TY - JOUR
T1 - Effects of Discontinuation of Drugs Used for Augmentation Therapy on Treatment Outcomes in Depression
T2 - A Systematic Review and Meta-analysis
AU - Kato, Hideo
AU - Koizumi, Teruki
AU - Takeuchi, Hiroyoshi
AU - Tani, Hideaki
AU - Mimura, Masaru
AU - Uchida, Hiroyuki
N1 - Funding Information:
H. K. has nothing to declare. T. K. has nothing to declare. H. Tak. has received research grants from Japan Society for the Promotion of Science (JSPS), Japan Agency for Medical Research and Development (AMED), SENSHIN Medical Research Foundation, and Novartis Pharma; Fellowship grants from Astellas Foundation for Research on Metabolic Disorders, the Canadian Institutes of Health Research (CIHR), Centre for Addiction and Mental Health (CAMH) Foundation, and the Japanese Society of Clinical Neuropsychopharmacology (JSCNP); Speaker’s fees from Kyowa, Janssen, Meiji Seika Pharma, Mochida, Otsuka, Sumitomo
Funding Information:
Sumitomo Dainippon Pharma. H. Tan. has received grants from Eli Lilly, the Japanese Society of Clinical Neuropsychopharmacology, and Canadian Insitutes of Health Research; manuscript or speaker’s fees from Otsuka, Sumitomo Dainippon Pharma, Wiley, and Yoshitomi Yakuhin. M. M. has received grants or consultant fees from Eisai, Astellas Pharma, GlaxoSmithKline, and Meiji, and received speaker’s honoraria from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji, Otsuka Pharmaceutical, Pfizer, and Yoshitomi Yakuhin within the past 3 years. H. U. has received grants from Eisai, Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, and Meiji-Seika Pharmaceutical; speaker’s honoraria from Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, Eisai, and Meiji-Seika Pharma; and advisory panel payments from Dainippon-Sumitomo Pharma within the past 3 years.
Publisher Copyright:
© 2020. Thieme. All rights reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Introduction There has been no consensus on whether and how long add-on drugs for augmentation therapy should be continued in the treatment of depression. Methods Double-blind randomized controlled trials that examined the effects of discontinuation of drugs used for augmentation on treatment outcomes in patients with depression were identified. Meta-analyses were performed to compare rates of study withdrawal due to any reason, study-defined relapse, and adverse events between patients who continued augmentation therapy and those who discontinued it. Results Seven studies were included (n=841 for continuing augmentation therapy; n=831 for discontinuing augmentation therapy). The rate of study withdrawal due to any reason was not significantly different between the 2 groups (risk ratio [RR]=0.86, 95% confidence interval [CI]=0.69-1.08, p=0.20). Study withdrawal due to relapse was less frequent in the continuation group than in the discontinuation group (RR=0.61, 95% CI=0.40-0.92, p=0.02); however, this statistical significance disappeared when one study using esketamine as augmentation was excluded. Analysis of the data from 5 studies that included a stabilization period before randomization found less frequent relapse in the continuation group than in the discontinuation group (RR=0.47, 95% CI=0.36-0.60, p<0.01). This finding was repeated when the esketamine study was excluded. Discussion No firm conclusions could be drawn in light of the small number of studies included. Currently available evidence suggests that add-on drugs, other than esketamine, used for augmentation therapy for depression may be discontinued. This may not be the case for patients who are maintained with augmentation therapy after remission.
AB - Introduction There has been no consensus on whether and how long add-on drugs for augmentation therapy should be continued in the treatment of depression. Methods Double-blind randomized controlled trials that examined the effects of discontinuation of drugs used for augmentation on treatment outcomes in patients with depression were identified. Meta-analyses were performed to compare rates of study withdrawal due to any reason, study-defined relapse, and adverse events between patients who continued augmentation therapy and those who discontinued it. Results Seven studies were included (n=841 for continuing augmentation therapy; n=831 for discontinuing augmentation therapy). The rate of study withdrawal due to any reason was not significantly different between the 2 groups (risk ratio [RR]=0.86, 95% confidence interval [CI]=0.69-1.08, p=0.20). Study withdrawal due to relapse was less frequent in the continuation group than in the discontinuation group (RR=0.61, 95% CI=0.40-0.92, p=0.02); however, this statistical significance disappeared when one study using esketamine as augmentation was excluded. Analysis of the data from 5 studies that included a stabilization period before randomization found less frequent relapse in the continuation group than in the discontinuation group (RR=0.47, 95% CI=0.36-0.60, p<0.01). This finding was repeated when the esketamine study was excluded. Discussion No firm conclusions could be drawn in light of the small number of studies included. Currently available evidence suggests that add-on drugs, other than esketamine, used for augmentation therapy for depression may be discontinued. This may not be the case for patients who are maintained with augmentation therapy after remission.
KW - antidepressant
KW - augmentation
KW - depression
KW - ketamine
KW - relapse
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U2 - 10.1055/a-1330-8587
DO - 10.1055/a-1330-8587
M3 - Article
C2 - 33368090
AN - SCOPUS:85098695731
VL - 54
SP - 106
EP - 116
JO - Pharmakopsychiatrie und Neuropsychopharmakologie
JF - Pharmakopsychiatrie und Neuropsychopharmakologie
SN - 0176-3679
IS - 3
ER -