Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review,meta‐analysis and meta‐regression analysis |
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| Authors: | Britta Galling Alexandra Roldán Katsuhiko Hagi Liz Rietschel Frozan Walyzada Wei Zheng Xiao‐Lan Cao Yu‐Tao Xiang Mathias Zink John M Kane Jimmi Nielsen Stefan Leucht Christoph U Correll |
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| Institution: | 1. Department of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Charité-Universit?tsmedizin Berlin, Berlin, Germany;2. Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA;3. Hofstra Northwell School of Medicine, Hempstead, NY, USA;4. Department of Psychiatry, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain;5. Sumitomo Dainippon Pharma Co., Tokyo, Japan;6. University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland;7. Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;8. Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China;9. Unit of Psychiatry, Faculty of Health Sciences, University of Macao, Taipa, Macao, SAR, China;10. Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;11. Feinstein Institute for Medical Research, Manhasset, NY, USA;12. Albert Einstein College of Medicine, Bronx, NY, USA;13. Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark;14. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;15. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universit?t München, Munich, Germany |
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| Abstract: | Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta‐analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co‐primary outcomes were total symptom reduction and study‐defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=–0.53, 95% CI: ?0.87 to ?0.19, p=0.002). However, superiority was only apparent in open‐label and low‐quality trials (both p<0.001), but not in double‐blind and high‐quality ones (p=0.120 and 0.226, respectively). Study‐defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non‐significant in double‐blind and high‐quality studies (both p=0.990). Findings were replicated in clozapine and non‐clozapine augmentation studies. No differences emerged regarding all‐cause/specific‐cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=–0.38, 95% CI: ?0.63 to ?0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=–0.41, 95% CI: ?0.79 to ?0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double‐blind/high‐quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation. |
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| Keywords: | Antipsychotics polypharmacy augmentation monotherapy schizophrenia clozapine aripiprazole |
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