Agger, Johanne L, Schröder, Andreas, Gormsen, Lise K et al. · The lancet. Psychiatry · 2017 · DOI
This study tested whether a low-dose antidepressant called imipramine could help people who have multiple overlapping chronic conditions like ME/CFS and irritable bowel syndrome. Over 10 weeks, patients taking imipramine were more likely to report feeling better (53%) compared to those taking placebo (25%), but imipramine caused more side effects, particularly moderate ones like dry mouth and dizziness.
This study is important because many ME/CFS patients have multiple overlapping functional somatic syndromes and lack evidence-based treatment options. The finding that imipramine shows modest efficacy with an acceptable side-effect profile in this comorbid population provides clinicians with a potential pharmacological option to discuss with appropriately selected patients.
This study does not prove that imipramine works specifically for ME/CFS alone, as participants had multiple syndromes and the mechanism of improvement remains unclear. It also does not establish long-term efficacy beyond 10 weeks, nor does it show that improvement was driven by antidepressant action on mood rather than other neurobiological effects. The study excludes patients with concurrent depression or anxiety, so results may not apply to the substantial subset of ME/CFS patients with comorbid psychiatric conditions.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Agger, Johanne L, Schröder, Andreas, Gormsen, Lise K, Jensen, Jens S, Jensen, Troels S, & Fink, Per K (2017). Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study.. The lancet. Psychiatry. https://doi.org/10.1016/S2215-0366(17)30126-8
BibTeX
@article{mecfsatlas-agger-2017-imipramine-versus,
author = {Agger, Johanne L and Schröder, Andreas and Gormsen, Lise K and Jensen, Jens S and Jensen, Troels S and Fink, Per K},
title = {Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study.},
journal = {The lancet. Psychiatry},
year = {2017},
doi = {10.1016/S2215-0366(17)30126-8},
note = {PubMed: 28408193},
url = {https://www.mecfsatlas.com/evidence/agger-2017-imipramine-versus},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/agger-2017-imipramine-versus
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