TY - JOUR
T1 - Recurrence of Mania or Depression among Adult Bipolar Patients Who Continued Using Lithium
T2 - A Single-group Summary Meta-Analysis of Randomized Trials
AU - Kishi, Taro
AU - Sakuma, Kenji
AU - Okuya, Makoto
AU - Matsuda, Yuki
AU - Esumi, Satoru
AU - Hashimoto, Yasuhiko
AU - Hatano, Masakazu
AU - Miyake, Nobumi
AU - Miura, Itaru
AU - Miyahara, Kengo
AU - Fujita, Kiyoshi
AU - Kawashima, Kunihiro
AU - Mishima, Kazuo
AU - Iwata, Nakao
N1 - Funding Information:
T.K. received speaker's honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, Mochida, MSD, and Tanabe-Mitsubishi (Yoshitomi), as well as research grants from the Japanese Ministry of Health, Labour and Welfare (H29-Seishin-Ippan-001, 19GC1012), Grant-in-Aid for Scientific Research (C), and Fujita Health University School of Medicine. K.S. has received speaker's honoraria from Eisai, Kissei, Meiji, Otsuka, and Torii and has received a Fujita Health University School of Medicine research grant, as well as a Grant-in-Aid for Young Scientists (B). M.O. has received speaker's honoraria from Meiji. Y.M. has received speaker's honoraria from Dainippon Sumitomo, Janssen, Kyowa, Otsuka, Tanabe-Mitsubishi, and Yoshitomi. S.E. received speaker's honoraria from Eisai and Towa, as well as research grants from the JSPS KAKENHI Grants for Encouragement of Scientists. Y.H. has no conflicts of interest with any company. M.H. received speaker's honoraria from Dainippon Sumitomo and Otsuka. N.M. received speaker's honoraria from Dainippon Sumitomo and Meiji. I.M. received speaker's honoraria from Daiichi Sankyo, Dainippon Sumitomo, Janssen, Meiji Seika Pharma, Mochida, MSD, Mylan, Otsuka, Pfizer, Takeda, Tanabe-Mitsubishi, and Yoshitomi. K.M. has no conflicts of interest with any company. K.F. received speaker's honoraria from Otsuka, Dainippon Sumitomo, Janssen, Kyowa, and Meiji. K.K. received speaker's honoraria from Eisai, Meiji, Dainippon Sumitomo, Otsuka, Tanabe-Mitsubishi and Yoshitomi. K.M. received research support from the Japanese Ministry of Health, Labour and Welfare (H29-Seishin-Ippan-001, 19GC1012) and the Japanese Ministry of Education, Culture, Sports, Science and Technology Collaborative research fund with Taisho; as well as speaker's honoraria from Eisai, MSD, Takeda, Astellas, Pfizer, Otsuka, Mochida, Mitsubishi Tanabe, Yoshitomi, and Janssen; and research grants from Eisai, Nobelpharma, Otsuka, and Takeda. N.I. has received speaker's honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer as well as research grants from Eisai, Takeda, Dainippon Sumitomo, and Otsuka.
Funding Information:
Funding source: The present study was supported by the Health and Labor Sciences Research Grants (H29-Seishin-Ippan-001, 19GC1012).
Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background The exact recurrence rate of bipolar disorder in patients receiving lithium maintenance phase treatment and the modifiers associated with recurrence are still unknown. Methods We searched Embase, PubMed, and CENTRAL from inception until April 28, 2020. Outcomes included recurrence rate of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes; all-cause discontinuation rate; and discontinuation rate due to adverse events. A random-effects model, single-group summary meta-Analysis was conducted. A meta-regression analysis to examine whether the modifiers (total number of patients, %female, mean age, duration of study, duration of preliminary phase, publication year, bipolar disorder type, mood status at recruitment, presence of a placebo arm, sponsorship, enrichment design, number of treatment arms, and risk of bias for blinding or randomization) were associated with the event rate of the outcomes was also performed. Results We identified 21 randomized trials (n = 1,415; mean study duration, 78.40 ± 32.10 weeks; %female, 54.85%; mean age, 43.47 ± 4.88 years). The event rates (95% confidence interval [CI]) were as follows: recurrence of any mood episode, 39.8% (32.8%, 47.1%); depressive episodes, 25.6% (18.8%, 34.0%); manic/hypomanic/mixed episodes, 18.5% (13.7%, 24.7%); all-cause discontinuation rate, 67.0% (57.2%, 75.5%); and discontinuation rate due to adverse events, 8.7% (5.1%, 14.7%). After adjusting for multiple testing, our meta-regression analysis showed association only between the all-cause discontinuation rate and presence of a placebo arm. Conclusions The recurrence rate of depressive episodes seemed to be higher than the recurrence rate of manic/hypomanic/mixed episodes. The all-cause discontinuation rate was high. However, the studies included in our meta-Analysis were of short duration.
AB - Background The exact recurrence rate of bipolar disorder in patients receiving lithium maintenance phase treatment and the modifiers associated with recurrence are still unknown. Methods We searched Embase, PubMed, and CENTRAL from inception until April 28, 2020. Outcomes included recurrence rate of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes; all-cause discontinuation rate; and discontinuation rate due to adverse events. A random-effects model, single-group summary meta-Analysis was conducted. A meta-regression analysis to examine whether the modifiers (total number of patients, %female, mean age, duration of study, duration of preliminary phase, publication year, bipolar disorder type, mood status at recruitment, presence of a placebo arm, sponsorship, enrichment design, number of treatment arms, and risk of bias for blinding or randomization) were associated with the event rate of the outcomes was also performed. Results We identified 21 randomized trials (n = 1,415; mean study duration, 78.40 ± 32.10 weeks; %female, 54.85%; mean age, 43.47 ± 4.88 years). The event rates (95% confidence interval [CI]) were as follows: recurrence of any mood episode, 39.8% (32.8%, 47.1%); depressive episodes, 25.6% (18.8%, 34.0%); manic/hypomanic/mixed episodes, 18.5% (13.7%, 24.7%); all-cause discontinuation rate, 67.0% (57.2%, 75.5%); and discontinuation rate due to adverse events, 8.7% (5.1%, 14.7%). After adjusting for multiple testing, our meta-regression analysis showed association only between the all-cause discontinuation rate and presence of a placebo arm. Conclusions The recurrence rate of depressive episodes seemed to be higher than the recurrence rate of manic/hypomanic/mixed episodes. The all-cause discontinuation rate was high. However, the studies included in our meta-Analysis were of short duration.
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U2 - 10.1097/JCP.0000000000001264
DO - 10.1097/JCP.0000000000001264
M3 - Article
C2 - 32701902
AN - SCOPUS:85090048704
VL - 40
SP - 468
EP - 474
JO - Journal of Clinical Psychopharmacology
JF - Journal of Clinical Psychopharmacology
SN - 0271-0749
IS - 5
ER -