Unexplained Fatigue May be Depression…

Dr. Shawn Talbott (Ph.D., CNS, LDN, FACSM, FACN, FAIS) has gone from triathlon struggler to gut-brain guru! With a Ph.D. in Nutritional Biochemistry, he's on a mission to boost everyday human performance through the power of natural solutions and the gut-brain axis.

Feelings of tiredness – especially for no apparent reason – is one of the most common complaints that stressed out patients make to their doctors.
A recent meta-analysis (see abstract below) found that depression was the most common cause of fatigue (almost 20% of cases). This analysis looked at 26 studies covering nearly 15,000 patients with tiredness as a primary or secondary symptom (including fatigue, weariness, lethargy, malaise, feeling knackered, run down, and in need of a tonic).
The researchers concluded that clinicians looking for causes of unexplained fatigue should focus on depression and psychosocial problems.
Thanks for reading,
Shawn M Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN
Nutritional Biochemist and Author


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BMC Fam Pract. 2016 Oct 20;17(1):147.

The differential diagnosis of tiredness: a systematic review.

Author information

  • 1Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany. Rebekka.Stadje@t-online.de.
  • 2Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.



Tiredness is one of the most frequent complaints in primary care. Although often self-limiting and frequently associated with psychosocial stress, patients but also their physicians are often uncertain regarding a serious cause and appropriate diagnostic work-up. We conducted a systematic review and meta-analysis of studies reporting on differential diagnosis of fatigue in primary care.


MEDLINE, EMBASE and conference abstracts were searched for primary care based studies of patients presenting with tiredness. Twenty-six studies were included. We report on anaemia, malignancy, serious organic disease, depression and the chronic fatigue syndrome (CFS) as causes of tiredness as presenting complaint.


We found considerable heterogeneity of estimates which was reduced by limiting our analysis to high quality studies. Prevalences were as follows-anaemia: 2.8 % (CI (confidence interval) 1.6-4.8 %); malignancy: 0.6 % (CI 0.3-1.3 %); serious somatic disease: 4.3 % (CI 2.7-6.7 %); depression 18.5 % (CI 16.2-21.0 %). Pooling was not appropriate for CFS. In studies with control groups of patients without the symptom of tiredness, prevalence of somatic disease was identical to those complaining of tiredness. Depression, however, was more frequent among those with tiredness.


Serious somatic disease is rare in patients complaining of tiredness. Since prevalence is similar in patients without tiredness, the association may not be causal. Extensive investigations are only warranted in case of specific findings from the history or clinical examination. Instead, attention should focus on depression and psychosocial problems.

KEYWORDS: Fatigue; Meta-analysis; Primary care; Tiredness

PMID: 27765009


PMCID: PMC5072300


DOI: 10.1186/s12875-016-0545-5
About the Author

Exercise physiologist (MS, UMass Amherst) and Nutritional Biochemist (PhD, Rutgers) who studies how lifestyle influences our biochemistry, psychology and behavior - which kind of makes me a "Psycho-Nutritionist"?!?!

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