Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: A systematic review and meta-analysis
Introduction
Second-generation antipsychotics (SGA) are commonly used in the treatment of patients with schizophrenia (Diabetes Expert Group, 2004, Leucht et al., 2009) and have even become the drugs of choice in some countries, such as the United States. However, there are substantial concerns about the metabolic side effects of SGAs. In general, today there is significant agreement on the importance of the metabolic side effects, such as changes in body weight, glucose utilization, or lipid status, unrecognized or unknown at the beginning of the introduction of SGAs (Meyer, 2002). For some physicians these side effects are the most important as they might predispose to type 2 diabetes mellitus and cardiovascular disease (Meyer et al., 2008a, Daumit et al., 2008), while others may weigh them against other side effects such as extrapyramidal side effects or sexual problems.
The metabolic side effects have become an issue in competitive advertising between pharmaceutical companies, thus causing a polarization. Randomized controlled trials (RCTs) are probably the most bias free way to compare such side effects. There is a substantial amount of research in this field, however, currently there is no meta-analysis comparing the metabolic side effects of the SGAs head-to-head.
We therefore conducted a meta-analysis of studies directly comparing the following SGAs to one another: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine. This article is focusing on the metabolic side-effects of second-generation antipsychotics while the data on the efficacy of these medications have been published elsewhere (Leucht et al., 2009).
Section snippets
Search strategy
The register of the Cochrane Schizophrenia Group (CSG) was searched for randomized, blinded trials comparing orally administered second-generation antipsychotics (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine) head-to-head in the treatment of schizophrenia or related disorder (schizoaffective, schizophreniform, or delusional disorder) without language restrictions. The search terms used were all possible 36 combinations of the names
The search (for QUOROM flow diagram (Moher et al., 1999) see Fig. 1)
The search strategy identified 3750 citations. Of these, 3119 abstracts were excluded because they were clearly not relevant. 631 articles were ordered for more detailed evaluation and 321 of these were excluded. 310 publications on 90 studies were included; however, only 48 studies with 105 relevant arms reported usable data on at least one of the outcomes cholesterol, glucose or weight. Of these 48 studies, 6 studies included amisulpride, 5 aripiprazole, 11 clozapine, 37 olanzapine, 11
Discussion
We present the first head-to-head meta-analysis of the metabolic side effects of second-generation antipsychotics in randomized controlled trials, showing three similar clusters for the three outcomes with olanzapine and clozapine showing the most elevation of weight, cholesterol, and glucose. Quetiapine, risperidone, and sertindole had intermediate elevations. Aripiprazole and amisulpride displayed intermediate or low elevations and ziprasidone the lowest elevations.
We found that olanzapine
Role of the Funding Source
Financial support was provided by a grant from the Technische Universität München (HWP II) (CR), the German Federal Ministry of Education and Research, no FKZ: 01KG 0606, GZ: GFKG01100506 (SL); and a grant from the National Institute of Mental Health, Advanced Center for Intervention and Services Research Center (MH-68580), Grant No. 1 P01MH68580-01 CFDA #93.242, the Maryland Psychiatric Research Center (JD). The funding source had no involvement in study design, collection, analysis and
Contributors
CRK, KK and SL contributed to designing the study, data extraction, statistical analysis, and writing the report. SS, HH, FS and CAS contributed to data extraction and writing of the report. WK and JD contributed to designing the study and writing the report. All authors contributed to and have approved the final manuscript.
Conflict of interest
Christine Rummel-Kluge has received speaker honoraria or travel grants to attend scientific meetings from AstraZeneca, Janssen-Cilag, EliLilly and Pfizer.
Stefan Leucht has received speaker and/or consultancy honoraria from SanofiAventis, BMS, EliLilly, Janssen/Johnson and Johnson, Lundbeck and Pfizer; and he has received funding for research projects from EliLilly and SanofiAventis.
Werner Kissling has received speaker or consultancy honoraria from SanofiAventis, BMS, Lilly, Janssen, Lundbeck,
Acknowledgement
We thank the following authors and pharmaceutical companies for providing additional information on their studies: D. Addington, I. Bitter, R. Conley, D. Daniel, L. De Haan, S. Dollfus, O. Fleurot, H. Heinrich, T. Hwang, D. Jeste, W. Kadus, J. Kane, R. Keefe, D. Kelly, M. Krakowski, M. Kluge, Y. Liu, S. McGurk, K. Mori, A. Mortimer, D. Naber, H. Ozguven, J. Peuskens, B. Quednow, Q. Ren, M. Riedel, N. Schooler, D. Sechter, J. Švestka, J. Volavka, M. Wagner, K. Zhong, AstraZeneca, EliLilly,
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