Hall, K T, Kossowsky, J, Oberlander, T F et al. · The pharmacogenomics journal · 2016 · DOI
This study tested whether a blood pressure medication called clonidine helps people with ME/CFS, and found that it worked differently depending on patients' genes. Specifically, people with a certain genetic variation in a gene called COMT had worse outcomes (fewer steps walked, worse sleep, lower quality of life) when taking clonidine, while those with a different version of the gene showed no improvement or worsening. This suggests that genetic testing might help doctors figure out which patients should avoid this medication.
This study provides evidence that one-size-fits-all treatment approaches may not work for ME/CFS, and that genetic testing could help personalize care. Understanding how genetic variation affects medication response is crucial for developing safer, more effective treatment strategies and avoiding medications that might harm certain patients. These findings highlight the biological heterogeneity of ME/CFS and support precision medicine approaches.
This study does not prove that clonidine causes harm in all ME/CFS patients—only in those with a specific genetic variant. It cannot establish whether COMT genetic variation causes differences in clonidine metabolism or response, only that an association exists. The findings are limited to adolescents and may not apply to adults or other populations. Additionally, this is a candidate gene study, not a genome-wide investigation, so other genetic factors may be equally important.
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
Hall, K T, Kossowsky, J, Oberlander, T F, Kaptchuk, T J, Saul, J P, Wyller, V B, et al. (2016). Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.. The pharmacogenomics journal. https://doi.org/10.1038/tpj.2016.53
BibTeX
@article{mecfsatlas-hall-2016-genetic-variation,
author = {Hall, K T and Kossowsky, J and Oberlander, T F and Kaptchuk, T J and Saul, J P and Wyller, V B and Fagermoen, E and Sulheim, D and Gjerstad, J and Winger, A and Mukamal, K J},
title = {Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.},
journal = {The pharmacogenomics journal},
year = {2016},
doi = {10.1038/tpj.2016.53},
note = {PubMed: 27457818},
url = {https://www.mecfsatlas.com/evidence/hall-2016-genetic-variation},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/hall-2016-genetic-variation
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