Evaluating the usage of droperidol in acutely agitated persons with brain injury.

The objective of this study was to compare the effectiveness and safety of intramuscular droperidol to other intramuscularly administered agents used in the management of acutely agitated patients. Twenty-seven inpatients with a history of brain injury were prospectively monitored over a period of 2 months. Data collected for each episode of agitation include: dose, number of doses, time to achieve an adequate response or calming effect, post-episodic functioning, treatment-emergent side effects, and other patient demographics. A retrospective medical records review was also performed on the same cohort, to compare clinical outcomes associated with other intramuscular agents previously used for acute agitation. Time to achieve calming was significantly shorter with intramuscular droperidol (mean = 27.0 minutes) compared to intramuscular haloperidol, lorazepam, or diphenhydramine (group mean = 36.2 minutes, p = 0.02). Of the three comparative agents, the time to achieve calming was the fastest with lorazepam (mean = 35.0 minutes), and slower with diphenhydramine (mean = 42.6 minutes) and haloperidol (mean = 43.0 minutes). Single doses of droperidol controlled agitation more frequently than did single doses of comparative agents, and there was less post-episodic sedation with droperidol following release from seclusion or restraints. Both groups were similar in regard to the incidence of treatment-emergent events. This data represents the first published experience supporting the effectiveness of droperidol in reducing acute agitation in persons with brain injury. Follow-up studies with prospective, double-blind, parallel treatment groups should be performed to validate these preliminary findings.

Cerebrospinal fluid monoamine metabolites and glucose metabolism in posttraumatic aggression.

BACKGROUND: This pilot study was conducted to determine if aggressive, post brain-injured patients have abnormal glucose metabolism or abnormal CSF monoamine metabolite concentrations as compared with non-aggressive, post brain-injured controls. METHODS: Subjects with a history of traumatic brain injury underwent a lumbar puncture and glucose tolerance test after a three-week medication wash-out period. Monoamine metabolite concentrations and glucose nadirs were compared between aggressive and control subjects. RESULTS: There were no statistical differences between the aggressive (n = 4) and control (n = 6) group with respect to age (28.5 +/- 15.7 versus 28.0 +/- 10.8), weight (72.5 kg +/- 14.1 versus 67.7 kg +/- 10.1) or number of months since brain injury (31.8 +/- 26.1 versus 33.3 +/- 23.3). There were no significant differences between the two groups in glucose nadirs following oral glucose challenge or in levels of CSF monoamine metabolite concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylglycol (MHPG), although a trend toward significance was noted between the MHPG groups (higher MHPG within aggressive group). CONCLUSIONS: The preliminary data suggest that glucose metabolism and CSF monoamine metabolite concentrations do not differ significantly from aggressive subjects to controls in persons with brain injury. Follow-up prospective studies with larger sample sizes are needed to evaluate these preliminary findings.

Validity of a cognitive computerized assessment system in brain-injured patients.

The primary objective of the study was to investigate the criterion validity of the Cognitive Drug Research (CDR) computerized system in assessing cognitive functioning among persons with brain injury or other organic illness. Understanding the cognitive effects of pharmacotherapy is important in improving long-term rehabilitation outcomes in persons with organic disorders. The CDR system evaluates cognitive skills of attention, short-term or working memory, long-term memory, and visuomotor and motor functioning. For validity testing, correlation coefficients were obtained from an analysis of CDR scores to IQ and Folstein Mini-Mental State Exam (MMSE) scores. Subtests of the CDR system that correlated with the MMSE were choice reaction time (R = -0.542, p = 0.04), spatial working memory (R = 0.938, p = 0.01), and word recognition (R = -0.949, p = 0.01). These tests primarily measured attention and working memory. Correlations between the CDR and IQ scores were not evident. In summary, the data suggest the CDR assessment system has high patient acceptability by persons with traumatic brain injury, and is a useful tool in assessing certain domains of cognition, specifically short-term memory, discrimination, and identification skills.

Cognitive effects of antipsychotic agents in persons with traumatic brain injury.

Over 1 million survivors of traumatic brain injury receive maintenance pharmacotherapy, of which a substantial number receive antipsychotic agents for the treatment of psychoses, agitation and aggression, and other maladaptive behaviours. In spite of the common clinical uses of antipsychotics, the cognitive risks versus benefits are unclear. The purpose of this study was to assess differences in cognitive functioning before, during, and after discontinuation of antipsychotic agents in inpatients undergoing rehabilitation for traumatic brain injury. Neuropsychiatric tests (Reys Auditory-Verbal Learning, Trail Making A&B, Digit Span Forwards and Backward) evaluating cognitive skills of verbal ability, visuomotor speed, memory, learning, attention, and spatial ability were administered to each subject at baseline (immediately prior to tapering or discontinuing antipsychotic), when taper reached 50% of baseline dose, 1 week after antipsychotic discontinuation, and 3 weeks after discontinuation. These data suggest that select areas of cognition improve after antipsychotic discontinuation in subjects with traumatic brain injury. The magnitude of improvement appeared to be greater after discontinuation with thioridazine, a low-potency agent, compared to haloperidol, a high-potency agent. Results, although very preliminary, support the hypothesis of cholinergic involvement in regulating cognitive processes, and this underscores the need for more systematic research in this area.

Pharmacotherapy of aggressive behavior.

OBJECTIVE: To review the definition, clinical characteristics, prevalence, etiology, neurochemistry, and pharmacologic treatment of aggressive behavior, and provide recommendations regarding the use of specific pharmacologic agents for treating aggressive behavior. DATA SOURCES: Data from the scientific literature were analyzed, interpreted, and summarized. An English-language MEDLINE search yielded clinical trials, case reports, letters, and review articles addressing the etiology and pharmacotherapy of aggression. STUDY SELECTION: Because few well-controlled studies are available in aggression research, all literature addressing the pharmacologic treatment of aggressive behavior, as well as the neurochemistry and psychobiology of aggressive behavior, was reviewed. DATA EXTRACTION: The literature was reviewed on the basis of the particular pharmacotherapy and the specific population used. A separate review of the treatment of aggressive behavior in the elderly was included. DATA SYNTHESIS: The literature was assessed for applicability to clinical practice and usefulness to the general clinician. Recommendations were made from the primary literature in conjunction with trends in clinical practice. Pharmacotherapy is a primary mainstay of treatment for aggressive patients. In individuals for whom behavioral intervention alone is unsuccessful, drug therapy should be initiated along with continued nonpharmacologic intervention. Short-acting benzodiazepines and high-potency antipsychotic agents are effective in treating acute aggression on a short-term or as needed basis. Agents such as lithium, beta adrenergic blockers, carbamazepine, valproic acid, buspirone, trazodone, serotonin reuptake inhibitors, and clozapine may be useful in the chronic management of aggressive behavior. Every attempt should be made to streamline drug therapy in patients with chronic aggression and comorbid psychiatric disorders. CONCLUSIONS: On the basis of available research and extensive clinical experience, lithium or propranolol should be considered as first-line antiaggressive agents in patients without comorbid psychiatric disorders. A minimum trial period for assessing drug efficacy should last at least 6-8 weeks at maximum tolerated dosages. Patients responding to pharmacotherapy should be reevaluated every 3-6 months, and periodic medication tapers and/or drug-free periods should be attempted.

Preliminary comparison of predictive and empiric lithium dosing: impact on patient outcome.

OBJECTIVE: To evaluate whether initiating lithium with predictive dosing compared with empiric dosing improves outcome in patients with manic symptoms. DESIGN: The study was a randomized, single-blind design and used the Modified Slattery predictive method. SETTING AND PARTICIPANTS: Eighteen inpatients at an urban psychiatric hospital with a Mania Rating Scale (MRS) score greater than or equal to 24 were enrolled. OUTCOME MEASURES: The study endpoint was defined as an MRS rating less than or equal to 14 or discharge from the hospital. Assessments (MRS, Brief Psychiatric Rating Scale, Clinical Global Impression, Systematic Assessment for Treatment of Emergent Events Scale, quality of life measures) were completed at baseline, on days 3 or 4 and 7 or 8, and weekly thereafter. RESULTS: The predictive group achieved a therapeutic concentration significantly sooner than did the empiric group (p = 0.004); however, the mean serum lithium concentration at discharge did not differ between the groups. The predictive group was taking significantly higher dosages of antipsychotics in chlorpromazine equivalents on day 3 or 4 (p = 0.05). Significantly fewer gastrointestinal/genitourinary adverse effects on day 3 or 4 were reported by patients in the predictive group (p = 0.04). No difference was found between groups with any rating scale or other pharmacokinetic or medication item. Even though the difference did not meet statistical significance, the predictive group's length of stay in the acute unit was three days shorter than that of the empiric group, which may represent significant cost savings. CONCLUSIONS: The preliminary data do not suggest that patient outcome is improved by using Modified Slattery predictive dosing; however, the suggestion of a shorter length of stay in a restrictive unit merits further evaluation.

Buspirone's efficacy in organic-induced aggression.

The objectives of this study were to (1) identify and characterize hospitalized patients with an organic-related psychiatric diagnosis who had received buspirone therapy and (2) assess the effect of buspirone on aggressive behaviors. A retrospective medical records review was conducted on all patients who were admitted to our psychiatric/rehabilitation facility over a 36-month period and who had received buspirone therapy. Monthly behavioral therapy records were used to determine the quality and quantity of aggressive-related behaviors. Study endpoint was reached in each subject when buspirone was discontinued or when records were unavailable. Twenty subjects, ranging in age from 15 to 55 years old (mu = 26.1 +/- 9.8), were identified for study. Nine (90%) of 10 subjects for whom data were available for at least 3 months showed an improvement in behavior by study endpoint, and 6 (60%) showed at least a 50% reduction in behavioral symptoms by study endpoint. Results from this study suggest that buspirone is well tolerated and may be effective in the treatment of aggressive and other maladaptive behaviors in individuals with an organic component to their psychiatric illness, particularly traumatic brain injury. Prospective, controlled trials are needed to validate these findings.

Effect of a clinical psychopharmacy consultation service on patient outcomes.

The effect of a psychopharmacy consultation service on outcomes in patients with psychiatric disorders was studied. The medical records of 30 randomly selected patients who had been hospitalized between August 1990 and July 1992 at a private psychiatric institution and who had been seen by the psychopharmacy consultation service during that period were reviewed. Data obtained included (1) patient demographics, (2) patient information generated by the psychopharmacy consultation, (3) the types of recommendations made by the psychopharmacy specialist and whether the recommendations were accepted by the physician, and (4) the clinical outcome. Forty-three psychopharmacy consultations for the 30 patients were evaluated. A total of 125 recommendations were made by the consultation service; of these, 75 (60%) were accepted. The consultations were divided into consultations for which at least a majority of the resulting recommendations were accepted by the physician (n = 29) and consultations for which less than a majority of the recommendations were accepted (n = 14). For the majority group, 23 (79%) of the 29 consultations were associated with a positive outcome, compared with 2 (14%) of the 14 consultations in the less-than-majority group. Similarly, positive outcomes were significantly more frequent in the majority-group patients (16/21 [76%]) than in the less-than-majority-group patients (2/9 [22%]). The frequency of positive outcomes was higher among patients for whom most of the recommendations of a clinical psychopharmacy consultation service were accepted than among patients for whom most recommendations were not accepted.

Profile of a sample of subjects admitted to an acute care psychiatric facility with manic symptoms.

A prospective survey was conducted on 155 consecutive subjects with manic symptoms admitted to an inpatient psychiatric facility to identify possible reasons for rehospitalization. Approximately one third were previously hospitalized at the same facility within the past month. Over half (57%) of the sample were admitted because of aggressive episodes. On admission, 80 percent were receiving carbamazepine or lithium for a mood disorder, and 52.3 percent were receiving multiple medications, of which antipsychotics accounted for over half. Forty-four percent of the sample had comorbid substance use on admission, with marijuana and stimulants accounting for the majority of illicit drug use. Medication noncompliance in 64 percent, and identifiable psychosocial stressors in 55 percent, were also likely contributors to rehospitalization. The data highlights specific treatment issues in the care of patients with a manic component to their illness, and suggests the need for individualized discharge planning with careful followup and continual patient education to assist in the transition from inpatient to society.

A longitudinal analysis of factors associated with morbidity in cocaine abusers with psychiatric illness.

We conducted a study to characterize a population of cocaine users who were referred to a state psychiatric institution, identify treatment problems including reasons for relapse, and develop strategies to improve treatment outcome. Using a data base system from a tertiary-care hospital emergency department, we identified a sample of 80 patients with a cocaine-related presentation who came to the emergency department and were referred to the psychiatric facility. Forty-six percent had consumed crack cocaine, and 65% reported ingesting cocaine with other drugs, half of them with alcohol. Suicidal ideation or attempt was the most common reason for referral. A retrospective review of 58 of the 80 referrals to the psychiatric facility showed that over half of the patients were given a concurrent psychiatric diagnosis and required hospitalization on an acute-care psychiatric unit. Sixty-two percent of those admitted had prior hospitalizations at the psychiatric facility, yet only five patients had received treatment for substance abuse. Seventy-four percent were readmitted to the psychiatric facility within 1 year of their index episode, with a higher rate of relapse among persons with dual diagnoses compared to cocaine users without dual diagnoses (p less than 0.05). Possible reasons for relapse included lack of referral for substance abuse treatment, nonintegrated treatment of psychiatric illness and substance abuse, lack of psychosocial support, and unresolved financial or job-related stressors. The data support increased funding to facilities that treat persons with dual diagnoses, and suggest the need to develop comprehensive treatment approaches involving a multidisciplinary team to address issues of mental illness and substance abuse concomitantly, and to identify and resolve stressors leading to relapse.

Pharmacologic treatment of cocaine abuse.

The recent surge in the use of cocaine has imposed increased financial burdens on society in terms of cocaine-related crimes, and funding for hospitalization/medical treatment and long-term rehabilitation programs. Unfortunately, healthcare costs secondary to chronic cocaine use are likely to increase in the future as drug research into cocaine abuse and effective treatment programs are severely lacking. This article reviews existing literature on treatment of cocaine abuse and is intended to serve as a practical guide to the general clinician involved in drug management of cocaine abuse. Antidepressant agents and the dopamine agonists are emphasized because most of the studies showing benefit have used these agents. Advantages and disadvantages of various interventions are objectively assessed. Additionally, specific implications for both acute and chronic management of cocaine abuse are given along with discussion and recommendations regarding comorbidity.