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Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment

Authors
 Ta-Chuan Yeh  ;  Christoph U Correll  ;  Fu-Chi Yang  ;  Mu-Hong Chen  ;  Ping-Tao Tseng  ;  Chih-Wei Hsu  ;  Andre F Carvalho  ;  Brendon Stubbs  ;  Trevor Thompson  ;  Che-Sheng Chu  ;  Chia-Ling Yu  ;  Jae Il Shin  ;  Szu-Nian Yang  ;  Yu-Kang Tu  ;  Chih-Sung Liang 
Citation
 ASIAN JOURNAL OF PSYCHIATRY, Vol.79 : 103375, 2023-01 
Journal Title
ASIAN JOURNAL OF PSYCHIATRY
ISSN
 1876-2018 
Issue Date
2023-01
MeSH
Antipsychotic Agents* / therapeutic use ; Clozapine* / therapeutic use ; Entropy ; Humans ; Memantine ; Mirtazapine / pharmacology ; Mirtazapine / therapeutic use ; Network Meta-Analysis ; Schizophrenia* / drug therapy
Keywords
Antipsychotic agent ; Electroconvulsive therapy ; Psychotropic drug ; Schizophrenia ; Transcranial magnetic stimulation
Abstract
Objective: To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS). Methods: Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking. Results: We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (−4.41; −5.61, −3.21), electroconvulsive therapy (ECT) (−4.32; −5.43, −3.21), and memantine (−2.02; −3.14, −0.91) were ranked as the best three treatments. For positive symptoms, ECT (−5.18; −5.86, −4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (−3.38; −4.50, −2.26), duloxetine (−3.27; −4.25, −2.29), and mirtazapine (−1.73; −2.71, −0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl D-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93). Conclusion: Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.) © 2022 Elsevier B.V.
Full Text
https://www.sciencedirect.com/science/article/pii/S1876201822003732
DOI
10.1016/j.ajp.2022.103375
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197891
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