Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis.
- Galling B Department of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- Roldán A Department of Psychiatry, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
- Hagi K Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA.
- Rietschel L University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
- Walyzada F Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA.
- Zheng W Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
- Cao XL Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China.
- Xiang YT Unit of Psychiatry, Faculty of Health Sciences, University of Macao, Taipa, Macao, SAR, China.
- Zink M Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Kane JM Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA.
- Nielsen J Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark.
- Leucht S Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München, Munich, Germany.
- Correll CU Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA.
- 2017-01-28
Published in:
- World psychiatry : official journal of the World Psychiatric Association (WPA). - 2017
English
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.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1002/wps.20387
- PMID 28127934
- Persistent URL
- https://sonar.ch/global/documents/89786
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