Zuclopenthixol acetate in the treatment of acute schizophrenia and similar serious mental illnesses

Background People with schizophrenia or other psychotic illnesses may have delusions or hallucinations that may lead them to be aggressive or violent to themselves or others. Medication that is used in this context requires the properties of rapid onset of effect (tranquillisation or at least initial sedation in order to quell aggressive or disorganised behaviour, but also antipsychotic effect), low frequency of administration and low levels of side effects, such as cardiological or neurological side effects, or pain at the injection site. Zuclopenthixol is the cis(Z)-isomer of clopenthixol, a neuroleptic of the thioxanthene group, used for treating people with psychotic symptoms. There is one oral preparation and two depot forms: zuclopenthixol acetate and zuclopenthixol decanoate. The acetate version does not stay in the body for very long (a single dose persists for only 72 hours) and is said to have these properties. Objectives To estimate the effectiveness of zuclopenthixol acetate for the acute treatment of serious mental illnesses in comparison to other neuroleptic drugs. Search strategy Searches of Current Controlled Trials (http://www.controlled-trials.com - accessed 5.10.2000), Cochrane Schizophrenia Group's Register of Trials (January 2001), the Cochrane Library (1997, CD-ROM, issue 2), MEDLINE (1966-1997) were supplemented by appeals for unpublished data to the research community and to the Medical Information Department of Lundbeck Limited. Attempts were made to contact relevant authors. Selection criteria Two reviewers independently assessed citations or papers and selected all randomised trials that included people with serious mental illnesses and compared zuclopenthixol acetate with other drug regimes. Data collection and analysis Two reviewers extracted data independently. Attempts were made to contact authors for additional or missing information. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for binary data. Where possible, OR were pooled using Peto method and intention-to-treat analysis undertaken. Mean differences were used for continuous variables. Main results Pooled data show no difference for the outcome 'no important improvement' in psychotic symptoms at the end of the follow-up period (OR 0.84 CI 0.34-2.05). Sedation was evaluated using different instruments. Only one study presented data which suggested an earlier and more intense sedation in zuclopenthixol acetate users at four hours (OR 0.18 CI 0.04-0.93). Use of additional antipsychotic medication was not avoided in the zuclopenthixol acetate group (OR 2.18, CI 0.64-7.42) and data on total number of administrations were not obtainable. Side effect data were poorly reported but there is no evidence of a consistent difference between zuclopenthixol acetate and other 'standard drugs' for either the pattern of side effects or the wish to leave the study early. Hospital and service outcomes, number of aggressive incidents, satisfaction with care and economic outcomes were not addressed by any study. Reviewer's 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 trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more effective in controlling aggressive/disorganised behaviour, acute psychotic symptoms, or preventing side effects. There were no data directly related to tranquillisation, but it may produce more earlier and intense sedation than oral haloperidol. Well-conducted randomised controlled trials are needed to confirm claims related to the use of zuclopenthixol acetate in emergency psychiatry.