Haloperidol plus promethazine for psychosis-induced aggression

Huf G, Alexander J, Allen MH, Raveendran NS

Published Online:

November 9, 2011

When people suffer from hallucinations and delusions (psychosis) they can become agitated, scared or aggressive and will not respond very rapidly to other peoples’ reassurance or help. In some circumstances the clinical staff may be too busy to take time to help someone through this. In this situation medication is used to help agitated people relax and become more tranquil or to sleep. In low and middle-income countries the drugs used to do this cannot be too expensive. This review includes four trials of people who have received the drugs haloperidol (an antipsychotic) in combination with promethazine (an antihistamine) compared to some other medications when they have been aggressive in an emergency situation. These four trials included 1117 individuals in cities in India and Brazil. People were monitored for whether they were tranquil or asleep at twenty minutes to four hours and also for adverse effects and how well they were.

All the treatments work, albeit at different rates with midazolam (benzodiazepine) working the fastest and lorazipam (another benzodiazepine) the slowest. However there were more adverse effects in the benzodiazepine groups. The results for haloperidol plus promethazine between trials showed differences in outcome in the two geographical locations. In both Indian trials the percentage of people on haloperidol plus promethazine becoming tranquil or asleep at 30 minutes were 95 and 96% whereas in Rio de Janeiro it was 67 and 70%. The reason for this is not fully understood but it may be due to cultural expectations and to the environment of the emergency room. Haloperidol plus promethazine, worked faster than haloperidol alone or olanzapine alone, although at later time points there was no difference in the number of people asleep or tranquil. More movement adverse effects were experienced with haloperidol alone.

It is difficult to combine all the results as each trial compared haloperidol plus promethazine with a different drug. There were also differences in the environment in which the patients were treated. Because of the need to keep both staff and patients safe this is an area that could benefit from more research.

(Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)

Abstract (click to read)

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 from all 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 20 minutes intramuscular haloperidol plus promethazine was more 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.

This record should be cited as:

Huf G, Alexander J, Allen MH, Raveendran NS. Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD005146. DOI: 10.1002/14651858.CD005146.pub2

Assessed as up to date:

February 15, 2008

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Primary Review Group:

Schizophrenia Group

Health topics:

Mental health > Schizophrenia & psychosis > Antipsychotic medication: butyrophenone

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Haloperidol plus promethazine for psychosis-induced aggression

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