Intramuscular haloperidol plus promethazine is more effective and safer than haloperidol alone for rapid tranquillisation of agitated mentally ill patients.

Question: Is haloperidol alone more effective than haloperidol plus promethazine for rapid tranquillisation of mentally ill patients? Patients: 316 adults presenting to the psychiatric emergency room with agitation or dangerous behaviour requiring intramuscular sedation, for whom an attending doctor was available to record the diagnosis and severity of the episode. Setting: One psychiatric emergency room, Rio de Janeiro, Brazil; January 2004 to July 2004. Intervention: Single intramuscular injection of haloperidol (5 or 10 mg) or haloperidol (5 or 10 mg) plus promethazine (up to 50 mg). In the haloperidol alone group, 29% received 5 mg and 71% received 10 mg. In the haloperidol plus promethazine group 50% received 5 mg haloperidol and 50% received 10 mg. Outcomes: Primary outcome: proportion of patients tranquil (calm and non-agitated with no threatening behaviour) or asleep at 20 min. Secondary outcomes included: tranquil or asleep at 40, 60 and 120 min; need for further medical attention within 24 h; adverse events. Patient follow-up: Data available for 98.4% for the primary outcome; 100% analysed in conservative intention to treat analysis. METHODS Design: Pragmatic randomised controlled trial. Allocation: Concealed. Blinding: Unblinded. Follow-up period: 20 min following antipsychotic injection (primary outcome); 40, 60, and 120 min, 24 h and 2 weeks following (secondary outcomes). MAIN RESULTS Haloperidol plus promethazine increased the proportion of patients tranquil or asleep at 20 min compared with haloperidol alone (proportion tranquil or asleep: 72% with combined treatment vs 55% with haloperidol alone; RR 1.30, 95% CI 1.10 to 1.55). The combined treatment increased the proportion of patients asleep at 20 min (19% with combined treatment vs 8% with haloperidol alone; RR 2.33, 95% CI 1.26 to 4.27). There was no difference between interventions in the proportion of patients tranquil or asleep after 20 min (40 min: RR 1.07, 95% CI 0.95 to 1.20; 60 min: RR 1.07, 95% CI 0.97 to 1.17; 120 min: RR 1.03, 95% CI 0.96 to 1.11). Haloperidol plus promethazine increased the proportion of patients who did not need to have a doctor recalled (77% with combined treatment vs 65% with haloperidol alone; RR 1.18, 95% CI 1.02 to 1.36). Haloperidol alone increased the risk of serious adverse events compared with haloperidol plus promethazine (1% with combined treatment vs 7% with haloperidol alone; RR 0.09, 95% CI 0.01 to 0.68). Most of the serious adverse events in the haloperidol alone group were acute dystonia (10 cases vs none with haloperidol plus promethazine). CONCLUSIONS There is no benefit of giving haloperidol alone compared to haloperidol plus promethazine for agitated or aggressive patients with mental illness presenting to the psychiatric emergency room. The combination is faster acting and has reduced risk of serious adverse events. ABSTRACTED FROM Huf G, Coutinho ESF, Adams CE, et al. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine. BMJ 2007;335:869-72. [ABSTRACT FROM AUTHOR]