Bruno Wroblewski

Lithium carbonate for aggressive behavior or affective instability in ten brain-injured patients.

Lithium carbonate (LiCO3) was used to treat 10 brain-injured patients with severe, unremitting, aggressive, combative, or self destructive behavior or severe affective instability. Five patients had a dramatic response that resulted in significant improvement in their participation in a rehabilitative program. One other patient had a moderate response. A seventh patient improved dramatically, but regressed after 7 wk. Three other patients had neurotoxic side effects that precluded continued use of the medication. Two of them were simultaneously taking neuroleptic agents. These case reports provide further evidence that LiCO3 can be a useful medication in the treatment of aggressive behavior and affective instability after brain injury, but that it has significant potential for neurotoxicity in this population, particularly when used in conjunction with neuroleptic agents.

The incidence of seizures during tricyclic antidepressant drug treatment in a brain-injured population

Tricyclic antidepressants (TCAs) have been associated with the occurrence of seizures both with overdoses and with therapeutic doses. Seizures with therapeutic doses of TCA have been reported in patients both with and without previous histories of seizures. The incidence of seizures possibly precipitated by TCAs was examined retrospectively in a population of 68 severely brain-injured patients, all of whom were at high risk for the development of seizures. Seizure histories, anticonvulsant use, comedication use, and other pertinent data were recorded before, during, and after TCA use. We conclude that 14 patients (19%) developed seizures largely caused by TCAs. Other possible contributing factors, clinical outcomes, and some recommendations are discussed.

The use of intramuscular midazolam for acute seizure cessation or behavioral emergencies in patients with traumatic brain injury.

Brain-injured patients involved in rehabilitation programs are susceptible to the occurrence of acute seizures or severe behavioral episodes. Effective pharmacological management in this setting should ideally include rapid onset without severe adverse effects. Previous treatments have generally included intramuscular diazepam or lorazepam, as well as intramuscular anti-psychotic drugs. These options have proved problematic due to poor absorption, slow onset of activity, or potential for unacceptable side effects. We report 10 cases involving the use of intramuscular midazolam, a rapid-acting, short half-life benzodiazepine, in treating acute seizures or behavioral problems. We conclude that this drug demonstrates great promise for the rapid, effective treatment of these conditions without significant adverse effects and deserves further study in these areas.

Twenty years of pharmacology.

During the past 20 years in pharmacology, a number of innovations have appeared that have resulted in significant changes in the drugs available for people with traumatic brain injury. Among the anticonvulsants, antidepressants, and antipsychotics, new drugs have appeared with fewer cognitive side effects. In these classes of drugs, as well as among central nervous system stimulants, once-daily or other sustained-release preparations have been introduced that make it considerably more likely that the patient will take his or her medication, with smaller fluctuations in drug levels as well. New drugs have also resulted in a greater number of medications for the clinician to choose from. The overall effect has been a dramatic change in pharmacology that has benefited people with traumatic brain injury.

Potentially toxic serum concentrations of desipramine after discontinuation of valproic acid.

Pharmacological interventions in the treatment of various cognitive, behavioural and neurological problems after brain injury often may involve combinations of medications from various drug classes. This carries the implication of potentially new or previously underreported drug interactions. A case report is presented in which a commonly used anticonvulsant drug, valproic acid, and a commonly used antidepressant, desipramine, interacted in such a manner as to cause potentially toxic serum concentrations of desipramine. This case demonstrates the important point that it is not simply the addition of one drug to another that may cause interaction, but the withdrawal of a particular drug which may then adversely impact the remaining drug regimen.

Quantification of attention-related behaviors in individuals with traumatic brain injury. A pilot study.

&NA; Whyte J, Rose T, Glenn MB, Gutowski W, Wroblewski B, Reger J: Quantification of attention‐related behaviors in individuals with traumatic brain injury: a pilot study. Am J Phys Med Rehabil 1994;73:2‐9 Clinical disorders of attention are common after traumatic brain injury but objective measures of their nature and severity are lacking. We developed a standardized independent work task to be performed by patients in a controlled, distracting environment. Videotaped records of patient behavior were made and coded in 15‐s intervals for on‐task behavior, presence of distractors and presence of extraneous motor behavior. Interrater reliability was good to excellent across eleven testing sessions involving four patients. This evaluation system revealed clinically important differences in on‐task behavior among the four patients, as well as different levels of distraction in response to external stimuli. It also showed effects of different tasks and repeated sessions. These data indicate that this evaluation system and accompanying coding process are reliable and provide preliminary evidence that they produce clinically valid results.

The cytochrome p-450 drug metabolizing enzyme system: an overview of potential clinically important drug interactions.

Bruno Wroblewski, MS, Rph, CGP Senior Consultant Clinical Pharmacist NeighborCare Woburn, Massachusetts OVER THE PAST decade, there has been an explosion of new drugs that have often been promoted as being safer. New antidepressants, atypical antipsychotics, and anticonvulsants in many cases may indeed be relatively safer than previously available agents. However, there has also been a significant and well-established literature during this same period focusing on medication-related problems and medication safety and errors, including drug-drug interactions. In particular, information regarding the cytochrome p-450 drug (Cyp-450) metabolizing isoenzymes and increased awareness of their involvement in life-threatening drug interactions has become well-documented.1 Although a thorough review of the Cyp-450 system is beyond the scope of this forum, a general overview of the role of Cyp-450 and development of some potential clinically significant drug interactions will be described. The Cyp-450 enzyme system is a major metabolic pathway for drugs and other substances (e.g., steroids, prostaglandins). Knowledge of the substrates, inhibitors, and inducers of Cyp-450 isoenzymes can assist

Carbamazepine replacement of phenytoin, phenobarbital and primidone in a rehabilitation setting: effects on seizure control

Most patients who receive anticonvulsants after traumatic brain injury are treated with the sedative anticonvulsants phenytoin and/or phenobarbital, or perhaps primidone. However, there is considerable evidence demonstrating that these medications have a deleterious effect on cognitive function. Thus, in a rehabilitation setting, alternatives should be sought. Carbamazepine has been found to be relatively free of such effects, and would be an optimum alternative if seizure control were comparable. We have studied the effects of withdrawing phenytoin, phenobarbital and primidone, and using carbamazepine as the primary anticonvulsant in 27 patients at the Greenery Rehabilitation and Skilled Nursing Center for whom ongoing anticonvulsant treatment was considered to be necessary due to previous seizures or a high risk of the occurrence of seizure. We compared a 3 month baseline period (just prior to carbamazepine introduction or sedative anticonvulsant tapering), to a 3 month post-withdrawal period immediately following sedative anticonvulsant withdrawal, when carbamazepine was the sole anticonvulsant. In 20 out of 21 patients in whom carbamazepine replaced sedative anticonvulsants seizure control was essentially similar or somewhat improved. In only one patient did the substitution with carbamazepine result in a loss of seizure control. Six patients were initially receiving carbamazepine in combination with phenytoin and/or phenobarbital. The removal of phenytoin and phenobarbital, leaving carbamazepine as sole therapy, resulted in improved seizure control in three patients and no change in the other three. In the light of carbamazepines reportedly less detrimental effects on cognitive function and behaviour in other patient populations, it should perhaps be considered as a first line anticonvulsant, especially for patients in rehabilitation settings.