Aim of review
This review looks at whether haloperidol is effective for treating people who are agitated and aggressive as a result of having 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), leading sometimes to aggressive behaviour. This poses a significant challenge for mental health professionals, who have to quickly choose the best available treatment to prevent the risk of harm to both patient and/or others.
Haloperidol is a medication used for treating people with psychosis that can be taken by mouth or injected. As well as being an antipsychotic (preventing psychosis), it also calms people down or helps them to sleep.
In 2011 and 2016, the information specialist of the Cochrane Schizophrenia Group searched their specialised register for randomised trials that looked at the effects of giving haloperidol compared with either placebo or other treatments to people who are aggressive or agitated because they were experiencing psychosis.
Forty-one studies are now included in the review but information in these is of low-quality. Main results show that when compared with placebo or no treatment, more people having haloperidol were asleep after two hours. However, evidence is not strong. Results are made more complex by large variety of available treatments (24 comparisons).
The review authors conclude there is weak evidence that haloperidol calms people down and helps manage difficult situations. However, this is not based on good-quality trails and therefore health professionals and people with mental health problems are left without clear evidence-based guidance. 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 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 is based on a summary written by a consumer Ben Gray from Rethink.
Additional data from new studies does not alter previous conclusions of this review. If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs are available, sole use of haloperidol for extreme emergency 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. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries 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.
Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas.
To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others.
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register.
Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest 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. We included trials meeting our selection criteria and providing useable data.
We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest.
We found nine new RCTs from the 2016 update search, giving a total of 41 included studies and 24 comparisons. Few studies were undertaken in circumstances that reflect real-world practice, and, with notable exceptions, most were small and carried considerable risk of bias. Due to the large number of comparisons, we can only present a summary of main results.
Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n=220, RR 0.88, 95%CI 0.82 to 0.95, very low-quality evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95%CI 0.93 to 60.21, very low-quality evidence).
Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n=473, RR 0.78, 95%CI 0.62 to 0.99, low-quality evidence). More people in the haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95%CI 1.52 to 28.86, very low-quality evidence).
Four trials (n=207) compared haloperidol with lorazepam with no significant differences with regard to number of participants asleep at one hour (1 RCT, n=60, RR 1.05, 95%CI 0.76 to 1.44, very low-quality of evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95%CI 0.91 to 1.43, very low-quality of evidence).
Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95%CI 0.46 to 147.45, very low-quality of evidence).
Addition of promethazine was investigated in two trials (n=376). More people in the haloperidol group were not tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95%CI 1.18 to 2.16, moderate-quality evidence). Acute dystonia was too common in the haloperidol alone group for the trial to continue beyond the interim analysis (1 RCT, n=316, RR 19.48, 95%CI 1.14 to 331.92, low-quality evidence).