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Meta-Analysis
. 2024 Mar;44(1):267-271.
doi: 10.1002/npr2.12422. Epub 2024 Feb 6.

Antidepressants available in Japan for older people with major depressive disorder: A systematic review and meta-analysis

Taro Kishi  1 , Kenji Sakuma  1 , Masakazu Hatano  2 , Takenori Okumura  1 , Masaki Kato  3 , Hajime Baba  4   5 , Nakao Iwata  1
Affiliations
Meta-Analysis

Antidepressants available in Japan for older people with major depressive disorder: A systematic review and meta-analysis

Taro Kishi et al. Neuropsychopharmacol Rep. 2024 Mar.

Abstract

Aim: To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.

Methods: Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).

Results: Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.

Conclusions: Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.

Keywords: antidepressants available in Japan; efficacy; older people with major depressive disorder; safety; systematic review and meta-analysis.

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Conflict of interest statement

The authors have no specific conflicts of interest to declare concerning this study. They disclose the following interests that have arisen in the last 3 years: TK has received speaker's honoraria from Eisai, Janssen, Meiji, MSD, Otsuka, Sumitomo, Takeda, Mitsubishi‐Tanabe, Yoshitomi, Kyowa, and Viatris and research grants from Eisai, Grant‐in‐Aid for Scientific Research (19K08082 and 23K06998), Japan Agency for Medical Research and Development (JP22dk0307107, JP22wm0525024, JP23dk0307117, JP23wm0525024, and JP23dk0307122), and the Japanese Ministry of Health, Labour and Welfare (21GC1018). KS has received speaker's honoraria from Eisai, Janssen, Kyowa, Meiji, Otsuka, Sumitomo, and Takeda and research grants from Grant‐in‐Aid for Young Scientists (19K17099), Grant‐in‐Aid for Scientific Research © (23K06998), Fujita Health University School of Medicine Research Grant for Early‐Career Scientists, and Japan Agency for Medical Research and Development (JP22dk0307107). TO has received speaker's honoraria from Meiji, Kowa, Otsuka, Sumitomo, and Eisai. MH has received speaker's honoraria from Meiji, Sumitomo, and WELCIA, and Grant‐in‐Aid for Early‐Career Scientists (23K14827). MK received consulting fees from Sumitomo, Otsuka, Lundbeck, Takeda, and Shionogi; payment/honoraria from Sumitomo, Otsuka, Meiji, Eli Lilly, MSD, Pfizer, Janssen, Shionogi, Mitsubishi‐Tanabe, Takeda, Lundbeck, Viatris, Eisai, Kyowa, and Ono; and has received grant funding from the Japan Society for the Promotion of Science (22K07607), Japan Agency for Medical Research and Development (JP20dk0307081), SENSHIN Medical Research Foundation, the Japan Research Foundation for Clinical Pharmacology, and the Japanese Society of Clinical Neuropsychopharmacology. HB received grant funding from the Japan Society for the Promotion of Science and Esai and speaker's honoraria from Otsuka, Sumitomo, MSD, Meiji, Pfizer, Yoshitomi, Janssen, Kyowa, Mitsubishi‐Tanabe, Viatris, Takeda, Esai, Lundbeck, Mylan EPD, Mochida, Sawai, Kowa, Towa, and EA Pharma. NI has received speaker's honoraria from Eisai, Janssen, Meiji, Otsuka, Sumitomo, Takeda, Tanabe‐Mitsubishi, and Viatris and research grants from Daiichi Sankyo, Eisai, Meiji, Otsuka, Sumitomo, Takeda, and Mitsubishi‐Tanabe.

Figures

FIGURE 1
FIGURE 1
Forest plots. 1. Response rate; 2. Depression scale; 3. Remission rate; 4. Discontinuation due to AEs; At least one AE. 95% CI, 95% confidence interval; AD, antidepressant; AE, adverse event; DUL, duloxetine; ESC, escitalopram; IMI, imipramine; PLA, placebo; SER, sertraline; Std. Mean Differences, standardized mean difference; VEN, venlafaxine; VOR, vortioxetine.
See this image and copyright information in PMC

References

    1. Baba H, Kito S, Nukariya K, Takeshima M, Fujise N, Iga J, et al. Guidelines for diagnosis and treatment of depression in older adults: a report from the Japanese society of mood disorders. Psychiatry Clin Neurosci. 2022;76:222–234. - PubMed
    1. Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta‐analysis. Lancet. 2018;391:1357–1366. - PMC - PubMed
    1. Krause M, Gutsmiedl K, Bighelli I, Schneider‐Thoma J, Chaimani A, Leucht S. Efficacy and tolerability of pharmacological and non‐pharmacological interventions in older patients with major depressive disorder: a systematic review, pairwise and network meta‐analysis. Eur Neuropsychopharmacol. 2019;29:1003–1022. - PubMed
    1. Mallery L, MacLeod T, Allen M, McLean‐Veysey P, Rodney‐Cail N, Bezanson E, et al. Systematic review and meta‐analysis of second‐generation antidepressants for the treatment of older adults with depression: questionable benefit and considerations for frailty. BMC Geriatr. 2019;19:306. - PMC - PubMed
    1. Gutsmiedl K, Krause M, Bighelli I, Schneider‐Thoma J, Leucht S. How well do elderly patients with major depressive disorder respond to antidepressants: a systematic review and single‐group meta‐analysis. BMC Psychiatry. 2020;20:102. - PMC - PubMed

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