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Medically Unexplained Physical Symptoms, Anxiety, and Depression : A Meta-Analytic Review

Henningsen, Peter MD; Zimmermann, Thomas DiplPsych; Sattel, Heribert DiplPsych

doi: 10.1097/01.PSY.0000075977.90337.E7

Objective: Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior.

Methods: A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study.

Results: Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression.

Conclusions: Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as “common mental disorders” does not seem fully appropriate.

From the Department of Psychosomatic Medicine, University of Heidelberg, Heidelberg, Germany.

Address reprint requests to: Peter Henningsen, MD, Department of Psychosomatic Medicine, University Hospital, Thibautstrasse 2, 69115 Heidelberg, Germany. Email:

Received for publication June 6, 2002; revision received October 15, 2000.

This study was supported by a grant from the German Research Foundation (DFG He 3200/1-1). The authors thank Astrid Kristen for her help in procuring and indexing the literature.

Copyright © 2003 by American Psychosomatic Society
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