Zuclopenthixol dihydrochloride for schizophrenia

Zuclopenthixol dihydrochloride, administered orally, is one of the older generation of drugs (though still available and used worldwide) for managing the signs and symptoms of schizophrenia. This review found no long term randomised studies and very few studies that reported clinically meaningful data. Two trials compared zuclopenthixol with placebo, neither of which reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of movement disorder adverse effects compared with people on placebo, although compared with similar older antipsychotics, zuclopenthixol fared better and the risk of being 'unchanged or worse' was decreased. None of the findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a wide range of adverse effects. When compared with the newer generation of drugs, those taking zuclopenthixol were associated with no greater risk of being unchanged or worse compared with those taking risperidone, although the study size of trials was small. People allocated zuclopenthixol however, were prescribed anti-movement disorder medication more frequently than those treated with risperidone and many people left these short studies early (45% zuclopenthixol vs 30% risperidone).

If conclusions can be drawn from this to suggest that oral zuclopenthixol may have some clinical advantage over other older drugs in terms of global state, at least in the short term, this is an important finding. Although there is no information on service, functional, behavioural outcomes and clinically significant outcomes such as relapse, we think it should remain a choice in the treatment of those for whom older generation drugs are indicated.

Authors' conclusions: 

There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated.

Note: the 8 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.

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Background: 

Zuclopenthixol dihydrochloride, given orally, is commonly used for managing the signs and symptoms of schizophrenia.

Objectives: 

To determine the effects of zuclopenthixol dhydrochloride for treatment of schizophrenia.

Search strategy: 

We searched the Cochrane Schizophrenia Group's register (December 2004). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. To identify further trials we also contacted a pharmaceutical company and authors of relevant studies.

We updated this search July 2012, 8 trials have been added to the awaiting assessment section.

Selection criteria: 

We included all randomised controlled trials comparing zuclopenthixol dihydrocodine with antipsychotics or with placebo (or no intervention) for treatment of schizophrenia and/or schizophrenia-like psychoses.

Data collection and analysis: 

We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed articles and extracted data. For dichotomous data we calculated relative risks (RR) and the 95% confidence intervals (CI) and the number needed to treat (NNT) or number needed to harm statistics. For continuous data we calculated weighted mean differences with 95% CIs for non-skewed data.

Main results: 

We included eighteen trials involving 1578 people. Two trials compared zuclopenthixol with placebo and neither reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of experiencing extraparamydal symptoms compared with placebo (n=64, RR 5.37, CI 1.12 to 29.34 NNH 2 CI 2 to 31). Ten short trials (total n=478) compared zuclopenthixol with other typical antipsychotics. Risk of being unchanged or worse was decreased by allocation to zuclopenthixol (n=357, 7 RCTs, RR 0.72 CI 0.53 to 0.98, NNT 10 CI 6 to 131). No findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a whole range of adverse effects, including movement disorders (n=280, 6 RCTs, RR needing additional antiparkinsonian medication 1.07 CI 0.86 to 1.33) and general agitation (n=162, 3 RCTs, RR needing treatment with hypnotic/sedative drugs 1.09 CI 0.76 to 1.56). Fewer people allocated zuclopenthixol left in the short term compared with those given other typical antipsychotics (n=424, 22% vs 30%, 8 RCTs, RR 0.70 CI 0.51 to 0.95, NNT 12 CI 7 to 67). Three short trials (total n=233) compared zuclopenthixol with atypical antipsychotics. Zuclopenthixol was associated with no greater risk of being unchanged or worse compared with risperidone (n=98, 1 RCT, RR 1.30 CI 0.80 to 2.11). People allocated zuclopenthixol were prescribed antiparkinsonian medication more frequently compared to those treated with risperidone (n=98, 1 RCT, RR 1.92 CI 1.12 to 3.28, NNH 3 CI 3 to 17). Weight gain was equal for people allocated zuclopenthixol and those given sulpiride (n=61, 1 RCT, WMD 1.60 CI 8.35 to 5.15). Many people left these short studies early (45% zuclopenthixol vs 30% risperidone, n=159, 2 RCTs, RR 1.48 CI 0.98 to 2.22). The two isomers of zuclopenthixol, when compared in four short studies (total n=140), did not result in clearly different outcomes.