Objective: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or ...
BRIEF REPORTS
Intramuscular Flunitrazepam Versus Intramuscular Haloperidol in the Emergency Treatment of Aggressive Psychotic Behavior Abraham Dorevitch, Pharm.D., Nachum Katz, M.D., Zvi Zemishlany, M.D., Dov Aizenberg, M.D., and Abraham Weizman, M.D.
Objective: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients. Method: Twenty-eight actively psychotic inpatients, aged 20– 60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. Results: Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes. Conclusions: Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings. (Am J Psychiatry 1999; 156:142–144)
B
enzodiazepines have recently gained interest as a class of drugs for use as alternatives or adjuncts to ongoing antipsychotic agents in emergency settings (1). Lorazepam and diazepam, administered parenterally, have been shown to be a good alternative to parenteral haloperidol for the immediate control of psychotic aggressive or disruptive behavior (2, 3) and as an adjunct to lithium in the clinical management of early manic agitation in bipolar patients (4). Intramuscular lorazepam has emerged as the benzodiazepine of choice for immediate control of psychotic disruptive behavior (5). Alprazolam, when combined with haloperidol, is also particularly effective in the initial hours of treatment of acutely psychotic schizophrenic patients (6). Intramuscular clonazepam, however, acts more slowly than intramuscular haloperidol (7). Chlordiazepoxide and diazepam are rarely used because their intramuscular administration is associated with prolonged sedation and erratic absorption and is therefore not superior to oral administration (8). This is not true for Received Feb. 13, 1998; revision received June 24, 1998; accepted July 6, 1998. From the Talbieh Mental Health Center, Hebrew University Faculty of Medicine; and Geha Psychiatric Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Address reprint requests to Dr. Dorevitch, Talbieh Mental Health Center, 18 Disraeli St., P.O. Box 4487, Jerusalem 91000, Israel.
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flunitrazepam, whose intramuscular absorption corresponds to its absorption through the oral route (9). To date, flunitrazepam has been investigated primarily as a hypnotic agent in patients with insomnia and in anesthesiology (10). The purpose of the present study was to prospectively investigate the efficacy of intramuscular flunitrazepam versus intramuscular haloperidol in the acute treatment of aggressive psychotic inpatients. METHOD The study group included 28 patients (13 men and 15 women), of whom 19 had schizophrenia, seven had schizoaffective disorder, and two had bipolar disorder. All diagnoses were established according to DSM-IV criteria after a clinical interview in which the guidelines of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (11) were used. Inclusion criteria for the study were the presence of active psychosis; disruptive or aggressive behavior, pronounced psychomotor agitation, or violent outbursts; and hospitalization in an acute ward. Patients were assigned by a table of random numbers, on a double-blind basis, to receive either 5 mg i.m. of haloperidol (N=13, five men and eight women; mean age=36.8 years, SD=15.1) or 1 mg i.m. of flunitrazepam (N=15, eight men and seven women; mean age= 34.9 years, SD=8.1) during an acute aggressive outburst. Follow-up evaluation was performed with the Overt Aggression Scale (12), a 16-item index specifically designed to assess verbal and physical aggression toward objects, the self, or others. Measurements were
Am J Psychiatry 156:1, January 1999
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made at baseline and at 15, 30, 45, 60, 90, and 120 minutes. All ratings were completed by the same rater (N.K.), who was blind to the study medications. Overall response to treatment was defined as a reduction of at least 50% in Overt Aggression Scale score at 90 minutes. The Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) scale were also administered at baseline to assess the severity of psychotic symptoms. The study was approved by the institutional review board of the Geha Psychiatric Hospital, Tel Aviv. The need for informed consent was waived by the board, since both study medications are considered acceptable and consistent in clinical settings where rapid control of aggressive, disruptive behavior is needed. Repeated measures analysis of variance and Fisher’s exact test were used as appropriate in the statistical analyses.
FIGURE 1. Effects of Flunitrazepam and Haloperidol on Overt Aggression Scale Scores of Acutely Psychotic Aggressive Inpatientsa
RESULTS
There were no significant differences between the haloperidol and flunitrazepam groups in diagnostic entities (12 schizophrenic and schizoaffective disorders and one bipolar I disorder versus 14 schizophrenic and schizoaffective disorders and one bipolar I disorder), in BPRS variables (mean score=49.0, SD=6.6, versus mean=45.4, SD=6.7), and in CGI scores (mean=4.5, SD=0.5, versus mean=4.5, SD=0.7). The antipsychotic drug treatment was similar in both groups; in the haloperidol group: perphenazine, 5–20 mg/day (N=5); haloperidol, 5–10 mg/day (N=4); levomepromazine, 50 and 200 mg/day (N=2); and zuclopenthixol, 25 mg/ day (N=2); in the flunitrazepam group: perphenazine, 5–20 mg/day (N=4); haloperidol, 5–15 mg/day (N=6); levomepromazine, 75 mg/day (N=1); and zuclopenthixol, 25–50 mg/day (N=4). Four patients (two in each group) were taking additional medications including mood stabilizers (carbamazepine and valproic acid) and lorazepam. As shown in figure 1, the acute administration of either flunitrazepam, 1 mg i.m., or haloperidol, 5 mg i.m., resulted in a significant reduction in Overt Aggression Scale score (F=72.42, df=6, 156, p
