Initial treatment of suboptimal arousal, attention, or initiation requires medical investigation for occult electrolyte dyshomeostasis, hypoglycemia, hypovolemia, anemia, infection, evolving stroke, seizures,... Dilantin toxicity secondary to drug interactions has been identified as an insidious cause of vegetative depression.(24) Hyponatremia occurs in up to one-third of patients following severe TBI, and patient's with sodium levels less than 128 mEq/L may exhibit impaired cognition.(53) The danger of missing occult pathology in early, readily treatable stages cannot be overemphasized. A sudden decline or plateau in neurologic recovery in a stroke or TBI patient may alert the clinician to consider hydrocephalus, subdural hematoma, intracranial abscess, meningitis, and additional medical conditions.
Caloric, mineral, fluid, and protein malnutrition will negatively impact cognition. Folate, thiamine, and other vitamins are requisite to cortical processing, and may require supplementation. Body weights, pre-albumin levels, hemoglobin levels, vitamin levels, and calorie counts require monitoring and may suggest the indication for gastrostomy placement.
Sensory function must be maximized. If visual acuity and audition are at optimal capacity, then already variably compromised cognitive status will be less burdened, and less likely to contribute to impaired attention. External auditory canals should be assessed for middle ear infections, cerumen impaction,... Cataracts, glaucoma, and other causes of impaired visual acuity must be addressed. A low threshhold should be assumed to consult ophthalmology, ENT, and audiology, especially if comorbid aphasia is present.
Sensory overstimulation should be minimized to maximize attention capacity as complex information processing is often deficient. In contra-distinction to awakening the comatose or reversing the vegetative state, patients should be placed in quiet, single rooms, not in the hallway or near a busy nursing station. The patient should not be fully isolated, as inadequate sensory stimulation may impair arousal. Lights should be neither too bright nor too dim. If lights are too dim then patients with impaired attention may misinterpret dimly lit objects and respond to these illusions. As cognition improves, meals with other patients should occur in a central, monitored dining area to facilitate social integration. Home visits on weekends and frequent family visits further enhances socialization.
Frustration can be diminished by facilitating communication. Word boards, gestures, and simple yes/no finger movements, head nods, and eye blinks can greatly diminish frustration in aphasic patients.
Re-establishment of regular sleep-wake cycles to maximize a full night's sleep will promote alertness and improved attention. Delivery of medications and vital sign assessment should be scheduled such that the frequency of awakenings is minimized. Scheduled daytime naps may be required, but excessive daytime sleep may reduce the patient's ability to sleep at night. Caffeine and psychostimulants should not be given after noontime.
A predictable schedule should be established with consistent times of wakening, meals, therapies, bathing, dressing, naps, bedtime,... This will help the patient differentiate from his internal and external environments.
Orientation will be enhanced with a clock and calendar in the patient's room as well as a daily schedule chart. If placed on a large chart on the wall in his room, he can frequently refer to it. This will also generate feelings of stability as he senses that his environment is well ordered. Placing family pictures and familiar personal belongings (blankets, pillows, stuffed animals, posters,...) in his room will also contribute to security, as will visits from friends and family. Attempt to have the same nurse care for the patient to establish continuity and familiarity for the patient.
Avoid complex, stressful activities to which the disinhibited patient may combatively respond. Explain activites slowly and answer questions before asking the patient to attempt them. Attempt to simplify tasks or break complex tasks into less challenging subcomponents. Performance will be enhanced if psychologic demands are limited. Patients may be more likely to participate in PT and OT if family is present and encouraging.
Neuropsychologists can be fundamental to construct behavior programs which may enhance cognition.(16) For example, positive reinforcement through liberal praise, rewards with cookies after staying awake for an entire therapy session will increase the frequency of cooperative behavior with therapists and nurses.
When chemical restraints are used, the smallest dose necessary should be selected. Potent chemical restraints include antipsychotic/neuroleptics and benzodiazepines. Neuroleptics are grossly overutilized in the management of disruptive behavior. They globally suppress all aspects of cognition, including new learning.(38,39) They can cause anhedonia, akathisia, irreversible tardive dyskinesia, parkinsonian symptoms, dystonia, neuroleptic malignant syndrome, cholestatic jaundice, depression, apathy, motor dyscoordination, attention deficits, emotional dyscontrol,(4) and memory impairment.(55)
Long term utility of neuroleptics is best reserved for patients with true psychotic thought process disorders. Psychosis which may accompany acute TBI or acute delirium in a demented patient often resolves after only a few days of neuroleptics, and chronic treatment is often not necessary. A trial taper of antipsychotics is indicated.
If the goal is the control of delusions and/or hallucinations, Haldol is a superior agent since it is far less sedating at equipotent doses relative to most other antipsychotics. Haldol has a lower risk of epileptogenic activity and less cardiopulmonary suppression than phenothiazines. If sedation is the goal, however, then phenothiazines are better than haloperidol as the former class of antipsychotics has less risks for tardive dyskinesia at equipotent sedative doses. Newer antipsychotics with less extrapyramidal side effects are generally preferred to the older less receptor specific classes of neuroleptics.
Benzodiazepines have profound side effects in terms of impairing new learning via the anticholinergic properties of this class. In addition, benzodiazepines not uncommonly result in rebound mood depression, anxiety disorder, and insomnia. Though successfully marketed as being different from all other benzodiazepines, clonazepam has similar untoward risks and should be considered contra-indicated in the vast majority of patients.
Clinicians are encouraged to employ behavioral techniques to treat disinhibited behavior and not benzodiazepines or neuroleptics as they may cause paradoxical disinhibition when the drug eventually is cleared, and sedation when the agent is bioactive. This is particularly important when these drugs are ordered as "prn" and nursing staff unfamiliar with the patient or overly responsive to behavior which neither threatens the safety of the patient or others.
TREATMENT - NONPHARMACEUTICAL
If shunt malfunction is suspected, then lumbar puncture can be attempted to produce regression of akinetic mutism or other states of impaired AAI.(163) Mechanical reversible extrinsic compression of fundamental tracts must be excluded prior to pharmaceutical augmentation of dopaminergic or noradrenergic projections.
Neuropsychologists and occupational and speech therapists can train patients to use internal cueing systems to enhance AAI. Patients can be taught to repeatedly ask themselves if they are sufficiently aroused or attentive, and compel themselves to become more so. Similarly, they can ask themselves if they are initiating sufficient conversation during a social encounter, and subsequently assume corrective action. Successfully employed compensatory strategies include self-cueing, and self-monitoring.(116)
TREATMENT - DRUG SUBSTITUTION/TAPER
A significant number of medications have been identified which adversely affect cognition. The clinician must initially assess if the pharmaceutical is even necessary. If the drug is required then assessment without delay must commence to determine if a less cognitively detrimental medication can be substituted to achieve identical efficacy.
Haloperidol, a dopamine receptor blocking agent, has been known for many years to delay the rate of motor recovery after cortical injuries.(38) Neuroleptics impair attention, memory, and other aspects of cognition.(44) Antipsychotics are also proconvulsant,(105) and cause akathisia and predispose to behavioral disinhibition. Akathisia is a cognitive and motor restlessness that greatly impairs capacity to maximally utilize attention faculties. It is also extremely distressing to the patient and may result in attempted suicide.(138) Though usually dose and duration dependent, a single dose of neuroleptics may precipitate irreversible tardive dyskinesia.(108) In addition, dopamine antagonists may induce fatal neuroleptic malignant syndrome and torsade de pointes ventricular dysrhythmia.(6,40,94,113) Torsade may not universally be predicted by a prolonged QT interval.(40) The clinician must simultaneously recall that neuroleptics can enormously enhance quality of life in people with premorbid psychotic thought processing disorders such as schizophrenia.
Clonidine and prazosin have been identified as agents which retard motor recovery because of their alpha-adrenergic antagonism,(15) and consideration for substitution for less cognitively offensive antihypertensives such as ACE inhibitors or calcium channel blockers should be pursued.
Spasticity is a common sequelae of acquired brain injury. Phenol or botulinum toxin injections are entirely bereft of cognitive side effects, and control spastic hypertonus quite effectively. If the principal manifestation of the triad of spasticity is that of mass spasms, then a systemically active agent may be more efficacious as a conservative intervention to ameliorate symptoms. Dantrolene is felt to be least cognitively offensive, but dose and duration dependent hepatotoxicity may preclude delivery to young patients. Baclofen in low doses is often well tolerated, especially if restricted to nocturnal dosing. Valium and other benzodiazepines have significant central nervous system toxicity, and baclofen intrathecal pump implantation should be considered before prescription of Valium is entertained.
In the treatment of gastritis, famotidine (Pepcid) may have less cognitive depression than ranitidine (Zantac) which may have less CNS depression than cimetidine (Tagamet).(37) Carafate and antacids are drugs that have far less CNS effects than H2 receptor blockers. Proton pump inhibitors are far more desirable with respect to cognitive side effects, and newer agents have less drug-drug interactions.
In the treatment of mood depression, potent anticholinergic medications can impair memory and be sedating, contributing to confusion. Neuroleptics, benzodiazepines, and some antidepressants have potent anticholinergic effects. Serotonergic, dopaminergic, and MAO inhibitor antidepressants are alternatives to treat mood depression. Trazodone may cause daytime sedation,(4) and substitution or earlier ingestion may be required. Trazodone is relatively contra-indicated in males given the risks for priapism and emergent surgical decompression.
Benzodiazepines are sedating and impair AAI as well as memory. Chronic use of benzodiazepines results in aggressiveness, anxiety, mood depression, and additional cognitive deficits. If anxiety is the indication for treatment with benzodiazepines, then serotonergic and GABA-ergic medications are more desirable alternatives.
Buspirone (BuSpar) is a serotonin 1A receptor modulator. It does not impair memory,(74) unlike benzodiazepines. Also unlike benzodiazepines, it does not cause dependence or withdrawal symptoms.(77) Potential uncommon side effects include dizziness, nausea, headache, and nervousness. Dosing is 5 mg po TID - 20 mg TID.
For treatment of nausea, the antipsychotic derived metoclopramide (Reglan) and Compazine can suppress cognition, and should be changed to trimethobenzamide (Tigan), Zofran, Anzemet, or other less offensive medications. Not only is Tigan free of sedation, but it is unaccompanied by risks to cause irreversible tardive dyskinesia. Reglan is a proconvulsant agent.(46) It can cause irreversible tardive dyskinesia after a single dose.(100) The incidence of adverse extrapyramidal reactions from Reglan is as high as 1 in 500, and the spectrum encompasses not just irreversible tardive dyskinesia, but also orofacial dyskinesias, akathisia, chorea, tremor, dystonia, and parkinsonism.(100) Involvement of the diaphragmatic respiratory and buccolingual deglutition muscles may cause life threatening dyspnea and dysphagia, necessitating gastrostomy tube placement for nutritional support.(159) This is truly regrettable if the intracranial pathology improves, allowing a 20 year old to return to independent living with the iatrogenic condition of irreversible tardive dyskinesia, precluding optimal socialization and quality of life.
For analgesia, opioid narcotics can suppress cognition, and should be second options to Tylenol, NSAID's, and ice, heat, or TENS modalities.
Antihypertensive agents which are sedating and otherwise cognitively offensive include clonidine,(55) alpha-methyldopa,(109) and lipophilic beta blockers.(89) Reserpine is proconvulsant.(46) More desirable alternatives include hydrophilic beta blockers, ACE inhibitors,(19) calcium channel blockers, and thiazide diuretics.(19) Beta blockers have particular utility to selectively extinguish aggressive disinhibited behavior.
Lipophilic beta blockers cross the blood brain barrier and can induce sedation, depression, insomnia, visual illusions, spatial memory compromise, hallucinations, psychosis, and perceptual motor deficits.(89) Hydrophilic agents do not cross the blood brain barrier, and are the indicated agents if the sole goal of delivering the beta blockers is control of systemic cardiovascular function. The most highly lipophilic beta blocker is propranolol. Those with moderate lipophilicity include timolol, metoprolol, pindolol, and labetolol. Those which are most hydrophilic include nadolol, acebutolol, and atenolol. Acebutolol and atenolol are also cardioselective(10) with decreased risk of exacerbating bronchospasm at lower doses.
Restoration of impaired sleep-wake cycles may be achieved safely with melatonin. Foods with high contents of tryptophan such as milk and turkey may promote sleep. Avoidance of daytime naps and abstaining from coffee, tea, and other caffeine containing foods close to bedtime may also promote faster falling asleep, avoidance of nocturnal wakenings, and restorative sleep quality with refreshed awakening. Sleeping in a cool room decreases core body temperatures and may promote sleep by increasing endogenous melatonin concentrations.(145)
Melatonin 0.3-75 mg po qhs may promote high quality sleep, especially in the elderly, a population in whom endogenous melatonin secretion is often diminished.(145) Onset of effect may be delayed 1-3 days, but melatonin may increase daytime alertness, reduce sleep fragmentation, diminish time to sleep onset, decrease nocturnal awakenings, without changing REM quality sleep, inducing morning hangovers, causing mood depression, or next day sedation.(145) As an endogenous substance, melatonin is extremely safe. The FDA chose to classify melatonin as a nutritive/dietary supplement, and so products are poorly regulated with unidentifiable impurities in products from some manufacturers.(145) Patients with major allergies or autoimmune disorders may also wish to abstain from melatonin as it may stimulate the immune system.(145)
Trazodone is an excellent second option in females, but should not be given to males in light of well documented risks of iatrogenic, idiopathic priapism which may require emergent surgical reduction with accompanying risks for irreversible impotence. Reports indicate incidences ranging from 1 in 23,000 male users(4) to 1 in 6000, with abrupt manifestation within 3 days -18 months of use.(61) Trazodone (Desyrel) dosing is 75 mg po qd to 600 mg po qd.(55) Trazodone requires further investigation, as transient delay in motor recovery occurred in rats with use of this agent.(30) Chloral hydrate, 250-1500 mg qhs is another choice, but should be used with caution in the patient with hepatic or renal compromise. Short term use of an ultra-short acting benzodiazepine such as Restoril may re-establish sleep-wake cycles, as a desirable third line agent in an older patient with impaired drug clearance. To promote sleep in the cognitively impaired, neuroleptics should be the last agents considered. Neuroleptics are well documented as impairing neurologic recovery after intracranial events.
The clinician must reassess the indication for anticonvulsants. If such drugs are necessary, more sedating agents should be tapered after therapeutic levels of less offensive agents are achieved. A taper of phenobarbitol faster than 15 mg a month may precipitate withdrawal siezures.
The clinician should assess if the anticonvulsant is still necessary or if it can be projected to be tapered in 1-3 months while the patient is observed in the hospital. Maximal cognition and antiseizure efficacy can be achieved if monotherapy is pursued instead of cumulative toxicity of polytherapy.(158) Clinicians should strive to prescribe dosing such that the lowest level in the therapeutic window is achieved, as anticonvulsants impair speed of thought processing, attention, and memory more extensively at higher therapeutic window serum levels relative to lower serum levels.(103,110,131) These effects may be more pronounced after initiation of drug therapy(110) at the time when patients are attempting to achieve the maximal benefit from rehabilitation therapies. Many patients, however, become sedated when anticonvulsants just reach the low end of the "therapeutic window." If antiseizure efficacy is appreciated with negligible cognitive side effects despite "subtherapeutic" serum levels, then clinicians should seek informed consent to maintain patients "subtherapeutic" yet seizure free.
Patients are often placed on Dilantin or phenobarbital in the acute care hospitals to take advantage of their capacity for rapid I.V. loading. However, phenobarbital has been conclusively proven to be amongst the most cognitively offensive anticonvulsants. Dilantin impairs arousal, concentration, memory, and speed of mental processing.(35,110) In addition, chronic delivery of Dilantin predisposes to cerebellar degeneration, sensory peripheral neuropathy,(35) and gingival hyperplasia with consequent dental caries. Dilantin induced impairment in folate transport and biologic utilization predisposes to mood depression and macrocytic anemia.(35) In patients receiving Dilantin, carbamazepine should be added and Dilantin tapered when the carbamazepine is therapeutic, as Dilantin has been shown to adversely affect cognition more than carbamazepine.(140,143,152) If treatment with Dilantin cannot be substituted for alternative agents, then the clinician should supplement the diet with folate to avoid deficiency effects on cognition and red cell synthesis. Also, Dilantin should be given in one large evening oral dose up to 500 mg to facilitate sleep and limit daytime sedation. Some individuals may also find valproate to be less sedating than phenytoin. An occasional individual may exhibit paradoxically improved cognition on Dilantin relative to carbamazepine.
MEDICATION TRIALS - GENERAL CONCEPTS
Benefits of early treatment with psychostimulants to enhance AAI should be viewed favorably as the same agents may mediate motor and speech recovery. In addition, these agents may successfully prevent disinhibited behavior from manifesting, presumably by enhancing attention quality as the patient ascends from lower levels of consciousness. AAI as well as disinhibited behavior may be responsive to amantadine.(64)
If the aforementioned more conservative interventions are suboptimally effective in enhancing suboptimal cognition, then active drug trials are indicated. Documented consent for these trials should be sought. Though miraculous clinical improvement often occurs, the FDA has not yet approved many of these drugs for treatment of deficits in AAI. Documentation must include indication for drug trial, specific short and long term target goals, and manner of monitoring for side effects. A number of additional general considerations must be recognized;
If the clinician has the luxury of waiting an entire week after dose changes, this should be embraced as it may more clearly support a direct cause effect relationship in improving AAI. If a limited inpatient stay is expected and rapid dosing to maximize AAI does precipitate psychosis, then the clinician should slowly taper the stimulants. Antidopaminergic neuroleptics should be prescribed only as a last resort. Patients with premorbid histories of psychotic thought disorders may require more careful monitoring.
Patients must be monitored for the effects of excessive psychostimulation, including perseveration, psychosis, and increased inaccuracies as the speed of processing and the error frequency of data manipulation may occur.
Inefficacy or intolerance of a medication does not preclude similar response to other psychostimulants and patients deserve multiple trials at ascending dosing. Protriptyline may enhance AAI despite inefficacy of another noradrenergic agent, methylphenidate.(114) Bromocriptine may effectively treat akinetic mutism refractory to high doses of methylphenidate and Sinemet.(102) Efficacy of Sinemet to dramatically enhance motor function in locked-in-syndrome despite an unsuccessful trial with the dopaminergic bromocriptine has been reported.(50) These reports should be recognized as a reflection of the infancy of medical knowledge of synaptic neurophysiology. It has been suggested that only 5% of central nervous system neurotransmitters have been identified.( ) This also describes postsynaptic receptor subclassifications and receptor interactions. As such, it is entirely unsurprising that agents have numerous as yet undefined bioactive properties despite classical oversimplified classification as dopaminergics, noradrenergics, serotonergics,... This schema, however, is a valuable foundation apon which to expand as knowledge accumulates. Investigation of dopamine 1,2,3,.. receptors, alpha or beta adrenergic receptors, and muscarinic and nicotinic receptors is invaluable to direct pharmaceutical engineering of specific pre- and post-synaptic agonists and antagonists.
Psychostimulants may cause paradoxical sedation. However, if cognition abruptly declines, then a delirium workup must be emergently repeated, as syndrome of inappropriate ADH secretion, meningitis, appendicitis, urinary tract infection, or other potentially life threatening medical condition must be excluded prior to attribution of the decline to the psychostimulant. This may save the patient's life as well as avoid documentation of intolerance to a particular psychostimulant. Although numerous drug options exist, the selection is finite, and recording an adverse drug reaction may preclude delivery of that agent for the entirety of the patient's life.
Because inpatient lengths of stay are markedly abbreviated relative to prior years, aggressive psychostimulant drug trials are often indicated before a baseline low level of cognition has been established. In addition, psychostimulants may facilitate neurologic recovery of cognition.
Excessive psychostimulation may result in perseveration and/or disinhibition.(116)
Patients often spontaneously improve over time. As such, drugs should slowly be tapered after a month or two of use to assess if administration is still necessary. Worsening of cognition during a trial taper is an indication to reinstitute drug delivery.
Add only one new medication at a time. Otherwise, improvements or side effects cannot be attributable to any single drug. Paradoxical impairments in cognition with psychostimulants may occur. At doses of bromocriptine presynaptic activity exceeds postsynaptic activity, and antidopaminergic activity prevails.( )
Tachycardia with resultant increased risk for myocardial ischemia or fatal arrhythmia may accompany treatment with several psychostimulants, in particular noradrenergics agents. Atenolol or nadolol are cardioselective with low lipophilicity and accompanying low risk to enter the brain. These beta blockers may be delivered with psychostimulants for their cardioprotective properties. Beta blockers also exhibit prophylactic efficacy to diminish cardiac irritability from potential proarrhythmic psychostimulants.
Anorexia is a common side effect of psychostimulants. Treatment with Megace or other appetite stimulants may afford tolerability of drugs to enhance AAI. Similarly, nausea may accompany prescription of psychostimulants, and use of trimethobenzamide (Tigan), Kytrel, Zofran, Anzemet, or other agents may be dosed prophylactically. Alternatively, if the clinician has the luxury of slow escalation in dosing, these transient side effects may be avoided.
Chorea and tics may occur at higher doses, as may perseveration.
Allow days to a week for medication dose increases to effect improvement.
Nurses and therapists often spend more time with patients than do physicians, and they can give a more extensive input with respect to response to pharmaceutical agents and dose levels. The final test whether or not the drug is effective can be conducted by the clinician tapering the drug and asking the therapists and nurses if they note any change. Therapists assume the role of being blind to knowledge of medication changes, and their observations may become more objective. At an unpredictable dose, cognitive improvement fails to continue with serially elevated dose, but dose dependent toxicity continues to accumulate. In addition, excessive delivery of psychostimulants may engender cognitive toxicity, manifested as hyperattentiveness to environmental distractors, perseveration, psychosis, and disinhibited behavior. The clinician must assume a leadership role to educate the team that the drug is not "bad," and maintenance at a slightly lower level may be beneficial to the patient. Neuropsychological testing may be helpful before and during drug trials to provide objective test data to guide ongoing treatment.
A patient who may have failed one psychostimulant may be very responsive to one of the same or different class, not unlike the efficacy of a different NSAID in relieving the pain of muscle strains when minimally structurally different compounds have proven ineffective. The optimal course of action is a clinical trial.
Drug trials are individualized to the patient's medical history and current status. Seizure disorder, neurogenic bladder, hepato-renal dysfunction, coronary artery atherosclerosis, and other aspects of systemic medical status are critically assessed in terms of drug side effect profiles. Dosing must also be considered after assessment of bioavailability, drug clearance, pharmacokinetics, and pharmacodynamics.
Drugs with high anticholinergic properties may induce urinary retention. This is especially a concern in patients with prostatic enlargement anatomic barrier to voiding as well as in patients with pathophysiologic external sphincter spasticity. Co-treatment with Urecholine, Baclofen, and other interventions may be required to facilitate bladder contractility to counter urinary retention related to noradrenergic mediated increased smooth muscle internal sphincter tone.
Orthostasis may occur as a result of dopaminergic effects on arterial vasocontractility. Cotreatment with Proamitine or Flurinef may be required if refractory to thigh high stockings, corsets, positioning, isometrics, and other non-pharmacologic pursuits.
Side effects which occur with initial rapid increase titration in dosing may remit when the dose of the agent is lowered. Subsequent retrial after a one to two week intake of a lower dose may enhance tolerability.
Patients with seizure disorders or significant risks for development of post-traumatic seizures may preferentially be treated with bromocriptine,(18,117) doxepin,(21) valproic acid, and carbamazepine, as these drugs have anticonvulsant properties. Amantadine has been described as being proconvulsant(25,43) as well as anticonvulsant.( ) Ritalin may be anticonvulsant(17) or have no effect on seizure threshhold.(17,43) Sinemet may have weak proconvulsant properties.( ) Amitriptyline, desipramine, and protriptyline are tricyclic antidepressants which are proconvulsant.(20) Amitriptyline may be less so than other tricyclics.(4,54) Secondary amines may be safer antidepressants than tertiary amines.(61) Bupropion, at doses greater than 450 mg qd, increases the risk for seizures.(11) Fluoxetine and MAOI's do not markedly increase seizure risk.(43) Concomitant dosing with anticonvulsants for posttraumatic seizure prophylaxis may reassure the clinician that the patient is at lower risk for seizures. Use of lower doses of potentially proconvulsant psychostimulants should be pursued, if possible. Patients must be educated to fully abstain from even small amounts of alcohol to avoid lowering the seizure threshhold.
Less severely brain injured patients exhibit improved memory, attention, and initiation with psychostimulants, and those with severe injuries respond with improved levels of arousal.
Excessive dosing may result in perseveration,(34) aggression,(34) emotional lability,(34) psychosis, auditory hallucinations, or agitation. Choreaform movements and tics may result from psychostimulants.(34) If this occurs, then dosing should be minimally reduced such that maximal benefit is achieved. Stimulant induced irreversible Gilles de la Tourette's syndrome may occur in predisposed individuals,(68) and these agents are relatively contra-indicated in patients with personal or family histories of tics. Side effects relative to dosing are individually variable. Ritalin greater than 10 mg a day may decrease therapy participation in one individual,(114) but may be suboptimal to effect psychostimulant efficacy in a second individual who might maximally benefit from 40 mg a day.
Patients may exhibit variable patterns of response to medications. Some individuals may slowly and progressively respond to greater and greater doses. Other patients may remain unresponsive until a modest dose increase suddenly precipitates a marked positive response.
Research has not advanced enough to be able to predict which head injured patients should be treated with which psychostimulants, and symptomatic considerations must guide prescriptions, pending controlled trials.(2)