Haloperidol versus placebo for schizophrenia Item Type Article Authors Irving, Claire B.; Adams, Clive E. Citation Irving, C. B., Adams, C. E. & Lawrie, S. (2006). Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews, (4), pp.1-69. Download date 25/09/2021 21:20:50 Link to Item http://hdl.handle.net/20.500.12904/9860 Haloperidol versus placebo for schizophrenia (Review) Irving CB, Adams CE, Lawrie S This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2006, Issue 4 http://www.thecochranelibrary.com Haloperidol versus placebo for schizophrenia (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 3 METHODS ...................................... 3 RESULTS....................................... 6 DISCUSSION ..................................... 10 AUTHORS’CONCLUSIONS . 11 ACKNOWLEDGEMENTS . 11 REFERENCES ..................................... 12 CHARACTERISTICSOFSTUDIES . 25 DATAANDANALYSES. 67 Haloperidol versus placebo for schizophrenia (Review) i Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Haloperidol versus placebo for schizophrenia Claire B Irving1, Clive E Adams1, Stephen Lawrie2 1Cochrane Schizophrenia Group, The University of Nottingham, Nottingham, UK. 2Department of Psychiatry, University of Edin- burgh, Edinburgh, UK Contact address: Claire B Irving, Cochrane Schizophrenia Group, The University of Nottingham, Institute of Mental Health, Sir Colin Campbell Building, University of Nottingham Innovation Park, Triumph Road, Nottingham, NG7 2TU, UK. [email protected]. [email protected]. Editorial group: Cochrane Schizophrenia Group. Publication status and date: Edited (no change to conclusions), published in Issue 7, 2012. Review content assessed as up-to-date: 23 August 2006. Citation: Irving CB, Adams CE, Lawrie S. Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003082. DOI: 10.1002/14651858.CD003082.pub2. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Haloperidol was developed in the late 1950s for use in the field of anaesthesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. Objectives To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared to placebo. Search methods We initially electronically searched the databases of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane Schizophrenia Group’s Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH. We also checked references of all identified studies for further trial citations and contacted the authors of trials and pharmaceutical companies for further information and archive material. For the 2005 update we searched The Cochrane Library (2005, Issue 6). We updated this search 15 May 2012 and added the results to the awaiting classification section of the review. Selection criteria We included all relevant randomised controlled trials comparing the use of haloperidol (any oral dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). Our main outcomes of interest were death, loss to follow up, clinical and social response, relapse and severity of adverse effects. Data collection and analysis We evaluated data independently and analysed on an intention-to-treat basis, assuming that people who left the study early, or were lost to follow-up, had no improvement. Where possible and appropriate, we analysed dichotomous data using Relative Risk (RR) and calculated their 95% confidence intervals (CI). If appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was estimated. For continuous data, we calculated weighted mean differences. We excluded continuous data if loss to follow up was greater than 50% and inspected data for heterogeneity. Haloperidol versus placebo for schizophrenia (Review) 1 Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Main results Twenty-one trials randomising 1519 people are now included in this review. One new trial, Kane 2002 (n=414) has been added but it did not affect the overall results. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (3RCTs n=159, RR failing to produce a marked improvement 0.44 CI 0.3 to 0.6, NNT 3 CI 2 to 5). A further eight trials also found a difference favouring haloperidol across the 6-24 week period (8 RCTs n=308 RR no marked global improvement 0.68 CI 0.6 to 0.8 NNT 3 CI 2.5 to 5) but this may be an over estimate of effect as small negative studies were not identified. About half of those entering studies failed to complete the short trials, although, at 0-6 weeks, 11 studies found a difference that marginally favoured haloperidol (11 RCTs n=898, RR 0.8 CI 0.7 to 0.9, NNT 59 CI 38 to 200). Adverse effect data does, nevertheless, support clinical impression, that haloperidol is a potent cause of movement disorders, at least in the short term. Haloperidol promotes acute dystonia (3 RCTs n=93, RR 4.7 CI 1.7 to 44, NNH 5 CI 3 to 9), akathisia (4 RCTs n=333, RR 2.6 CI 1.4 to 4.8, NNH 7 CI 3 to 25) and parkinsonism (4 RCTs n=163, RR 11.7 CI 2.9 to 47, NNH 3 CI 2 to 5). Update search 2012: the 72 new citations in the awaiting classification section of the review may alter the results and conclusions of the review once assessed. Authors’ conclusions Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should not be a control drug of choice for randomised trials of new antipsychotics. PLAIN LANGUAGE SUMMARY Haloperidol versus placebo for schizophrenia Schizophrenia is a distressing and long-term mental illness affecting 1% of the population. Medication has been available since the 1950s and Haloperidol was one of the first antipsychotics to be offered. Despite the introduction of many other antipsychotics it is still very widely used, and it is the antipsychotic most often used to judge the effectiveness of new medications. This review aims to update the knowledge on the clinical trials comparing placebo and haloperidol. This review contains 21 studies involving a total of 1519 people who were either inpatients or living in the community. Haloperidol has been found to be better than placebo in improving general functioning and some symptoms in the short term (0-6 weeks), and just general functioning in the medium term (greater than six but less than 24 weeks). None of the people in any of these trials have been followed up for longer than 24 weeks. A significant number of people on haloperidol compared to those on placebo suffered from at least one adverse effect, mainly stiffness (dystonia) and movement disorders such as shaking or restlessness (Parkinsonism). In addition six trials containing 307 people found a significant number of people suffered from sleepiness compared to the control. Overall the data from these trials are not good, with many outcomes being presented in a way that does not allow them to be used in this review. Moreover just less than half of those taking haloperidol and slightly more than half of those receiving placebo left the studies early, suggesting that the design of the trial was possibly not acceptable to these participants. In the light of these results it is therefore somewhat surprising that this medication is used so widely as a comparison for new medication. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org) BACKGROUND 1992). Central to the treatment of this disabling mental illness are antipsychotic drugs, the earliest of which, chlorpromazine Schizophrenia affects about 1% of the world’s population irrespec- and haloperidol, were formulated and introduced in the 1950’s. tive of race, gender, social class or country of origin (Jablensky Haloperidol versus placebo for schizophrenia (Review) 2 Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. This introduction caused a revolution in the care of those with While an up-to-date systematic review of chlorpromazine has been serious mental illnesses (Dally 1967, Awad 1997). Despite the undertaken (Thornley 1998b) the use of haloperidol is currently formulation of a newer generation of atypical antipsychotics, based on traditional reviews that lack methods or quantification chlorpromazine and haloperidol are still the most frequently pre- (Ayd 1972, Ayd 1978, Settle