Haloperidol discontinuation for people with schizophrenia

Schizophrenia is a disabling serious mental illness that can be chronic. Haloperidol, one of the first generation of antipsychotic drugs, is effective in the treatment of schizophrenia but can have adverse side effects. The effects of stopping haloperidol in people with schizophrenia who are stable on their prescription are not well researched in the context of systematic reviews.

To review the effects of haloperidol discontinuation in people with schizophrenia who are stable on haloperidol.

On 20 February 2015, 24 May 2017, and 12 January 2019, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers.

We included clinical trials randomising adults with schizophrenia or related disorders who were receiving haloperidol, and were stable. We included trials that randomised such participants to either continue their current treatment with haloperidol or discontinue their haloperidol treatment. We included trials that met our selection criteria and reported usable data.

We independently checked all records retrieved from the search and obtained full reports of relevant records for closer inspection. We extracted data from included studies independently. All usable data were dichotomous, and we calculated relative risks (RR) and their 95% confidence intervals (95% CI) using a fixed-effect model. We assessed risk of bias within the included studies and used GRADE to create a 'Summary of findings' table.

We included five randomised controlled trials (RCTs) with 232 participants comparing haloperidol discontinuation with haloperidol continuation. Discontinuation was achieved in all five studies by replacing haloperidol with placebo. The trials' size ranged between 23 and 87 participants. The methods of randomisation, allocation concealment and blinding were poorly reported.Participants allocated to discontinuing haloperidol treatment were more likely to show no improvement in global state compared with those in the haloperidol continuation group (n = 49; 1 RCT; RR 2.06, 95% CI 1.33 to 3.20; very low quality evidence: our confidence in the effect estimate is limited due to relevant methodological shortcomings of included trials). Those who continued haloperidol treatment were less likely to experience a relapse compared to people who discontinued taking haloperidol (n = 165; 4 RCTs; RR 1.80, 95% CI 1.18 to 2.74; very low quality evidence). Satisfaction with treatment (measured as numbers leaving the study early) was similar between groups (n = 43; 1 RCT; RR 0.13, 95% CI 0.01 to 2.28; very low quality evidence).No usable mental state, general functioning, general behaviour or adverse effect data were reported by any of the trials.

This review provides limited evidence derived from small, short-term studies. The longest study was for one year, making it difficult to generalise the results to a life-long disorder. Very low quality evidence shows that discontinuation of haloperidol is associated with an increased risk of relapse and a reduction in the risk of 'global state improvement'. However, participant satisfaction with haloperidol treatment was not different from participant satisfaction with haloperidol discontinuation as measured by leaving the studies early. Due to the very low quality of these results, firm conclusions cannot be made. In addition, the available studies did not report usable data regarding the adverse effects of haloperidol treatment.Considering that haloperidol is one of the most widely used antipsychotic drugs, it was surprising that only a small number of studies into the benefit and harm of haloperidol discontinuation were available. Moreover, the available studies did not report on outcomes that are important to clinicians and to people with schizophrenia, particularly adverse effects and social outcomes. Better designed trials are warranted.