Gracious, B, Wisner, K L · Biological psychiatry · 1991 · DOI
This study tested whether a medication called nortriptyline (an older type of antidepressant) could help one person with ME/CFS. The researchers gave the patient either the medication or a placebo (inactive pill) without telling them which was which, and tracked how they felt. This type of single-patient study can provide useful information, but it only shows what happened with one individual and cannot prove the treatment works for everyone with ME/CFS.
ME/CFS patients often experience depression and pain alongside fatigue, so understanding whether medications like nortriptyline could help is clinically relevant. Well-designed single-patient studies can sometimes reveal treatment effects before larger trials are undertaken, and this carefully controlled approach helps avoid bias from patient expectations.
This single case study cannot prove nortriptyline is effective for ME/CFS patients generally—results from one person do not establish whether the medication helps most patients or any other patient. The study does not address whether any observed changes were due to the medication itself, placebo effect, natural disease fluctuation, or other factors. It cannot determine safe or appropriate dosing across the ME/CFS population.
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
Gracious, B & Wisner, K L (1991). Nortriptyline in chronic fatigue syndrome: a double blind, placebo-controlled single case study.. Biological psychiatry. https://doi.org/10.1016/0006-3223(91)90297-y
BibTeX
@article{mecfsatlas-gracious-1991-nortriptyline-chronic,
author = {Gracious, B and Wisner, K L},
title = {Nortriptyline in chronic fatigue syndrome: a double blind, placebo-controlled single case study.},
journal = {Biological psychiatry},
year = {1991},
doi = {10.1016/0006-3223(91)90297-y},
note = {PubMed: 1912132},
url = {https://www.mecfsatlas.com/evidence/gracious-1991-nortriptyline-chronic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/gracious-1991-nortriptyline-chronic
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