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Meta-Analysis
. 2014 Jul 9;2014(7):CD009268.
doi: 10.1002/14651858.CD009268.pub2.

Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia

Magdolna Tardy  1 , Maximilian Huhn, Werner Kissling, Rolf R Engel, Stefan Leucht
Affiliations
Meta-Analysis

Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia

Magdolna Tardy et al. Cochrane Database Syst Rev. .

Abstract

Background: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds, however, low-potency antipsychotic drugs are often clinically perceived as less efficacious than high-potency compounds, and they also seem to differ in their side-effects.

Objectives: To review the effects in clinical response of haloperidol and low-potency antipsychotics for people with schizophrenia.

Search methods: We searched the Cochrane Schizophrenia Group Trials Register (July 2010).

Selection criteria: We included all randomised trials comparing haloperidol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis.

Data collection and analysis: We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model.

Main results: The review currently includes 17 randomised trials and 877 participants. The size of the included studies was between 16 and 109 participants. All studies were short-term with a study length between two and 12 weeks. Overall, sequence generation, allocation procedures and blinding were poorly reported. We found no clear evidence that haloperidol was superior to low-potency antipsychotic drugs in terms of clinical response (haloperidol 40%, low-potency drug 36%, 14 RCTs, n = 574, RR 1.11, CI 0.86 to 1.44 lowquality evidence). There was also no clear evidence of benefit for either group in acceptability of treatment with equivocal difference in the number of participants leaving the studies early due to any reason (haloperidol 13%, low-potency antipsychotics 17%, 11 RCTs, n = 408, RR 0.82, CI 0.38 to 1.77, low quality evidence). Similar equivocal results were found between groups for experiencing at least one adverse effect (haloperidol 70%, low-potency antipsychotics 35%, 5 RCTs n = 158, RR 1.97, CI 0.69 to 5.66, very low quality evidence ). More participants from the low-potency drug group experienced sedation (haloperidol 14%, low-potency antipsychotics 41%, 2 RCTs, n = 44, RR 0.30, CI 0.11 to 0.82, moderate quality evidence), orthostasis problems (haloperidol 25%, low-potency antipsychotics 71%, 1 RCT, n = 41, RR 0.35, CI 0.16 to 0.78) and weight gain (haloperidol 5%, low-potency antipsychotics 29%, 3 RCTs, n = 88, RR 0.22, CI 0.06 to 0.81). In contrast, the outcome 'at least one movement disorder' was more frequent in the haloperidol group (haloperidol 72%, low-potency antipsychotics 41%, 5 RCTs, n = 170, RR 1.64, CI 1.22 to 2.21, low quality evidence). No data were available for death or quality of life. The results of the primary outcome were robust in several subgroup and sensitivity analyses.

Authors' conclusions: The results do not clearly show a superiority in efficacy of haloperidol compared with low-potency antipsychotics. Differences in adverse events were found for movement disorders, which were more frequent in the haloperidol group, and orthostatic problems, sedation and weight gain, which were more frequent in the low-potency antipsychotic group. The quality of studies was low, and the quality of evidence for the main outcomes of interest varied from moderate to very low, so more newer studies would be needed in order to draw a definite conclusion about whether or not haloperidol is superior or inferior to low-potency antipsychotics.

PubMed Disclaimer

Conflict of interest statement

Magdolna Tardy ‐ none to declare. Maximilian Huhn ‐ none to declare. Werner Kissling ‐ has received speaker and/or advisory board/consultancy honoraria from Janssen, Sanofi‐Aventis, Johnson and Johnson, Pfizer, Bayer, BMS, Astra Zeneca, Lundbeck, Novartis and EliLilly. Rolf Engel ‐ none to declare. Stefan Leucht ‐ has received honoraria for lectures from Abbvie, Astra Zeneca, BristolMyersSquibb, ICON, EliLilly, Janssen, Johnson & Johnson, Roche, SanofiAventis, Lundbeck and Pfizer; honoraria for consulting/advisory boards from Roche, EliLilly, Medavante, BristolMyersSquibb, Alkermes, Janssen, Johnson & Johnson and Lundbeck. EliLilly has provided medication for a study with SL as primary investigator.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, outcome: 1.1 Response to treatment.
1.1
1.1. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 1 Response to treatment.
1.2
1.2. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 2 Mental state: 1a. General ‐ overall symptoms ‐ average endpoint score/change (BPRS, high = poor).
1.3
1.3. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 3 Mental state: 1b. General ‐ overall symptoms ‐ average endpoint score/change (PANSS, high = poor).
1.4
1.4. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 4 Global state: Average endpoint score/change (CGI, high = poor).
1.5
1.5. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 5 Relapse.
1.6
1.6. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 6 Leaving the study early.
1.7
1.7. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 7 Adverse effects: 1. General ‐ at least one adverse effect.
1.8
1.8. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 8 Adverse effects: 2a. Specific ‐ movement disorders.
1.9
1.9. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 9 Adverse effects: 2b. Specific ‐ movement disorders ‐ average endpoint score/change (ESRS, high = poor).
1.10
1.10. Analysis
Comparison 1 Comparison 1: HALOPERIDOL versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 10 Adverse effects: 3. Others.
2.1
2.1. Analysis
Comparison 2 Subgroup analysis, Outcome 1 Response to treatment ‐ each low‐potency antipsychotic separately.
2.2
2.2. Analysis
Comparison 2 Subgroup analysis, Outcome 2 Response to treatment ‐ treatment resistance.
3.1
3.1. Analysis
Comparison 3 Sensitivity analysis, Outcome 1 Response to treatment ‐ fixed‐effect model.
3.2
3.2. Analysis
Comparison 3 Sensitivity analysis, Outcome 2 Response to treatment ‐ exclusion of studies in which randomisation was assumed from blinding.
3.3
3.3. Analysis
Comparison 3 Sensitivity analysis, Outcome 3 Response to treatment ‐ exclusion of non double‐blind studies.
3.4
3.4. Analysis
Comparison 3 Sensitivity analysis, Outcome 4 Response to treatment ‐ exclusion of outlier study leading to heterogeneity (Dufresne 1993).
See this image and copyright information in PMC

Comment in

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