title: Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Applied Health Sciences (Mental Health), University of Aberdeen, Aberdeen, UK. ark_jayakody@yahoo.com.
authors.forename: Kaushadh
authors.initials: K
authors.lastname: Jayakody
authors.forename: Roger Carl
authors.initials: RC
authors.lastname: Gibson
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.forename: Shalmini
authors.initials: S
authors.lastname: Gunadasa
mesh_terms: D000208:Acute Disease; D000374:Aggression / Q000187:drug effects*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D003006:Clopenthixol / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D014754:Violence / Q000523:psychology
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D003006:Clopenthixol; D006220:Haloperidol; C084602:clothiapine