How effective is aripiprazole for calming people who are aggressive or agitated due to psychosis?

Background
People with psychosis may experience hearing voices (hallucinations) or abnormal thoughts (delusions) which can make them frightened, distressed and agitated (restless, excitable or irritable). Experiencing such emotions can sometimes result in behaviour that is aggressive or violent. This poses a challenge and dilemma for mental health professionals who have to diagnose and, often quickly, give the best available treatment to prevent those who are aggressive, harming themselves or others.

Aripiprazole is a medication that can be used to treat psychosis and also calm people who are aggressive or agitated due to psychosis. It can be taken by mouth or by injection (intramuscular). However, aripiprazole can also cause unpleasant side effects such as headaches, upset stomach, and excessive sleepiness or drowsiness.

This review looks for evidence from randomised controlled trials that assesses the effectiveness of intramuscular aripiprazole for people who are agitated and aggressive as a result of having psychosis.

Searching
The Information Specialist of the Cochrane Schizophrenia group ran an electronic search in 2014 and in 2017 for studies randomising adults with aggression due to psychosis to receive either injections of aripiprazole or injections of a placebo (dummy treatment) or injections of another antipsychotic. The search found 63 relevant records, referring to 21 trials. Review authors screened these records for inclusion or exclusion.

Main results
Only three studies could be included. Evidence is limited due to the small number of trials and poor quality of data reported. Fewer people receiving aripiprazole required more injections to become calm than those receiving placebo or haloperidol. Overall, aripiprazole caused a similar number of adverse effects to placebo or haloperidol. Compared to olanzapine, aripiprazole was less effective at calming people but caused less sleepiness or drowsiness

Conclusions
Some evidence is available, but is of poor quality, and it is difficult to make conclusions about aripiprazole's effectiveness from such data. Health professionals and people with mental health problems are therefore left without clear guidance concerning use of aripiprazole as a rapid tranquilliser. More research is needed to help people consider which medication is better at calming people down, has fewer adverse effects, and works quickly and rapidly.

Authors' conclusions: 

The available evidence is of poor quality but there is some evidence aripiprazole is effective compared to placebo and haloperidol, but not when compared to olanzapine. However, considering that evidence comes from only three studies, caution is required in generalising these results to real-world practice. This review firmly highlights the need for more high-quality trials on intramuscular aripiprazole in the management of people with acute aggression or agitation.

Read the full abstract...
Background: 

People experiencing psychosis may become aggressive. Antipsychotics, such as aripiprazole in intramuscular form, can be used in such situations.

Objectives: 

To evaluate the effects of intramuscular aripiprazole in the treatment of psychosis-induced aggression or agitation (rapid tranquillisation).

Search strategy: 

On 11 December 2014 and 11 April 2017, we searched the Cochrane Schizophrenia Group’s Study-based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials.

Selection criteria: 

All randomised controlled trials (RCTs) that randomised people with psychosis-induced aggression or agitation to receive either intramuscular aripiprazole or another intramuscular intervention.

Data collection and analysis: 

We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. We included studies that met our selection criteria. At least two review authors independently extracted data from the included studies. We chose a fixed-effect model. We analysed dichotomous data using risk ratio (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their CIs. We assessed risk of bias for included studies and used GRADE to create 'Summary of findings' tables.

Main results: 

Searching found 63 records referring to 21 possible trials. We could only include three studies, all completed over the last decade, with 885 participants, of which 707 were included for quantitative analyses in this systematic review. Due to limited comparisons, small size of trials and a paucity of investigated and reported 'pragmatic' outcomes, evidence was mostly graded as low or very low quality. No trials reported useful data for one of our primary outcomes of tranquil or asleep by 30 minutes. Economic outcomes were also not reported in the trials.

When compared with placebo, fewer people in the aripiprazole group needed additional injections compared to the placebo group (2 RCTs, n = 382, RR 0.69, 95% CI 0.56 to 0.85, very low-quality evidence). Clinically important improvement in agitation at two hours favoured the aripiprazole group (2 RCTs, n = 382, RR 1.50, 95% CI 1.17 to 1.92, very low-quality evidence). The numbers of non-responders after the first injection also favoured aripiprazole (1 RCT, n = 263, RR 0.49, 95% CI 0.34 to 0.71, low-quality evidence). Although no effect was found, more people in the aripiprazole compared to the placebo group experienced adverse effects (1 RCT, n = 117, RR 1.51, 95% CI 0.93 to 2.46, very low-quality evidence).

Aripiprazole required more injections compared to haloperidol (2 RCTs, n = 477, RR 1.28, 95% CI 1.00 to 1.63, very low-quality evidence), with no significant difference in agitation (2 RCTs, n = 477, RR 0.94, 95% CI 0.80 to 1.11, very low-quality evidence), and similar non-responders after first injection (1 RCT, n = 360, RR 1.18, 95% CI 0.78 to 1.79, low-quality evidence). Aripiprazole and haloperidol did not differ when taking into account the overall number of people that experienced at least one adverse effect (1 RCT, n = 113, RR 0.91, 95% CI 0.61 to 1.35, very low-quality evidence).

Compared to aripiprazole, olanzapine was better at reducing agitation (1 RCT, n = 80, RR 0.77, 95% CI 0.60 to 0.99, low-quality evidence) and had a more favourable effect on global state change scores (1 RCT, n = 80, MD 0.58, 95% CI 0.01 to 1.15, low-quality evidence), both at two hours. No differences were found in terms of experiencing at least one adverse effect during the 24 hours after treatment (1 RCT, n = 80, RR 0.75, 95% CI 0.45 to 1.24, very low-quality evidence). However, participants allocated to aripiprazole experienced less somnolence (1 RCT, n = 80, RR 0.25, 95% CI 0.08 to 0.82, low-quality evidence).