Haloperidol plus promethazine for psychosis-induced aggression

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Background: Health services often manage agitated or violent people, and for emergency psychiatric services such behaviour is particularly prevalent (10%). The drugs used in this situation should ensure that the person swiftly and safely regains composure. Objectives: To examine whether haloperidol plus promethazine is an effective treatment for psychosis induced agitation/aggression. Search strategy: We searched the Cochrane Schizophrenia Group's Register (January 2008). Selection criteria: We included all randomised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used. Data collection and analysis: We reliably selected, quality assessed and extracted data fromall relevant studies. For binary outcomes we calculated standard estimations of risk ratio (RR) and their 95% confidence intervals (CI). Where possible we estimated weighted number needed to treat or harm (NNT/H). Main results: We identified four relevant high quality studies. One compared the haloperidol plus promethazine mix with midazolam (n=301), one with lorazepam (n=200), one with haloperidol alone (n=316) and one with olanzapine IM (n=300). In Brazil, haloperidol plus promethazine was an effective means of tranquillisation with over two thirds of people being tranquil or sedated by 30 minutes, but midazolam was more swift (n=301, RR 2.9 CI 1.75 to 4.80, NNH 5 CI 3 to 12). In India, compared with lorazepam, more people were tranquil or sedated by 30 minutes if allocated to the combination treatment (n=200, RR 0.26 CI 0.10 to 0.68, NNT 8 CI 6 to 17). Over the next few hours of treatment reported differences are negligible. One person given midazolam had respiratory depression (0.7%, reversed by flumazenil); one given lorazepam (1%) had respiratory difficulty. About 1% of people given any haloperidol treatment experienced a seizure. By 20minutes intramuscular haloperidol plus promethazinewasmore tranquillising than intramuscular haloperidol (1 RCT, n=316, RR 0.65 CI 0.49 to 0.87, NNT 7 CI 5 to 17). Haloperidol given without promethazine in this situation causes frequent serious adverse effects (NNH 15 CI 14 to 40). Olanzapine is as rapidly tranquillising as the haloperidol/promethazine combination (1 RCT, n=300, RR tranquil or asleep at 15 mins 0.74 CI 0.38 to 1.41), but did not have an enduring effect and more people needed additional drugs within four hours (1 RCT, n=300, RR 0.48 CI 0.33 to 0.69, NNT 5 CI 4 to 8) and to be re-assessed by the doctor (1 RCT, n=300, RR 0.47 CI 0.30 to 0.73, NNT 6 CI 5 to 12). Authors' conclusions: All treatments evaluated within the included studies are effective. Benzodiazepines, however, have the potential to cause respiratory depression, probably midazolam more so than lorazepam, and use of this group of drugs outside of services fully confident of observing for and managing the consequences of respiratory distress is difficult to justify. Haloperidol used on its own is at such risk of generating preventable adverse effects that unless it is the only choice, this evidence directs that this sole treatment should be avoided. Olanzapine IM is valuable when compared with haloperidol plus promethazine but its duration of action is short and re-injection is frequently needed. Haloperidol plus promethazine used in two diverse situations in Brazil and India has much evidence to support its swift and safe clinically valuable effects. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.




Huf, G., Alexander, J., Allen, M. H., & Raveendran, N. S. (2009). Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD005146.pub2

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