Abstract: Twenty-five trials randomising 4651 people are now included in this review. We chose seven main outcomes of interest for the 'Summary of findings' table. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (4 RCTs n = 472, RR 0.67 CI 0.56 to 0.80, moderate quality evidence). A further eight trials also found a difference favouring haloperidol across the six weeks to six months period (8 RCTs n = 307 RR 0.67 CI 0.58 to 0.78, moderate quality evidence). Relapse data from two trials favoured haloperidol at < 52 weeks but the evidence was very low quality (2 RCTs n = 70, RR 0.69 CI 0.55 to 0.86). Moderate quality evidence showed about half of those entering studies failed to complete the short trials (six weeks to six months), although, at up to six weeks, 16 studies found a difference that marginally favoured haloperidol (n = 1812, RR 0.87 CI 0.80 to 0.95). Adverse effect data does, nevertheless, support clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Moderate quality evidence indicates that haloperidol caused parkinsonism (5 RCTs n = 485, RR 5.48 CI 2.68 to 11.22), akathisia (6 RCTs n = 695, RR 3.66 CI 2.24 to 5.97, and acute dystonia (5 RCTs n = 471, RR 11.49 CI 3.23 to 10.85). Discharge from hospital was equivocal between groups (1 RCT n = 33, RR 0.85 CI 0.47 to 1.52, very low quality evidence). Data were not reported for death and patient satisfaction. 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 be less favoured as a control drug for randomised trials of new antipsychotics.

Plain-language summary: The aim of this review was to evaluate the effects of haloperidol for schizophrenia and other similar serious mental illnesses compared with ‘dummy’ or no treatment (placebo). A new search for trials was carried out in May 2012 and the review now includes 25 studies with a total of 4651 people. Review authors rated the quality of evidence reported in the trials for seven main outcomes (global state, death, discharge from hospital, relapse, leaving the study early, adverse effects and satisfaction with treatment). For global state, leaving the study early and adverse effects the reviewers rated the evidence as moderate quality, however, relapse and discharge from hospital were rated to be very low quality evidence. There were no data available for death and satisfaction with treatment. Based on moderate quality evidence, haloperidol was found to be better than placebo in treating schizophrenia. More people given haloperidol improved in the first six weeks of treatment than those given placebo. However, a significant number of people on haloperidol suffered from side effects, including muscle stiffness, uncontrollable shaking, tremors, sleepiness and restlessness. Authors concluded that haloperidol is a potent and effective antipsychotic for treating the symptoms of schizophrenia but has the potential to cause debilitating side effects. People with schizophrenia and psychiatrists may wish to prescribe a newer antipsychotic drug with fewer side effects. Finally, a large proportion of other information and data in the trials were poor and badly reported, meaning that better studies are required. Many people, from both groups left the trials early. This suggests that the design and running of the trials was poor and perhaps not acceptable to people. In light of these findings, it is perhaps surprising that haloperidol is a benchmark antipsychotic in widespread use for treating schizophrenia. It is also surprising that haloperidol is widely used as a comparison for new medication. Haloperidol is an effective antipsychotic drug but has serious and debilitating side effects. Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness.