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There are only small differences between zuclopenthixol acetate and standard treatments: probably more people are sedated (in a sleepy state) at 24 and 48 hours when given zuclopenthixol acetate, and they may need fewer additional doses of benzodiazepines (a type of sedative medicine). Doses of zuclopenthixol acetate of 25 mg to 50 mg per injection may be as effective as doses of 50 mg to 100 mg per injection.
There may be no clear difference in side effects between zuclopenthixol acetate and standard medications.
Further high-quality studies are needed to better understand the benefits and risks of zuclopenthixol acetate.
What is schizophrenia?Schizophrenia is a serious mental health condition that can cause long-term disability and major disruption to daily life. People with schizophrenia may experience difficulty telling the difference between what is real and what is not (psychosis), including hearing voices (auditory hallucinations) or seeing things that are not there (visual hallucinations) and holding strong beliefs that are not true (delusions). These experiences can be frightening and distressing. At times, this distress may lead to aggressive or violent behaviour towards themselves or others. However, people with schizophrenia are also at increased risk of being victims of violence. Managing aggression and violence in people with schizophrenia is important and should aim to reduce negative attitudes from other people (stigma) and promote safe, respectful care. What medications are used to treat schizophrenia?Medications have a calming effect (tranquillising effect), reduce the feeling of being very worried or bothered (severe agitation) or aggression, and help induce sleep (sedative effect). Ideally, these medicines should treat psychotic symptoms (such as hallucinations and delusions), not be used too often and cause few side effects (for example, pain at the injection site or involuntary shaking).Zuclopenthixol acetate is an injectable antipsychotic medication that can last for two to three days. This review examined whether zuclopenthixol acetate is effective for managing psychosis, aggression or violence, compared with other standard medications used in mental health settings.What did we want to find out?We wanted to find out if zuclopenthixol acetate was better than the usual medicines to help manage short-term (acute) behaviour changes that people with schizophrenia may have. We looked at how quickly the medicines helped people to feel calm and sleepy, what their overall effect was on the person and their behaviour, and whether there were any unwanted side effects. What did we do?We searched for studies that looked at the drug zuclopenthixol acetate given to people with schizophrenia and similar major mental illnesses who were experiencing short-term (acute) behavioural disturbance, compared to other standard treatments. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.What did we find?We included 11 studies with a total of 714 people. We found only small differences between zuclopenthixol acetate and standard treatments. Probably more people receiving zuclopenthixol acetate were sedated around 24 hours after treatment, but not in the first 15 minutes. People given zuclopenthixol acetate may need fewer doses of benzodiazepines. Doses of zuclopenthixol acetate of 25 mg to 50 mg per injection may be as effective as doses of 50 mg to 100 mg per injection. There may be no clear difference in side effects between zuclopenthixol acetate and standard medications.What are the limitations of the evidence?Many of the included studies were small and had weaknesses in their design and reporting, so our confidence in the evidence is limited. Further high-quality studies are needed to better understand the benefits and risks of zuclopenthixol acetate.How up to date is this evidence?The evidence in this review is current to September 2025.
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