- Design
- Cochrane systematic review and meta-analysis of randomised trials
- Population
- 11 trials, 714 people with acute schizophrenia or similar major mental illness
- Primary outcome
- Tranquillisation and sedation, 15 minutes to 48 hours
- Effect
- Tranquillisation at 15 min RR 2.27 (0.89 to 5.81); more sedation at 24 h (RR 0.25, 0.11 to 0.54)
This Cochrane review update, published 24 September, pooled 11 randomised trials with 714 people with acute schizophrenia or similar illness who received intramuscular zuclopenthixol acetate for acute behavioural disturbance, compared with standard drugs such as haloperidol with or without promethazine.
There was no clear difference in tranquillisation at 15 minutes (RR 2.27, 95% CI 0.89 to 5.81; one trial), in global state, mental state, aggression or adverse effects. Haloperidol plus promethazine probably sedated more people at 15 minutes, while zuclopenthixol acetate probably sedated more at 24 and 48 hours. Fewer additional benzodiazepines were needed with zuclopenthixol acetate, but this rested on one trial and was very uncertain. Doses of 25–50 mg looked as effective as 50–100 mg, again on very uncertain evidence.
The drug is often chosen on the belief that one injection calms the patient for two or three days. The review suggests it does not act faster or better, and the longer sedation it produces is a monitoring burden rather than a clear benefit. Selective reporting affected 10 of the 11 trials.
- Do not use zuclopenthixol acetate as first-line rapid tranquillisation; it is not faster than haloperidol with promethazine.
- Expect sedation to persist at 24 and 48 hours after a dose, and plan physical observations accordingly.
- Where it is used, the lower 25–50 mg dose appears as effective as higher doses.
- Reserve it for patients with a history of repeated parenteral doses, not for the drug-naive.
Why it matters
Challenges the habit of reaching for a single long-acting injection to cover several days of disturbance.
Don't overread it
Low-quality trials with selective reporting — "no difference" here means no demonstrated difference, not proven equivalence.
The statistics, in plain English
Most comparisons came from one or two small trials, so confidence intervals are wide — the 15-minute tranquillisation estimate runs from slightly worse to nearly six times better. That is uncertainty, not evidence of benefit.
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