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Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis
Galling, Britta1,2,3; Roldan, Alexandra4; Hagi, Katsuhiko2,5; Rietschel, Liz6; Walyzada, Frozan2; Zheng, Wei7; Cao, Xiao-Lan8; Xiang, Yu-Tao9; Zink, Mathias10; Kane, John M.2,3,11,12; Nielsen, Jimmi13,14; Leucht, Stefan15; Correll, Christoph U.2,3,11,12
Source PublicationWORLD PSYCHIATRY

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.

KeywordAntipsychotics Polypharmacy Augmentation Monotherapy Schizophrenia Clozapine Aripiprazole
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Indexed BySCI ; SSCI ; SSCI
WOS Research AreaPsychiatry
WOS SubjectPsychiatry
WOS IDWOS:000393863000019
The Source to ArticleWOS
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Cited Times [WOS]:46   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Department of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Charité-Universitätsmedizin 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 Universität München, Munich, Germany
Recommended Citation
GB/T 7714
Galling, Britta,Roldan, Alexandra,Hagi, Katsuhiko,et al. Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis[J]. WORLD PSYCHIATRY,2017,16(1):77-89.
APA Galling, Britta.,Roldan, Alexandra.,Hagi, Katsuhiko.,Rietschel, Liz.,Walyzada, Frozan.,...&Correll, Christoph U..(2017).Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis.WORLD PSYCHIATRY,16(1),77-89.
MLA Galling, Britta,et al."Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis".WORLD PSYCHIATRY 16.1(2017):77-89.
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