Haloperidol alone or in combination for the treatment of mania

Fifteen trials met the inclusion criteria and are included in the review. Interpretation of the results was hindered by the small total sample size and by the low quality of reporting of the included trials. There was some evidence that haloperidol was more efficacious than placebo in terms of reduction of manic and psychotic symptom scores, when used both as monotherapy and as add-on treatment to lithium or valproate. There is no evidence of difference in efficacy between haloperidol and risperidone, olanzapine, valproate, carbamazepine, sultopride and zuclopentixol. There was a statistically significant difference with haloperidol being probably less effective than aripiprazole. No comparative efficacy data with quetiapine, lithium or chlorpromazine were reported. Haloperidol caused more extrapyramidal symptoms (EPS) than placebo and more movement disorders and EPS but less weight gain than olanzapine. Haloperidol caused more EPS than valproate but no difference was found between haloperidol and lithium, carbamazepine, sultopride and risperidone in terms of side effects profile.

Authors' conclusions: 

There is some evidence that haloperidol is an effective treatment for acute mania. From the limited data available, there was no difference in overall efficacy of treatment between haloperidol and olanzapine or risperidone. Some evidence suggests that haloperidol could be less effective than aripiprazole. Referring to tolerability, when considering the poor evidence comparing drugs, clinicians and patients should consider different side effect profiles as an important issue to inform their choice.

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Background: 

The main objectives in treating mania are to control dangerous behaviour, reduce suicide, produce appropriate acute sedation and shorten the episode of mood disturbance. Among different drugs, haloperidol has for many years been used in treating psychotic patients, but it has a troublesome side effect profile.

Objectives: 

To assess the effects of haloperidol for the treatment of mania in comparison with placebo or other active drugs, either as monotherapy or add-on treatment.

Search strategy: 

We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (11 October 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL (1982-2003), PsycINFO (1872-2003) and reference lists. We also contacted experts, triallists and pharmaceutical companies in the field.

Selection criteria: 

Randomised trials comparing haloperidol with placebo or other active treatment in the treatment of acute manic or mixed episodes in patients with bipolar disorder or schizoaffective disorder.

Data collection and analysis: 

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.

Main results: 

Fifteen trials involving 2022 people were included. Compared to placebo, haloperidol was more effective at reducing manic symptoms, both as monotherapy (Weighted Mean Difference (WMD) -5.85, 95% Confidence Interval (CI) -7.69 to -4.00) and as adjunctive treatment to lithium or valproate (WMD -5.20, 95% CI -9.26 to -1.14). There was a statistically significant difference, with haloperidol being less effective than aripiprazole (Relative Risk (RR) 1.45, 95% CI 1.22 to 1.73). No significant differences between haloperidol and risperidone, olanzapine, carbamazepine or valproate were found. Compared with placebo, a statistically significant difference in favour of haloperidol in failure to complete treatment (RR 0.74, 95% Cl 0.57 to 0.96) was reported. Haloperidol was associated with less weight gain than olanzapine (RR: 0.28, 95% CI 0.12 to 0.67), but with a higher incidence of tremor (RR: 3.01, 95% CI 1.55 to 5.84) and other movement disorders.

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