Haloperidol for psychosis‐induced aggression or agitation (rapid tranquillisation)
Abstract
Background
Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited.
Objectives
To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis‐induced agitation or aggression.
Search methods
We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011).
Selection criteria
Randomised controlled trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects.
Data collection and analysis
We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects.
Main results
We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.
Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21).
Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).
Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).
Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to 1.43).
Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated in one larger and better graded trial (n = 316). More people in the haloperidol group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16). Significantly more people in the haloperidol alone group experienced one or more adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated haloperidol alone was too common for the trial to continue beyond the interim analysis (RR 19.48, CI 1.14 to 331.92).
Authors' conclusions
If no other alternative exists, sole use of intramuscular haloperidol could be life‐saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, could be considered unethical. Addition of the sedating promethazine has support from better‐grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor‐grade evidence. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a risk of additional harm.
After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real world practice.
PICOs
Plain language summary
Haloperidol as a means of calming people who are aggressive or agitated due to psychosis
People with psychosis may experience hearing voices (hallucinations) or abnormal thoughts (delusions) which can make the person frightened, distressed and agitated (restless, excitable or irritable). Experiencing such emotions can sometimes result in behaviour that is aggressive or violent. This poses a significant challenge and dilemma for staff. Mental health professionals have to diagnose and give the individual the best available treatment, often quickly, to avert the risk of the persons who are aggressive harming themselves or others.
Haloperidol is a drug that can be taken as by mouth or injected. As well as being an antipsychotic (preventing psychosis), it calms people down or helps them to sleep.
This review looks at whether haloperidol is effective for treating people who are agitated and aggressive as a result of having psychosis. Haloperidol was studied when used alone and was also compared to 18 other treatments (for example other antipsychotic medications). Thirty‐two studies were found but the information in these was poor in quality. The studies were small in size, with few participants and had a risk of bias. The studies tended not to be based in everyday clinical or real‐life settings.
The authors conclude that haloperidol calms people down and helps manage difficult situations. When compared with placebo (dummy treatment) or no treatment, more people having haloperidol were asleep after two hours. However, the evidence is not strong. This is made more complex by the large variety of available treatments (18 other treatments in this review). Health professionals and people with mental health problems are therefore left without clear guidance that is based on evidence from good trials. In some situations, haloperidol may be the only choice, but this is far from ideal because although haloperidol is effective at calming people down it has side‐effects (e.g. restlessness, shaking of the head, hands and body, heart problems). These side‐effects can be just as distressing as the psychosis and may act as a barrier that stops people coming back for future treatment. More research is needed to help people consider and understand which medication is better at calming people down; has fewer side‐ effects; works quickly and rapidly; and can be used at lower dosages (or less frequent injections).
This plain language summary was written by a consumer Ben Gray from Rethink.
