the pace of improvement are critical. Later, patients may need encouragement to push themselves to regain self-confidence and reassume their previous roles and responsibilities.

• Behavior modification
  • Research on patients who are severely impaired and who are treated in specialized units supports the value of behavior modification. Behavioral techniques may be used to discourage impulsivity, aggression, and socially inappropriate behavior. They also may encourage patients to be less apathetic or withdrawn. In any case, desired behaviors are reinforced with attention or specific rewards such as tokens for privileges. Undesirable behaviors provoke withdrawal of attention. Sometimes, specific techniques such as time-out or isolation from others may be used.

  • Teaching sleep hygiene is a behavioral intervention for insomnia. When effective, sedative medication may be used with caution in patients with head injury, due to their sensitivity to adverse effects.

  • Patients with simple PCS are not treated in hospital-based behavior programs, impeding research in this area. However, families can learn behavioral approaches that may benefit this group. Anxiety, loss of self-confidence, and intolerance of stimulation all seem ripe for behavioral interventions. While the line between impairment and exaggerated illness behavior is hard to draw, using concrete and immediate rewards to encourage the highest functioning of which patients seem capable is a sound therapeutic principle. Patients with head trauma are at risk of striking out at others. Family members, especially spouses, are often the victims of a patient's impulsivity, poor judgment, and impatience.

• Cognitive rehabilitation
  • Psychologists with special training typically conduct cognitive rehabilitation programs. The underlying principles are encouraging recovery in functions that are capable of improvement, compensation for areas of fixed deficit, and teaching substitute means of achieving particular ends. For example, gradually increasing time spent reading helps a patient both regain concentration and develop confidence in his or her ability to concentrate. Keeping lists allows a patient to compensate for decreased memory. Someone who has become dysarthric or aphasic may learn sign language as a substitute means of communication.

  • In general, cognitive rehabilitation is based on neuropsychological testing that clarifies deficits and suggests areas of preserved functioning in patients with dementia. Patient with PCS also have cognitive complaints, usually decreased attention and concentration. These symptoms may reflect slowly or partially reversible damage to white matter from DAI. Decreased attention and concentration seriously worsen anxiety and otherwise compromise patients' efforts to recover. When impaired concentration and attention are prominent in a patient with PCS, cognitive rehabilitation may be quite helpful.

• Family or network intervention

• The changes in personality, especially apathy, irritability, and aggression, in patients with head injury are especially burdensome to caregivers, family, or professional care providers. Head injuries cause more family distress than bodily injuries of equivalent severity. Counseling for caregivers is essential. When the patient is demented, interpreting impairments as organic and insisting on the legitimacy of the sick role are needed to relieve blame and guilt.

• Even when the caregiver understands the person's behavior is not within his or her control, the patient's slowness, inappropriateness, and erratic responsiveness can be exasperating or even frightening. Family members become isolated from usual support, especially when the person's impairments are severe, protracted, or fixed. Direct communication between the caregiver and the physician allows caregivers to vent their feelings and voice their concerns. Problem-solving interventions and referral to support groups for family members improve morale and enhance patient outcome. Regular staff or team meetings sustain morale in professional caregivers.

• Social services
  • Case management for patients with dementia sometimes is necessary to help patients apply for disability, locate specialized rehabilitation programs, attend to medical problems, and participate consistently in treatment.

  • When people have prominent severe problems of information procession or frontal lobe deficits manifested by impulsivity and poor judgment, they may be incompetent to make medical decisions or handle their own affairs. These 2 functions may differ. Guardianship, conservatorship, or some other protective legal arrangement may be needed. Physician evaluation typically is required, unless the person is competent enough to sign a power of attorney or designate a substitute payee.

• Medical support in legal proceedings

• Head injuries often occur in the context of car or workplace accidents, leading to legal proceedings for damages and compensation. The prognosis of mild or moderate dementia and PCS remain difficult to provide with certainty. Some patients recover fully from severe injuries with prolonged coma, others remain disabled for long periods after much milder insults. Moreover, involvement in legal proceedings seems to complicate recovery. Having to repeat the story of an injury to questioners, not knowing what expenses will be incurred and which will be covered by insurance, and proving the reality of subtle impairment without visible scars increase patients' stress and anxiety. Stress seems to slow or impede recovery by both psychological and physiological mechanisms. Malingering also may occur.

• Physicians caring for patients with head injuries should anticipate having to testify in depositions or court proceedings. They must clearly document impairment and objective findings, quantifying symptoms and progress in recovery whenever possible. Standard symptom rating scales, such as the symptom checklist 90 (SCL-90) or the Hamilton rating scales for anxiety and depression and the Positive and Negative Symptoms Scale may be used for appropriate patients. The Ranchos Los Amigos Cognitive Scale and the Neurobehavioral Rating Scale are especially sensitive to the particular symptoms of patients with head injury. Physicians should order neuropsychological testing to validate clinically suspected impairments that may be difficult to prove in face-to-face interaction.

• When called to testify, be aware of personal attitudes towards patients who are dependent, not improving quickly, not functioning to their ability, or expressing undesirable attitudes of resentment or entitlement. None of these factors should blind the physician to the reality of patients' distress and impairment. Testifying for either the defendant or the plaintiff in a head injury case requires honesty, humility, and awareness of the uncertainty surrounding the causes and the outcomes of the symptoms that patients develop.

	MEDICATION	Section 7 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Patients with head injury may require treatment with psychotropic medication for depression, mania, psychosis, aggression, irritability, emotional lability, insomnia, apathy, or impaired concentration. Headaches also may respond to psychopharmacologic treatment.

Brain damage renders patients more sensitive to adverse anticholinergic effects, seizures, and drug-induced parkinsonism. Doses in the usual therapeutic range may be needed to relieve target symptoms, especially for depression and mania; however, initiate at lower doses and titrate upward more slowly than in other patients under psychiatric care.

Dopamine-blocking agents (eg, haloperidol) and adrenergic-blocking agents (eg, clonidine, prazosin) compromise brain tissue repair in animal laboratory models. Dopamine-potentiating agents (eg, dextroamphetamine) enhance recovery in animal models. These effects have not been documented in humans with head injury, although alpha-blockers, haloperidol, and benzodiazepines may adversely affect functional outcome after strokes. According to a recent FDA advisory, atypical antipsychotic drugs of various classes (including aripiprazole, risperidone, quetiapine, olanzapine) increase mortality when given for behavioral disorders in patients who are elderly and demented. The implication of these findings for the treatment of dementia or behavioral disorders after head injury are unknown. In the studies cited by the FDA, the excess mortality reflected deaths from infections and heart disease, conditions more common in the elderly population of patients than in the younger population of patients with head injury.

Practitioners should be aware, at minimum, that the use of antipsychotic drugs for conditions other than schizophrenia and mania is off-label and should be carefully monitored.

Drug treatments for patients with brain injury are extrapolated from studies of patients after stroke or other types of brain damage. These patients may not be comparable to patients with head injuries, especially those with DAI. Clinical trials in patients with head injury typically are small. No broad consensus or established guidelines exist regarding psychotropic drug treatment after head injury.

Specific target symptoms and appropriate medications include the following:

• Depression - Selective serotonin reuptake inhibitors (SSRIs), nefazodone, bupropion, nortriptyline

• Insomnia - Trazodone, mirtazapine

• Mania - Valproic acid, carbamazepine, lithium

• Emotional lability (eg, pathological laughing, crying) - Bromocriptine, nortriptyline, fluoxetine

• Psychosis - Olanzapine, quetiapine, aripiprazole, ziprasidone, risperidone, haloperidol

• Hypoarousal - Dextroamphetamine, methylphenidate

• Poor concentration (eg, apathy, fatigue) - Methylphenidate, bromocriptine, amantadine, levodopa and carbidopa (improvement may not be sustained)

• Chronic aggression and irritability - Antiepileptic drugs, SSRIs, olanzapine

• Headaches - Amitriptyline, nonsteroidal anti-inflammatory drugs (NSAIDs), antimigraine drugs

• Anxiety - Buspirone

Acute agitation or aggression may be treated with benzodiazepines; however, first-line treatment of chronic symptoms includes drugs having less sedative effects or impact on cognition. Avoid phenobarbital for treating seizures due to sedation. Over-the-counter anticholinergic hypnotics are not to be used for patients with head injury.

Drug Category: Antidepressants -- Treatment of depressive syndromes due to traumatic brain injury. Indications include signs and symptoms of major depression with or without psychosis, dysthymia, or adjustment disorder.

SSRIs are the antidepressants of choice due to minimal anticholinergic effects. All are equally efficacious. The choice depends on adverse effects and drug interactions. SSRIs also are used to treat behavioral disturbances resulting from head trauma.

Tricyclic antidepressants (TCAs) are used when unable to use SSRIs. Their unfavorable adverse effect profile prompted development of newer antidepressants. Advantages include ability to obtain blood levels, thus ensuring therapeutic response and avoiding toxicity. Prior to initiating, obtain ECG and blood pressure.

Newer antidepressants useful for sleep disturbances include trazodone and mirtazapine. They are structurally unrelated to TCAs, tetracyclics, or MAOIs. Cardiac conduction effects of trazodone are qualitatively dissimilar and quantitatively less pronounced than TCAs and therefore are less toxic in overdose.

Drug Name	Fluoxetine (Prozac) -- Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine.
Adult Dose	10 mg/d PO every am; increase after several wk to 20 mg/d; may increase further as tolerated; not to exceed 80 mg/d
Pediatric Dose	<18 years: Not established >18 years: Administer as in adults
Contraindications	Documented hypersensitivity; MAOIs
Interactions	Inhibits CYP3A4; thus, increases toxicity of isoenzyme substrates (eg, diazepam, trazodone, TCAs) by decreasing clearance; increases toxicity of MAOIs, wait at least 10 d after discontinuing MAOIs to initiate fluoxetine, wait at least 5 wk after discontinuing fluoxetine to initiate MAOIs; may displace highly protein-bound drugs (eg, warfarin); serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) may occur when coadministered with full doses of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan); however, cautious use of small doses of agents such as trazodone for sleep or buspirone for anxiety may be effective; close monitoring for emergence of serotonergic adverse effects is warranted
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hepatic impairment (adjust dose) and history of seizures; common adverse effects include headache, somnolence, nervousness, dizziness, nausea, diarrhea, xerostomia, general weakness, and sexual dysfunction; symptoms of weakness, lethargy, headache, anorexia, weight gain, confusion, or constipation may indicate hyponatremia

Drug Name	Citalopram (Celexa) -- Enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. No head-to-head comparisons of SSRIs exist, although, based on metabolism and adverse effects, citalopram is considered SSRI of choice for patients with head injury.
Adult Dose	20-60 mg PO qd; 10 mg/d initially, titrate by 10 mg/wk
Pediatric Dose	Not established; child psychiatrists treating patients with head injury recommend starting with half the usual adult dose when using drugs for which pediatric dosages have not been established
Contraindications	Documented hypersensitivity, concurrent MAOI therapy
Interactions	Serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan), discontinue other serotonergic agents at least 2 wk prior to SSRIs; low doses of SSRIs and buspirone or trazodone may be combined if carefully monitored; may be potentiated by azole antifungals, omeprazole, and macrolides
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in cirrhosis (adjust dose), suicidal tendencies, SIADH, DM, seizure disorders, orthostasis, and breastfeeding; common adverse effects include fatigue, GI toxicity, and sexual dysfunction

Drug Name	Amitriptyline (Elavil) -- Tricyclic tertiary amine. Inhibits neuronal reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in the CNS. Highly anticholinergic, although considered one of the best-studied antidepressants. Use for chronic pain, including headache. Doses for chronic pain are one-half to one-third of those for depression.
Adult Dose	10-25 mg PO hs initially; may increase gradually to desired effect; not to exceed blood level >150 ng/mL
Pediatric Dose	Children: 0.05 mg/kg PO hs initially, gradually increase over 2-3 wk to 0.25-1 mg/kg PO hs Adolescents: 3-5 mg/kg PO hs initially, gradually increase to 10 mg PO tid
Contraindications	Documented hypersensitivity; concurrent MAOI or use within 14 d of MAOI; do not use during acute recovery phase of MI
Interactions	Phenobarbital may decrease effects; coadministration with CYP2D6, CYP3A4, or CYP2C9 inhibitors may increase amitriptyline levels; additive effect with drugs prolonging QT interval (eg, sotalol, amiodarone, gatifloxacin); inhibits hypotensive effects of guanethidine; increases toxicity of alcohol, disulfiram, and warfarin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use nortriptyline (amitriptyline active metabolite) if anticholinergic effects intolerable; cautious use in seizures, suicidal ideation, arrhythmias, orthostasis, angle-closure glaucoma, urinary retention, hepatic dysfunction (adjust dose), or hyperthyroidism

Drug Name	Nefazodone (Serzone) -- 5-HT2–receptor antagonist and inhibits the reuptake of 5-HT. Negligible affinity for cholinergic and histaminergic receptors. Does not suppress REM activity, unlike other antidepressants. Decreases light-stage sleep and frequency of awakenings.
Adult Dose	50 mg PO bid initially, gradually increase at weekly intervals to 200-500 mg/d PO divided bid; not to exceed 600 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, MAOI within 14 d of initiating treatment; concurrent administration with pimozide
Interactions	Inhibits CYP3A4, thus increasing serum levels of substrates (eg, carbamazepine, cyclosporine, triazolam); increased risk of serotonin syndrome with other serotonergic drugs (eg, SSRIs, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan); decreases effect of anticoagulants, oral hypoglycemics, diuretics, clonidine, and methyldopa; increased toxic effects of digoxin and MAOIs; increased risk of myopathy and rhabdomyolysis with HMG Co-A inhibitors (eg, pravastatin, simvastatin); may enhance response to alcohol, barbiturates, and other CNS depressants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in preexisting cardiac disease, hepatic dysfunction (adjust dose), initial recovery phase of MI, and priapism; common adverse effects include hypotension (including orthostatic hypotension and syncope), drowsiness, dizziness, or blurred vision; caution patient regarding tasks requiring alertness, coordination, or dexterity

Drug Name	Trazodone (Desyrel) -- 5-HT2–receptor antagonist that inhibits reuptake of 5-HT. Negligible affinity for cholinergic, adrenergic, dopaminergic, or histaminic receptors. Good hypnotic properties. Effective in reducing agitation in patients with head trauma or dementia.
Adult Dose	25-50 mg PO hs initially, gradually increase by 50 mg/d q3-7d to sedating effect; not to exceed 400 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May enhance response to alcohol, barbiturates, and other CNS depressants; may increase digoxin and phenytoin serum levels; may decrease hypoprothrombinemic effects of Coumadin; increased risk of serotonin syndrome with other serotonergic drugs (eg, SSRIs, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan); may increase hypotensive effects of antipsychotics; drugs inhibiting CYP2D6 (eg, fluoxetine) may decrease trazodone metabolism
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in preexisting cardiac disease, initial recovery phase of MI, and priapism; common adverse effects include hypotension (including orthostatic hypotension and syncope), drowsiness, dizziness, or blurred vision; caution patient regarding tasks requiring alertness, coordination, or dexterity

Drug Category: Dopaminergic agents -- Enhancing dopamine function may improve concentration, attention, and interest in patients after head injury. Dopaminergic drugs include bromocriptine, amantadine, and levodopa/carbidopa. Animal studies demonstrate that dopamine function enhancement may have neuroprotective effects. Bromocriptine combined with antidepressants has been used for pathological emotional lability. The most potent dopaminergic drug is levodopa; therefore, it also produces the highest toxicity (see Parkinson Disease Dementia). Other drugs should be tried first. Stimulants (eg, dextroamphetamine, methylphenidate) also enhance dopamine function. Stimulants and direct or indirect dopamine agonists affect dopamine pathways differently, despite similar mechanisms of action.

Drug Name	Bromocriptine (Parlodel) -- Semisynthetic ergot alkaloid derivative. Strong dopamine D2-receptor agonist. Partial dopamine D1-receptor agonist.
Adult Dose	1.25 mg (one-half of 2.5-mg tab) PO pc bid, increase by 2.5 mg/d q2-4wk prn; usual dosing range is 10-40 mg/d; not to exceed 100 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, severe ischemic heart disease, severe peripheral vascular disorders
Interactions	Additive toxicity may increase with ergot alkaloids, amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine; antipsychotics may decrease effect; sympathomimetics and erythromycin may increase effect
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause hypotension, CNS toxicity, GI toxicity, or leg cramps; caution in hepatic disease (adjust dose) and breastfeeding

Drug Name	Dextroamphetamine (Dexedrine) -- Increases circulating dopamine and norepinephrine in cerebral cortex by blocking reuptake of norepinephrine or dopamine from synapse.
Adult Dose	5-30 mg/d PO 30-60 min ac in divided doses
Pediatric Dose	<3 years: Not established 3-5 years: 2.5 mg PO every am initially, increase by 2.5 mg/d qwk to response >5 years: 5 mg qd or bid, increase by 5 mg/d qwk to response; not to exceed 40 mg/d
Contraindications	Documented hypersensitivity, hypertension, MAOIs used within 14 d, advanced arteriosclerosis, hyperthyroidism, glaucoma, diabetes mellitus, hyperthyroidism
Interactions	Coadministration with MAOIs may precipitate hypertensive crisis; coadministration with anesthetics may precipitate arrhythmias; may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and norepinephrine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in angina, glaucoma, cardiovascular disease, and psychopathic personalities; may worsen Tourette syndrome or other disorders with motor tics

Drug Category: Antipsychotic agents -- Treatment of hallucinations, ideas of reference, delusional preoccupation, and agitation. Older antipsychotics with strong anticholinergic adverse effects (eg, chlorpromazine, thioridazine) may worsen cognitive function. Potent conventional antipsychotics (eg, haloperidol) have been used in patients with dementia with psychotic symptoms. While these drugs are effective, patients with brain damage are more susceptible to drug-induced parkinsonism. Haloperidol produces high levels of parkinsonian symptoms and risk of irreversible syndrome of tardive dyskinesia.

New antipsychotic drugs (eg, risperidone, olanzapine) may have particular efficacy in treating agitation and psychosis in patients with Alzheimer disease and for cognitive symptoms in schizophrenia. However, these drugs, along with atypical antipsychotic drugs of other classes (eg, aripiprazole, quetiapine) may also increase mortality from infection and heart attacks in older patients with dementia. Taken together, these findings suggest that patients with head injuries may benefit from these drugs, but they should be used with caution and carefully monitored. The adverse effects of somnolence, dizziness, and unsteady gait are of particular concern in patients with head injury. The known potential of many antipsychotic drugs to cause hyperglycemia, weight gain, and type 2 diabetes mellitus is of concern in every patient group.

The atypical antipsychotic drugs olanzapine and ziprasidone are available to be administered parenterally, as may occasionally be needed in an emergency to control agitation or when patients have met local legal standards for the involuntary use of psychotropic medication. Behavioral interventions, such as controlling stimulation or engaging the patient verbally, may allow for the voluntary use of oral medication, which is preferable in all but the most imminently dangerous situations.

Drug Name	Risperidone (Risperdal) -- Binds to dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor. Improves negative symptoms of psychoses and lowers incidence of extrapyramidal adverse effects.
Adult Dose	0.5 mg PO qd initially, gradually increase to optimum range of 4-8 mg/d; not to exceed 10 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Carbamazepine may decrease serum levels; clozapine may increase serum levels; may antagonize levodopa effects
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause extrapyramidal reactions (especially >6 mg/d); hypotension/orthostasis, tachycardia, arrhythmias, amenorrhea, galactorrhea, sexual dysfunction, GI toxicity, cholestatic jaundice

Drug Name	Quetiapine (Seroquel) -- May act by antagonizing dopamine and serotonin effects.
Adult Dose	25 mg bid/tid initially, gradually increase (patients with head injury require a slower upward titration than usually is recommended) to 300-400 mg/d divided bid/tid; not to exceed 750 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May antagonize levodopa and dopamine agonists; CYP3A4 inducers (eg, phenytoin, thioridazine) may reduce levels; CYP3A4 inhibitors (eg, itraconazole, erythromycin) may increase levels; may decrease warfarin clearance, monitor aPTT
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May induce orthostatic hypotension associated with dizziness, tachycardia, and syncope; neuroleptic malignant syndrome has been reported; caution with seizures, cerebrovascular disease, and hepatic dysfunction (adjust dose); common adverse effects include somnolence, agitation, headache, and dizziness

Drug Category: Antiepileptic drugs -- Behavioral disturbances (eg, chronic aggression, agitation) are severe complications of head injury. Pharmacological agents used to treat these behaviors include antiepileptic drugs, SSRIs, and beta-blockers.

Drug Name	Carbamazepine (Tegretol) -- Originally indicated for the treatment of epilepsy involving the temporal lobes. Became known as a mood stabilizer in 1970s when Japanese researchers found it to be helpful in patients with bipolar disease who were refractory to lithium. Used for reducing frequency and severity of manic and depressive components of bipolar disorder. Not considered first-line treatment. Used to stabilize episodic aggressive behavior. Double-blind studies have demonstrated moderate effect in decreasing aggressive behavior in patients with dementia and those with impulse control disorders. Case studies describe effect in patients with seizures or previous head injury. Serum levels of 8-12 mcg/mL may lessen impulsivity, irritability, and hostility in patients with cognitive disorders.
Adult Dose	IR: 50-100 mg PO tid initially, gradually titrate to response by 200 mg/d qwk to 300 mg PO qid; not to exceed blood level >12 mcg/mL ER: Total daily dose divided bid
Pediatric Dose	50 mg PO bid (suspension: 25 mg PO qid) initially; gradually increase qwk by 50 mg/d until desired effect; not to exceed blood levels >12 mcg/mL
Contraindications	Documented hypersensitivity, history of bone marrow depression, administration of MAOIs within last 14 d
Interactions	Induces its own metabolism; therefore, half-life declines over 1 mo from 36 h to 10-20 h, adjust dose accordingly; serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister within 14 d of MAOIs; cimetidine may increase toxicity, especially within first 4 wk of therapy; may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels)
Pregnancy	D - Unsafe in pregnancy
Precautions	Cross-sensitivity with TCAs; obtain CBCs, LFTs, and serum iron prior to treatment, during the first 2 mo, and yearly thereafter; monitor low-normal or below normal WBC counts and neutrophil counts q2wk for the first 3 mo; thereafter, individualize monitoring based on previous results, discontinue if WBC <3000/mm3 or neutrophils <1000/mm3; recommend target blood levels of 4-8 mcg/mL in patients with head injury; caution with increased intraocular pressure; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness; other adverse effects include Stevens-Johnson syndrome, hepatitis, nausea, ataxia, and pancreatitis

Drug Name	Valproic acid (Depacon, Depakene, Depakote) -- Mechanism of action is not established, although activity may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. May potentiate postsynaptic GABA responses, affect potassium channel, or have a direct membrane-stabilizing effect. Anticonvulsant used for mood stabilization in patients with head injury. Used in treatment of bipolar disorder. Effective in management of agitation and aggression in patients with dementia. Specific therapeutic range has not been defined for management of aggression. Available in capsules, tablets, syrup, and sprinkles.
Adult Dose	125 mg PO tid initially; not to exceed blood level >100 mcg/mL; lower doses required compared to treatment of mania or seizures
Pediatric Dose	5-10 mg/kg/d initially, gradually titrate to response; not to exceed blood level >100 mcg/mL
Contraindications	Documented hypersensitivity, hepatic disease
Interactions	Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations; valproate may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in patients who are HIV seropositive
Pregnancy	D - Unsafe in pregnancy
Precautions	Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or a hemostasis/coagulation disorder occurs; hyperammonemia may occur, resulting in hepatotoxicity Use in patients receiving multiple drugs increases risk of hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness; caution in renal disease, Addison disease, blood dyscrasias, and organic brain disease; monitor LFTs and serum level; children may be more vulnerable to hepatotoxicity; divalproex sodium form of valproic acid (Depakote) may improve GI tolerability; fatal pancreatitis has been reported, check amylase/lipase and discontinue medication if patient develops symptoms of pancreatitis

Drug Category: Mood stabilizers -- The mood stabilizer that is not an anticonvulsant is lithium. Studies have demonstrated potential benefit of lithium for explosive and violent behavior in patients with organic disorders. Double-blind placebo-controlled trials conducted over 16 wk on violent adult prisoners, patients with mental retardation, and patients with brain injury demonstrated decreased impulsivity and aggressive behavior. Lithium levels during the trials were maintained at 0.7-1.0 mEq/L.

Drug Name	Lithium (Eskalith, Lithane, Lithobid, Lithotabs) -- Primarily used for acute manic episodes and depression of bipolar disorder and unipolar depression. Also used to treat agitation and violence. Alters sodium transport in nerve and muscle cells, resulting in intraneuronal metabolism of catecholamines; however, specific mechanism of action is unknown.
Adult Dose	IR: 150 mg PO tid initially, titrate to maintain serum level of 0.5-1 mEq/L ER: Total daily dose divided bid
Pediatric Dose	6-12 years: 7.5-30 mg/kg/d PO divided tid/qid; not to exceed usual adult dose; adjust dose according to serum levels
Contraindications	Documented hypersensitivity; renal impairment; patients with severe cardiovascular disease should be placed on alternate mood stabilizer because lithium may worsen arrhythmias in patients with sinus node dysfunction
Interactions	Medications that increase levels include thiazide diuretics, NSAIDs, erythromycin, metronidazole, spironolactone, triamterene, enalapril, and tetracycline; medications that decrease levels include acetazolamide and aminophylline; medications that have increased toxicity when administered concurrently with lithium include haloperidol, succinylcholine, digoxin, alpha-methyldopa, and calcium channel blockers
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in sodium depletion, thyroid insufficiency, dehydration, diabetes, and infection; reduce dose in elderly patients or in cases of renal dysfunction; monitor lithium levels and renal function; common adverse effects include tremor, polyuria, and polydipsia; signs and symptoms of toxicity may occur at lower serum levels among patients with head injury; toxicity includes mental confusion, nausea/vomiting, diarrhea, tremor, goiter, polyuria, and flattened or inverted T waves on ECG; may cause reversible real or subclinical hypothyroidism or hyperparathyroidism, monitor TSH and calcium levels

Drug Category: Benzodiazepines -- Used for rapid control of agitation in dementia. They potentially worsen cognition; thus, their use in correcting sleep-wake cycle disturbances or treating anxiety in this population is discouraged. Used primarily to produce rapid calming needed for patients who are violent or agitated.

Drug Name	Lorazepam (Ativan) -- DOC for acute agitation in dementia. Short duration and less accumulation with repeated doses.
Adult Dose	1-2 mg/dose PO/IM initially; may repeat q1h prn; alternatively, 1-2 mg/dose IV; not to exceed administration rate of 2 mg/min; may repeat q30min prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, preexisting CNS depression, hypotension, narrow-angle glaucoma
Interactions	Toxicity of benzodiazepines increases when used concurrently with MAOIs, alcohol, phenothiazines, and barbiturates
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in hepatic or renal impairment (adjust dose), dehydration, myasthenia gravis, organic brain disease, and Parkinson disease

Drug Category: Beta-blockers -- Effective for treating aggression resulting from head injury. They also are used for reducing restlessness and disinhibition. Treatment for persistent agitation and aggression in organic brain syndromes.

Drug Name	Propranolol (Inderal) -- Nonselective beta-adrenergic receptor antagonist. Widely studied for its therapeutic effects on agitation due to organic brain syndrome. Therapeutic effect may be observed within 2-4 wk, improvement within 8 wk.
Adult Dose	20 mg PO tid initially; if hypotensive or bradycardic, initiate at 20 mg PO qd; gradually increase by 60 mg/d q3d as tolerated until symptoms controlled
Pediatric Dose	0.5 mg/kg/d PO divided q12h, gradually titrate as tolerated to 1-2 mg/kg/d divided q12h
Contraindications	Documented hypersensitivity, uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities, Raynaud syndrome, severe reactive airway conditions (eg, asthma, emphysema)
Interactions	Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines (eg, thioridazine) may increase
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may mask signs of acute hypoglycemia and hyperthyroidism; may exacerbate asthma/COPD; caution in angina, CHF, or asthma; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor BP and pulse during dose titration; drug requires gradual discontinuation

Drug Category: Atypical antipsychotics -- See above.

Drug Name	Olanzapine -- May inhibit serotonin, muscarinic, and dopamine effects.
Adult Dose	5 mg PO initially, increase as tolerated, not to exceed 10 mg Higher doses, while sometimes needed for the treatment of psychosis, have not been more effective than placebo in demented patients with Alzheimer disease
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Fluvoxamine may increase effects; antihypertensives may increase risk of hypotension and orthostatic hypotension; levodopa, pergolide, bromocriptine, charcoal, carbamazepine, omeprazole, rifampin, and cigarette smoking may decrease effects
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in narrow-angle glaucoma, cardiovascular disease, cerebrovascular disease, prostatic hypertrophy, seizure disorders, hypovolemia, and dehydration

	FOLLOW-UP	Section 8 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Deterrence/Prevention:

• Primary prevention of head injury involves the use of protective gear in contact sports, seat belts, bicycle and motorcycle helmets, and hard hats in appropriate jobs.

• For elderly patients, altering the environment to minimize the risk of falls is important.

• Protecting children from child abuse helps prevent head injuries.

• Patients who have had one head injury are at risk for others.

• Identification and treatment of substance abuse makes subsequent injury less likely.

• Some patients with head injury are parasuicidal. They may benefit from treatment of depression, character disorders, and other conditions associated with suicide.

• Restricting return to play for athletes prevents SIS.

• Prevention of sequelae in patients once they have been injured is an active area of research. Recent reviews of the subject suggest hypothermia during the period of coma may mitigate tissue damage. Prophylactic use of anticonvulsants is not recommended.

Complications:

• Reactions to anticholinergic, analeptic, and parkinsonian adverse effects of medication

• Subdural and epidural hematomas

• Hydrocephalus

• Partial complex or grand mal seizures

• Exacerbations of preexisting psychiatric disorders, including preexisting dementia

• Conversion symptoms

• Conversion symptoms typically occur when a person feels trapped in a threatening situation, especially if he or she is unable to openly talk about the dilemma with others who are trusted.

• Patients with head injury often face such dilemmas, being forced to return to work when they feel unable, being expected to perform normal family roles despite significant problems of cognition or mood, and being subject to hostile legal scrutiny. Moreover, the head is a symbolically significant part of the body. For all of these reasons, some of the nonspecific distress of patients with head injury and, more rarely, some of their focal complaints may be understood as conversion symptoms or somatization.

Prognosis:

• The prognosis of mild or moderate dementia and PCS remains difficult to provide with certainty. Some patients recover fully from severe injuries with prolonged coma; others remain disabled for long periods after much milder insults.

Patient Education:

• Patients with dementia

• These patients need simple explanations of their impairments. While they may be aware of cognitive dysfunction, they may lack insight into impairments in judgment, changes in personality, elevated mood, or paranoid symptoms. Education should include the expected course of improvement, with the greatest improvement expected in the first 6 months but delayed improvement possible as long as 5 years after injury.

• Caretakers of patients with dementia need a great deal of ongoing education and support. Importantly, the patient's environment must be neither tedious nor overstimulating. Maintaining consistent routines of light and dark, eating, sleeping or lying in bed, performing bathroom activities, and participating in therapeutic or recreational activities help patients remain emotionally balanced and minimize caregiver burden.

• Keeping the environment safe by eliminating area rugs to reduce falls, providing tub bars, and putting child locks on cabinets or stove knobs also is important in the care of patients with dementia. If the patient is capable of going out alone, the caregiver should ensure that he or she knows the routes well, carries identification, wears a medic alert bracelet, and knows how to use phones (especially cell phones) and busses.

• Caregivers for patients with mild dementia need to decide whether the person should continue to have access to checking accounts or credit cards. If the person is willing and competent, the caretaker should consider getting power of attorney, in order to monitor the person's use of financial resources. If the patient has markedly poor judgment or seems seriously incompetent, the caregiver should seek formal conservatorship, to have legal authority to manage the person's resources.

• Caregivers should be included in the patient's relationship with health care professionals. They should be specifically told to seek help if the patient has very disrupted sleep; does not eat a balanced diet; or is incontinent, aggressive, or sexually inappropriate. Any marked change in behavior should prompt a call to the clinician. Because patients with dementia do not always show typical symptoms when acutely ill, taking the patient's temperature and looking for signs of infection is a particularly important step if the patient shows a change.

• Clinicians, in turn, must be accessible to caregivers. Meeting with more than one family member to stress the importance of having family members and friends share the burdens of providing care often is an overlooked step. Although one particular friend or relative may know the most about a patient and assume most of the responsibility, sharing this with others reduces the likelihood of the caregiver becoming isolated or depressed, an otherwise common outcome of providing long-term family care.

• Patients with postconcussional syndrome

• Patients with PCS need to know that headaches, dizziness, fatigue, irritability, poor concentration, and decreased memory are common in the first 3-6 months after injury. These symptoms fully resolve in most patients after mild injury. However, persistent impairment is possible. Patients should know that anxiety, depression, decreased concentration, and other persistent symptoms may improve with rehabilitation, psychological support, and medication.

• Caregivers need to adopt a posture of encouragement and expectation that the patient will try to be as independent and productive as possible. At the same time, caregivers need to be patient and tolerant. They should accept that the patient may have real limitations and that these will likely worsen if the person is tired, ill, or acutely stressed. Emphasizing what the person can still do, rather than what seems to be lost, generally is helpful.

• The traumatic brain injury page of the National Institutes of Health contains links to other organizations providing education and support (see National Institute o