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Medications for aggression and agitation

How is aggression and agitation relevant to schizophrenia?

Agitation and/or aggression are sometimes observed during a psychiatric emergency such as in onset of acute psychosis. Agitation typically includes irritability and restlessness, motor or verbal hyperactivity, uncooperativeness, and occasionally aggressive gestures or behaviour. This can pose a risk both to the individual, as well as the attending health care professionals, and so is important to manage this behaviour and prevent potential harm.

What is the evidence for treatments for aggression and agitation?

Moderate quality evidence found a small to medium-sized effect of less hostility with second-generation antipsychotics compared to first-generation antipsychotics, particularly when given in high doses (>500mg chlorpromazine equivalent).

For particular antipsychotics, moderate to high quality evidence found haloperidol was more effective than placebo for sedation, agitation, and mental state in the short term, but haloperidol induced more extrapyramidal symptoms. There were small benefits of aripiprazole over placebo for agitation and needing fewer additional injections, with no differences in side effects. Haloperidol had similar benefit to aripiprazole for aggression, but less need for an additional injection. Aripiprazole had less overall side effects than haloperidol.

Moderate quality evidence found olanzapine was more beneficial than haloperidol for sedation, agitation and adverse effects, particularly extrapyramidal symptoms. There was also less agitation and better global state with olanzapine compared to aripiprazole, although there was more somnolence with olanzapine. Haloperidol was more effective than risperidone for sedation and aggression but resulted in more akathisia. Ziprasidone had similar benefit to haloperidol for sedation and aggression but had fewer side effects. Droperidol resulted in less need for an additional injection than haloperidol.

Moderate to low quality evidence suggests a medium-sized benefit of 5-10mg of aerosol loxapine for reducing agitation compared to inhaled placebo.

For combination therapies, moderate to low quality evidence found people receiving adjunctive benzodiazepines were more likely to be sedated for up to one hour, but were not less aggressive after one hour, than those on antipsychotics alone. Parkinsonism was lower and somnolence was higher with adjunctive benzodiazepines. Haloperidol plus promethazine was more effective than haloperidol alone for sedation and resulted in fewer overall adverse effects, particularly dystonia. Risperidone plus clonazepam resulted in more overall adverse effects than haloperidol, particular extrapyramidal symptoms, with no differences in sedation or agitation.

October 2020
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Last updated at: 4:25 am, 30th August 2021
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