Are all first-generation antipsychotics equally effective in treating schizophrenia? A meta-analysis of randomised, haloperidol-controlled trials

Abstract

Objectives: Narrative, unsystematic reviews revealed no differences in efficacy between the various first-generation antipsychotics (FGAs) resulting in the psychopharmacological assumption of comparable efficacy between the different FGAs. We sought to determine if the assumption of comparable efficacy of all FGAs can be regarded as evidence-based using meta-analytic statistics. Methods: A systematic literature survey (Cochrane Schizophrenia Group trial register) was applied to identify all RCTs that compared oral haloperidol with another oral FGA in schizophrenia. Primary outcome was dichotomous treatment response. Secondary outcomes were symptom severity measured by rating scales, discontinuation rates, and specific adverse effects. Results: Altogether, 79 RCTs with 4343 participants published between 1962 and 1999 were included. We found a significant between-group difference only between haloperidol and nemonapride, but not for the remaining 19 investigated FGAs. There were no significant differences for discontinuation rates. Conclusions: As most of the single meta-analytic comparisons can be regarded as underpowered, the evidence for the assumption of comparable efficacy of all FGAs is inconclusive. We therefore cannot confirm or reject the statements of previous narrative, unsystematic reviews in this regard. Our findings were limited by the small sample size in the individual comparisons and the low methodological quality in many included studies.

Key words:

• Schizophrenia
• antipsychotics
• haloperidol
• meta-analysis
• effect sizes

Acknowledgments

This research was supported by grant FKZ: 01KG1026 from the German Federal Ministry of Education and Research to S. Leucht. We thank the editorial team of the Cochrane Schizophrenia Group for the support that enables the elaboration of this meta-analysis. The Group produces and maintains standard texts for the use in the methods sections of their reviews. The present article is based on the literature search conducted for two Cochrane reviews published in the Cochrane Database of Systematic Reviews (CDSR): (1) Dold M, Samara MT, Li C, Tardy M, Leucht S. 2015. Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. Cochrane Database Syst Rev:CD009831; and (2) Tardy M, Huhn M, Kissling W, Engel RR, Leucht S. 2014. Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev:CD009268. Furthermore, we would like to thank Professor Nedopil for providing further information on his trial.

Statement of interest

M. Dold has received a travel grant from Janssen-Cilag. S. Kasper has received grant/research support from Bristol Myers-Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Organon, Pfizer, Sepracor, and Servier; he has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Merck Sharp and Dome (MSD), Novartis, Organon, Pfizer, Schwabe, Sepracor, and Servier; and he has served on speakers’ bureaus for Angelini, AOP-Pharma, AstraZeneca, Bristol Myers-Squibb, Eli Lilly, Janssen, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe, Sepracor, Servier, and Wyeth. In the last 3 years, S. Leucht has received lecture honoraria from Eli Lilly, Lundbeck, Pfizer, Janssen, BMS, Janssen, Johnson and Johnson, Lundbeck, Roche, SanofiAventis, ICON, and Abbvie; he has served as a consultant for Roche, Janssen, Lundbeck, and Eli Lilly. He has prepared educational material and publications for the Lundbeck Institute and Roche. Eli Lilly has provided medication for a clinical trial led by S. Leucht as principal investigator. All other authors declare that they have no conflicts of interest.