Review question

The aim of this review was to compare the tranquillising (calming) or sedative (sleepiness) effects of benzodiazepines, given alone or combined with other drugs compared with the effect of placebo (a pretend treatment), other drugs or non-drug treatments for people who are aggressive or agitated because they are experiencing psychoses.

Background

Acute psychosis is a rapid worsening of a person’s mental state where touch with reality is often lost. People may experience frightening delusions or hallucinations which are distressing and may cause agitated or aggressive behaviour. In urgent cases, this agitation or aggression may cause harm to the person experiencing the psychoses or others around them. To avoid such harm, rapid tranquillisation or sedation with medicines may be required. The most common medicines used to achieve a state of calmness or sedation are benzodiazepines and these can be given either alone or in combination with antipsychotics.

Searching

The original search for this review was carried out in January 2012 and subsequently two further update searches were run in August 2015 and August 2016. In total, these searches found 2497 records, which the review authors checked for inclusion or exclusion from the review. Authors included records only if they were randomised trials (clinical studies where people are randomly put into one of two or more treatment groups) that allocated people with acute psychosis who presented with agitation, violence aggressive behaviour (or a combination of these) to receive benzodiazepines either given alone or combined with any antipsychotics, versus placebo, antipsychotics alone or in combination with other antipsychotics/benzodiazepines/antihistamines or non-drug treatments.

Evidence found

In total, 20 trials were included. Overall, the quality of evidence was low or very low due to serious risk of bias and very small size of included trials. There was no clear difference in improvement between benzodiazepines and placebo, benzodiazepines and antipsychotics or benzodiazepines plus antipsychotics and benzodiazepines alone or antipsychotic alone. When benzodiazepines were compared with combined antipsychotics/antihistamines, there was a higher risk of no improvement in people receiving benzodiazepine alone but the evidence was of low quality. Only one study showed lower effect of combined benzodiazepines/antipsychotics versus combined antihistamines/antipsychotics. However, the evidence was of very low quality. In terms of side effects, people receiving benzodiazepines compared to antipsychotics had lower risk of presenting with symptoms such as shaking, tremors and slurred speech whereas the results for the sedation caused were unclear.

Conclusions

The existing trials are not informative enough to support or refute the use of benzodiazepines alone or in additional to other medicines when urgent tranquillisation or sedation with medicines is required. Although benzodiazepines alone may cause fewer side effects compared to older antipsychotics, when they are added on to other medicines this may lead to unnecessary side effects. Further studies are needed to provide good-quality evidence with robust conclusions to inform clinical practice and policies around rapid tranquillisation for people with psychoses who are aggressive or agitated.