Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

898014.pdf (4.55 MB)

Document type

Article

Version

Accepted version

Publication date

2025-07-01

Publication license

cc-by-nc-nd (c) Elsevier B.V., 2025
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223837

Pharmacological treatments for atypical depression: A systematic review and network meta-analysis of randomized controlled trials

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.1016/j.euroneuro.2025.04.003

Abstract

Introduction: Atypical depression is a highly prevalent subtype that includes mood reactivity, hypersomnia, and leaden paralysis, necessitating different therapeutic approaches than melancholic depression. No network meta-analysis has been conducted on pharmacological treatments for atypical depression. Methods: We performed a PRISMA-compliant systematic review and network meta-analysis searching PubMed/Central, Clinicaltrials.gov, Embase, PsycINFO, Scopus, WebOfScience for randomized controlled trials (RCTs) testing pharmacological interventions for atypical depression until 04/24/24 (PROSPERO: CRD42024540262). Depressive symptom change (standardized mean difference/SMD), response, and all-cause discontinuation (acceptability) (risk ratio/RR) were co-primary outcomes; tolerability was the secondary outcome. Risk-of-bias and global/local inconsistencies were measured, and Confidence in Network Meta-Analysis (CINeMA) was used to assess the confidence in the evidence. Results: Out of 2214 hits, we included 21 eligible RCTs, 20 entering the NMA. For efficacy (k = 16, N = 903, treatments=12), only phenelzine outperformed placebo (SMD=-1.31, 95 %C.I.=[-2.14;-0.49]). Phenelzine, moclobemide, isocarboxazid, imipramine, selegiline, sertraline, and fluoxetine all outperformed nortriptyline (from SMD=-4.54, 95 %C.I.=[-8.02;-1.07] to SMD=-3.08, 95 %C.I.=[-5.42; -0.75]). Regarding response (k = 13, N = 1442, treatments=7), phenelzine (RR=2.58, 95 %C.I.=[2.02-3.31]), sertraline (RR=2.25, 95 %C.I.=[1.01-4.99]), moclobemide (RR=2.16, 95 %C.I.=[1.12-4.19]), fluoxetine (RR=1.89, 95 %C.I.=[1.30-2.76]) and imipramine (RR=1.76, 95 %C.I.=[1.35-2.28]) outperformed placebo, and phenelzine also outperformed imipramine (RR=1.56, 95 %C.I.=[1.25-1.96]). No treatment was significantly different from placebo for acceptability. No intervention outperformed placebo on any outcome in sensitivity analyses upon exclusion of high-risk-of-bias and intention-to-treat trials, likely due to a loss in power of the analysis, and overall CINeMA ratings were low/very low. Conclusions: Phenelzine might perform better than other compounds, but several drugs outperformed placebo in response. Nortriptyline performed worse than other treatments. High-quality studies are needed.

Subject

Depressió psíquica, Metaanàlisi, Intervenció psicològica, Antidepressius

Subject (English)

Mental depression, Meta-analysis, Psychological intervention, Antidepressants

Citation

Collections

Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citation

FORNARO, Michele, et al. Pharmacological treatments for atypical depression: A systematic review and network meta-analysis of randomized controlled trials. European Neuropsychopharmacology. 2025. Vol. 96, num. 46-57. ISSN 0924-977X. [consulted: 10 of August of 2026]. Available at: https://hdl.handle.net/2445/223837

Export metadata

JSON - METS

Share record