Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses

People with schizophrenia or other mental health problems often hear disturbing voices or see distressing things (which are called delusions, hallucinations and psychosis). Such experiences can be frightening and may lead people to be aggressive or show violent behaviour toward themselves or other people. Tranquilising drugs are medications that help people to sleep or calm down, and help stop aggressive or disorganised behaviour. An antipsychotic effect is also desirable to help stop the delusions and hallucinations. Tranquillisers should not have to be used often and also have few unwanted side-effects, such as pain at the injection site or uncontrolled shaking of the head and hands. Zuclopenthixol acetate is said to possess all these properties.  

Zuclopenthixol acetate is given by an injection and has an effect that lasts for about two to three days. This review looks at zuclopenthixol acetate for managing aggression or violence. The review did not find any evidence that zuclopenthixol acetate is more or less effective in helping to control aggression or violence, or in preventing unwanted side-effects than other drugs (such as haloperidol, chlorpromazine, clothiapine). It did not seem to work quickly and/or be rapid in calming people down. 

Zuclopenthixol acetate may result in less forced injections (where restraint of the patient is needed to enable treatment). Low doses of the drug (as low as 25 mg) may be just as good and effective as higher doses (up to 100 mg). 

Overall the review found limited information for claims made to support the use of this drug (for example: that it rapidly calms or sedates people; or that it is better than other drugs in emergency situations). Recommendations on the use of zuclopenthixol acetate for aggressive or violent behaviour therefore have to be viewed with caution.  

Evidence is very far from good and convincing. Most of the research on the subject is small in size, with few participants, of short duration and data poorly reported in the individual studies. But it does point to zuclopenthixol acetate being helpful for managing very disturbed people. In comparison to other drugs it is not any worse than others. Moreover, the whole area on the management of very disturbed people is under-researched and more research is necessary.

This Plain Language Summary has been written by a consumer: Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness, Email: ben.gray@rethink.org .

Authors' conclusions: 

Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most of the small trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Use of zuclopenthixol acetate may result in less numerous coercive injections and low doses of the drug may be as effective as higher doses. Well-conducted pragmatic randomised controlled trials are needed.

Read the full abstract...

Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties.


To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions.

Search strategy: 

We searched the Cochrane Schizophrenia's Group Trials Register (July 2011). We supplemented this by citation searching and personal contact with authors and relevant pharmaceutical companies.

Selection criteria: 

All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs.

Data collection and analysis: 

Two review authors extracted and cross-checked data independently. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. We used mean differences (MD) for continuous variables.

Main results: 

We found no data for the primary outcome, tranquillisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n = 40, 1 RCT, RR 0.60, 95% CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n = 134, 3 RCTs, RR 1.49, 95% CI 0.97 to 2.30) although additional use of benzodiazepines was less (n = 50, 1 RCT, RR 0.03, 95% CI 0.00 to 0.47). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n = 70, 1 RCT, RR 0.39, 95% CI 0.18 to 0.84, NNT 4, CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n = 148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74, 95% CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (< 20%). Three studies found no difference in the proportion of people getting blurred vision/dry mouth (n = 192, 2 RCTs, RR at 24 hours 0.90, 95% CI 0.48 to 1.70). Similarly, dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n = 192, 2 RCTs, RR at 24 hours 1.15, 95% CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n = 522, RR 0.85, 95% CI 0.31 to 2.31). One study reported no difference in adverse effects and outcome scores, when high dose (50-100 mg/injection) zuclopenthixol acetate was compared with low dose (25-50 mg/injection) zuclopenthixol acetate.