Stubhaug, Bjarte, Lie, Stein Atle, Ursin, Holger et al. · The British journal of psychiatry : the journal of mental science · 2008 · DOI
This study tested whether a structured talk therapy program (cognitive-behavioural therapy) and/or a medication called mirtazapine could help people with chronic fatigue. Seventy-two patients were divided into groups receiving either the therapy program, the medication, or a placebo (fake pill). The therapy program worked best in the first 12 weeks, but when patients combined therapy first with medication afterward, they showed the most improvement by week 24.
This study provides evidence that a combination approach—specifically therapy followed by medication—may be more effective than either treatment alone for chronic fatigue. Understanding optimal treatment sequencing and the potential value of multimodal interventions is important for developing better management strategies for ME/CFS patients.
This study does not establish that these treatments cure chronic fatigue or work equally well in all patient populations. The relatively small sample size (n=72), short follow-up period (24 weeks), and focus on a specialist clinic population limit generalizability. The mechanisms underlying why sequence matters remain unclear from this data alone.
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
Stubhaug, Bjarte, Lie, Stein Atle, Ursin, Holger, & Eriksen, Hege R (2008). Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial.. The British journal of psychiatry : the journal of mental science. https://doi.org/10.1192/bjp.bp.106.031815
BibTeX
@article{mecfsatlas-stubhaug-2008-cognitive-behavioural,
author = {Stubhaug, Bjarte and Lie, Stein Atle and Ursin, Holger and Eriksen, Hege R},
title = {Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial.},
journal = {The British journal of psychiatry : the journal of mental science},
year = {2008},
doi = {10.1192/bjp.bp.106.031815},
note = {PubMed: 18310583},
url = {https://www.mecfsatlas.com/evidence/stubhaug-2008-cognitive-behavioural},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/stubhaug-2008-cognitive-behavioural
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