Biomedical subjects
B A Wroblewski
Publications and source records attributed to B A Wroblewski.
Effectiveness of valproic acid on destructive and aggressive behaviours in patients with acquired brain injury.
Valproic acid, a primary anticonvulsant drug, has recently been studied for purported effectiveness in disparate disorders of mood and behaviour. The psychopharmacological treatment of patients with acquired brain injury frequently includes numerous trials of psychotherapeutic drugs such as antipsychotics, benzodiazepines, antidepressants, and lithium, in an effort towards affective and behavioural improvement. In this report we describe and graphically depict the striking efficacy of valproic acid in reducing and improving destructive and aggressive behaviours in five patients with acquired brain injury. In all cases valproic acid was effective after other pharmacological interventions were not. Also, the addition of valproic acid was followed by neurobehavioural improvement rather quickly, often within 1-2 weeks. Advantages of valproic acid, in addition to its possible unique efficacy, include a lower propensity towards sedation and cognitive impairment, and thus a more robust potential for rehabilitation participation. Behaviours associated with affective disorders ranging along the affective spectrum from depression to dysphoric mania may be particularly amenable to valproic acid. The drug may also be beneficial in some cases in which another psychotropic anticonvulsant, carbamazepine, was not.
Antidepressant pharmacotherapy and the treatment of depression in patients with severe traumatic brain injury: a controlled, prospective study.
BACKGROUND: Untreated or poorly treated depression in patients who suffer from traumatic brain injury can result in greater functional disability and prolonged or ineffective hospital and rehabilitation stays. Literature available on the pharmacologic treatment of depression after traumatic brain injury is scarce. This study investigated in a controlled and prospective manner the use of desipramine, a tricyclic antidepressant, in a series of patients with severe traumatic brain injury. METHOD: Ten patients with severe traumatic brain injury and long-standing depression, as diagnosed by DSM-III-R criteria, were admitted to the study because of the intention to be treated with antidepressants. They were randomly assigned to blindly start on either desipramine treatment (N = 6) or placebo lead-in (N = 4). Patients starting with desipramine stayed on that drug; patients starting with placebo lead-in were blindly crossed over to desipramine after 1 month if there was no significant improvement demonstrated by DSM-III-R criteria. All rating clinicians, physicians, and patients were blind to actual treatment and any ratings data. DSM-III-R evaluations were done monthly. An affect/mood scale was done every 2 weeks. RESULTS: Of all patients evaluable using the DSM-III-R, 6 (86%) of 7 demonstrated resolution of depression and depressed mood during desipramine treatment. (Three received desipramine throughout the study; 3 others started taking placebo and crossed over to desipramine,) One patient refused evaluation on DSM-III-R throughout; 2 patients, both on desipramine, dropped out because of adverse effects (seizure, mania). In addition, there was statistically significant (p = .001) improvement over time and different rates of improvement over time in the treated and untreated groups for the affect/mood scale data. CONCLUSION: Results from this small study, utilizing a blinded, placebo lead-in design appear to (1) demonstrate the clinically significant effectiveness of desipramine in treating long-standing depression in a series of patients with severe traumatic brain injury, as rated with DSM-III-R criteria; (2) show statistically significant improvement on the affect/mood scale data, favoring the treated versus untreated (placebo lead-in) group.
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 antipsychotic 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.
Intramuscular midazolam for treatment of acute seizures or behavioral episodes in patients with brain injuries.
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Control of depression with fluoxetine and antiseizure medication in a brain-injured patient.
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Methylphenidate and seizure frequency in brain injured patients with seizure disorders.
BACKGROUND: Psychostimulant drugs such as methylphenidate are increasingly being used in patients with traumatic brain injury or other brain injuries for a variety of cognitive and behavioral problems. However, there is some reluctance among clinicians and family members to use methylphenidate in brain injured patients because of warnings of seizure occurrence, which are prominently reported by the product labeling included in the Physicians' Desk Reference. METHOD: We retrospectively studied the use of methylphenidate in 30 consecutive patients with active seizure disorders. We compared the seizure frequency in the 3 months before and after methylphenidate with the seizure frequency during methylphenidate treatment, using the Wilcoxon signed-rank test. RESULTS: Overall, the findings demonstrated a trend toward a lesser incidence of seizures in patients during methylphenidate treatment. Only 4 patients had greater seizure frequency during methylphenidate treatment, and 3 of these 4 were receiving tricyclic antidepressants. CONCLUSION: Methylphenidate can be safely used in brain injured patients, even those at high risk for seizures, as it was associated with a trend toward reduction (rather than increase) in seizure frequency in this population.
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.
Carbamazepine-erythromycin interaction. Case studies and clinical significance.
Because of significant and seemingly haphazard fluctuations in serum carbamazepine concentrations, we decided to investigate the possible link between erythromycin administration and potential changes in serum carbamazepine concentration. We studied four cases involving this combination. In every case, serum carbamazepine concentrations either rose dramatically (doubled or tripled previous steady-state concentrations) or dropped precipitously once erythromycin therapy was discontinued. In all cases, we report serum carbamazepine concentrations obtained before, during, and after concurrent erythromycin administration. We conclude that the combination of erythromycin and carbamazepine represents a clinically significant drug interaction and should be avoided where possible.
Once-daily administration of phenobarbital in adults. Clinical efficacy and benefit.
The clinical anticonvulsant efficacy of once-daily administration of phenobarbital sodium was evaluated in 29 adults with head injuries. All patients were initially well controlled, with therapeutic blood levels of phenobarbital obtained from divided dose regimens, ranging from two to four daily administrations. All therapies were then converted to once-daily administration of the total dose at bedtime. Twenty-six patients (93%) remained within normal therapeutic blood levels without any dose change. Phenobarbital can safely, and perhaps should, be administered in a once-a-day regimen, with resultant benefits of probable increased compliance and decreased daytime sedation, if administered at bedtime.
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 carbamazepine's 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.
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.