Académique Documents
Professionnel Documents
Culture Documents
Lancet 2007; 369: 94655 Although functional somatic syndromes (FSS) show substantial overlap, treatment research is mostly conned to
Published Online single syndromes, with a lack of valid and generally accepted diagnostic criteria across medical specialties. Here, we
February 6, 2007 review management for the full variety of FSS, drawn from systematic reviews and meta-analyses since 2001, and give
DOI:10.1016/S0140-
6736(07)60159-7
recommendations for a stepped care approach that dierentiates between uncomplicated and complicated FSS.
Non-pharmacological treatments involving active participation of patients, such as exercise and psychotherapy, seem
Department of Psychosomatic
Medicine and Psychotherapy, to be more eective than those that involve passive physical measures, including injections and operations.
University Hospital, Technical Pharmacological agents with CNS action seem to be more consistently eective than drugs aiming at restoration of
University of Munich, peripheral physiological dysfunction. A balance between biomedical, organ-oriented, and cognitive interpersonal
Langerstrasse 3,
approaches is most appropriate at this truly psychosomatic interface. In view of the iatrogenic component in the
81675 Munich, Germany
(P Henningsen MD); maintenance of FSS, doctor-centred interventions and close observation of the doctorpatient relationship are of
Department of Psychosomatic particular importance.
Medicine and Psychotherapy,
University Hospital, University
of Tuebingen, Germany
Introduction sensation); and complaints centring around fatigue and
(S Zipfel MD); and Department Functional somatic syndromes (FSS) are common exhaustion. The name of single FSS typically signies
of Psychosomatic and General worldwide and in practically all areas of medicine. FSS are the current lead symptoms, but denitions usually
Clinical Medicine, University a burden for suerers, they are also often dicult to treat include other bodily complaints as well, and some FSS
Hospital, University of
Heidelberg, Germany
for doctors and costly for society.13 Diagnostic and are named not according to the lead symptoms, but
(W Herzog MD) therapeutic approaches to FSS vary substantially across according to the implied cause.
Correspondence to: and within medical specialties, from biomedicine to There is no objective criterion to decide whether a
Prof Peter Henningsen psychology. In this review, we try to improve the under- pattern of bodily complaints should be seen as a functional
p.henningsen@tum.de standing of common factors across single FSS and hence somatic syndrome or as indicator of a medically explained
of common therapeutic strategies across medical disease or as something else, and lists drawn up by
specialities. We give an overview of current concepts under- dierent authors reect their particular backgrounds and
lying the management of FSS, of results of appropriate views. For instance, some reviewers concentrate more on
therapeutic trials in single syndromes and diagnostic FSS that are disputed, such as multiple chemical
analogues, and of practical steps for management. sensitivity,2 others emphasise those that are common and
undisputed in dierent branches of somatic medicine,
Denition, overlap, terminology, and such as chronic pelvic pain, and some also include single
classication symptoms, such as dizziness or tinnitus. Three syndromes
FSS are characterised by patterns of persistent bodily are mentioned more regularly than others: irritable bowel
complaints for which adequate examination does not syndrome, chronic fatigue syndrome, and bromyalgia,
reveal suciently explanatory structural or other specied probably because of the existence of well dened and
pathology. We dierentiate three main types of bodily popular research diagnostic criteria. The list of FSS
complaints in FSS: pain of dierent location (back, head, (table 1) is subject to change, as some fall out of use2 and
muscles or joints, abdomen, chest, etc); functional new syndromes are proposed almost every year.7,8
disturbance in dierent organ systems (eg, palpitation, Functional disturbances of voluntary movement and of
dizziness, constipation or diarrhoea, movement, sensation, so-called pseudoneurological symptoms, and
chronic low-back pain share the essential clinical features
of FSS and should be counted with them.4,9
Search strategy and selection criteria The delineation of FSS from disease with clear
We searched the Cochrane Library, MEDLINE , and PSYCINFO from 2001. We used a string structural pathology is problematic in clinical assessments
of search terms previously applied in a meta-analysis on FSS and diagnostic analogues and in research with structured diagnostic interviews.
and adapted it to the terms of FSS that are indicated in table 1. We included commonly However, an increasing number of bodily complaints is a
referenced and highly regarded publications from before 2001. We also searched the strong indicator of a non-organic nature,10 and for
reference lists of articles identied by this search strategy and selected those we judged assessment of the whole pattern of bodily complaints, a
relevant. For the section on therapeutic evidence we restrict presentation of search results systematic chart review achieves very good reliability
to systematic reviews and meta-analyses published since 2001. Reviews had to dene a between raters for the distinction of documented
comprehensive search strategy and quality evaluation of primary studies and present structural organic disease, documented non-organic
results in a systematic way. Whereas some of these reviews cover all aspects of treatment disease, and minor acute illness.11
of single FSS, others concentrate on particular treatment components for single FSS or Prevalence of some FSS like irritable bowel syndrome
across dierent types of medically unexplained symptoms. We did not include systematic reaches up to 15%,12 but reliable prevalence rates are
reviews on particular treatments not focused on FSS or diagnostic analogues. dependent on established research diagnostic criteria,
which exist for only a few FSS. Small variations in the
02%, it is 9% for chronic unexplained fatigue.13 For Chronic fatigue syndrome (CFS) 5
some syndromes, the published prevalence rates are also Fibromyalgia (FMS) 5
inuenced by the special interests of supporters of the Multiple chemical sensitivity 4
respective concept of FSS.14 Nonspecic chest pain 4
Premenstrual syndrome 3
Overlap of single FSS Non-ulcer dyspepsia 3
Many clinicians and researchers who focus on one specic Repetitive strain injury 3
FSS have the impression that it occurs in isolated form. Tension headache 3
Conceptually, however, the bodily symptoms used as Temporomandibular joint disorder 3
diagnostic criteria (ie, abdominal pain or fatigue) are not Atypical facial pain 3
specic but overlap for many FSS. Many patients full Hyperventilation syndrome 2
criteria for more than one syndrome. The extent of this Globus syndrome 2
empirical overlap between single FSS is from around 10% Sick building syndrome 2
in the general population to over 50% in clinic Chronic pelvic pain 2
populations.1,1518 Furthermore, multiple studies have Chronic whiplash syndrome 2
shown high self-reported scores of other unexplained Chronic lyme disease 2
bodily symptoms in dierent FSS, including pseudo- Silicone breast implant eects 2
neurological symptoms19 and chronic low-back pain.20 Candidiosis hypersensitivity 2
Common characteristics of FSS, in addition to the pattern Food allergy 2
of bodily complaints, are female preponderance18 and Gulf War syndrome 2
signicant overlap with anxiety and depression, which is Mitral valve prolapse 2
higher in FSS than in comparable, organically explained Hypoglycaemia 2
diseases (ie, irritable bowel syndrom vs inammatory Chronic low back pain 2
bowel disease or bromyalgia vs rheumatoid arthritis); Dizziness 2
however, many cases of FSS also occur without anxiety or Interstitial cystitits 1
depression. This association therefore neither can be seen Tinnitus 1
as an unspecic psychological reaction to the presence of Pseudoseizures 1
bodily complaints nor as masked or somatised depression
Insomnia 1
or anxiety alone.21 Further common features of FSS are the
substantial eect on quality of life, which is commonly as Table 1: Number of reviews in which individual FSS are mentioned1,2,46
large as in comparable diseases of clear organic origin,10,22
and the response to interventions that primarily inuence encourage a narrow or splitting view by the respective
the function of the CNS by behavioural, psychotherapeutic, specialist on the current main bodily symptom and
or psychopharmacological means. symptomatic treatment only; in addition, most of them
Taken together, the balancing of research and therapeutic give no indication of symptom severity. In parallel, there
practice between a splitting and a lumping view of FSS is is the possibility to classify organically unexplained bodily
a clinical and conceptual challenge,23,24 and this is related symptoms as mental disorders: in chapter V of ICD 10,
to the ongoing debate whether FSS should be classied as and in the Diagnostic and Statistical Manual, they are
a physical or mental disorder, or whether a truly psycho- classied as somatoform disorders, with somatisation
somatic third-way is possible. disorder as the rare, most serious prototype used for
patients with multiple symptoms over time. This type of
Terminology and classication classication encourages a lumping perspective (ie, to
Currently, no term or classication is fully satisfactory look at the whole pattern of current and previous bodily
when dealing with the clinical phenomenon of patients symptoms and also at psychological and behavioural
reporting persistent bodily complaints for which no clear characteristics of the patient). However, this perspective
organic reason can be found. The term medically historically implied a psychogenic origin of FSS that is
unexplained symptoms is not adequate because of the not only problematic from a scientic point of view, but
diculties in dening insucient explanation and also also oensive for patients who want to avoid being seen
because it implies that explanations that involve as mentally ill.
psychosocial or cultural factors are not part of medicine. Debates about future editions of the classications for
Many of the terms used for single FSS are classied in the mental disorders range from the contested suggestion to
dierent medical sections of International Classication of abolish the category somatoform disorders altogether to
Diseases 10th Revision (ICD 10). They generally have good the suggestion to introduce a category of general-
acceptance by patients and medical specialists, but they medicinepsychiatry interface disorders.2528 From a
Biofeedback ++67
Strength training ++67
Chronic fatigue syndrome Immmunoglobulin + 72,73
Antidepressants + 61,72,73
CBT +++61,64,7274
Interferon 73 Aerobic exercise +++61,64,7275
Corticosteroids 72,73
Non-ulcer dyspepsia Proton pump inhibitors ++76 .. Psychotherapy ++81 .. ..
Helicobacter pylori eradication ++77,78
H2-Receptor agonists ++76,79,80
Prokinetics +76,80
Antacids 76
Tension headache Botulinum toxin +82 Tricyclic antidepressants Behavioural therapy +++86 Spinal manipulation 8790 Acupuncture +91
+++84,85
Niacin83 SSRI ++84,85 Physiotherapy 90
Non-specic chest pain .. .. Psychological interventions ++ 74,92
.. ..
Chronic pelvic pain Progestogen Sertraline 93 Counselling and ultrasound Adhesiolysis 93 ..
scanning +93
Goserelin +93 Multidisciplinary treatment +93 Uterine nerve ablation 93 ..
Manual techniques 94
Premenstrual syndrome Progesterone/progestogen 95 SSRI +++97 .. .. Complementary or
alternative therapies 98
GnRHa +++96 .. ..
Temporomandibular joint Analgesics 99 Tricyclic .. Splint therapy 100,101 ..
disorder antidepressants +99
Environmental illness or .. .. CBT for electromagnetic Screen lters or shields 102 Selenium for environmental
electromagnetic hypersensitivity ++102 illness 103
hypersensitivity
Chronic low-back pain Nonsteroidal anti-inammatory Tricyclic and tetracyclic CBT +++104,107 Radiofrequency Acupuncture +104,117,118
drugs +++104 antidepressants +++104106 denervation +104,111,112
Muscle relaxants ++104 SSRI 105 Multidisciplinary treatment +++104,108 Prolotherapy 104,113
Opioid analgesics ++104 Exercise therapy ++104,109 Transcutaneous electrical
nerve stimulation 104,114,115
Back schools ++104,110 Spinal manipulation +104,116
Diagnostic analogues .. .. CBT for SD or MUS ++ 64,74
.. Consultation letter to doctor
(MUS, SD, CD) for SD or MUS ++74
Hypnosis for CD +74,119
Paradoxical intention for CD +119
IBS=irritable bowel syndrome (C=constipation, D=diarrhoea). NSAID=non-steroidal anti-inammarory drug. SSRI=selective serotonin reuptake inhibitors. SNRI=selective serotonin and norepinephrine reuptake
inhibitor. GnRHa=gonadotrophin releasing hormone analogue. CBT=cognitive behavioural therapy. MUS=multiple unexplained physical symptoms. SD=somatoform disorders. CD=conversion disorder. +++=strong
evidence; ++=moderate evidence; +=weak evidence; =no evidence for ecacy of treatment. This table does not list all treatments with weak or no evidence dealt with in the systematic reviews. For simplicity,
strength of evidence for ecacy of a specic treatment type is indicated in four dierent grades, with the reviews contributing to this summary estimate. 23 Cochrane reviews are included.51,59,66,70,7577,81,84,91,93,97,101,107110,112,11
3,115,116,118,119
For such an integration of systematic reviews, which use dierent criteria and represent dierent opinions in heterogeneous clinical elds, estimation of eect sizes was not feasible. The table shows general
empirical trends in the management of functional somatic syndromes; it is not an adequate basis for individual treatment recommendations. The terms used in the table were taken from the systematic reviews and
vary in grade of dierentiation (eg, for some FSS the reviews state the evidence for psychotherapy, whereas for others they state the evidence for dierent forms of psychotherapy separately).
action and active behavioural interventions are eective, noteworthy as the weak to moderate eect of hormones
whereas peripheral drugs and passive physical inter- and counselling with reassuring ultrasound scanning.
ventions show only weak or no evidence for ecacy.
Premenstrual syndrome, temporomandibular disorder, and
Chronic fatigue syndrome environmental illness
Few studies have been added to the therapy research The therapeutic evidence as reported in systematic
literature on chronic fatigue syndrome since 2001. The two reviews is very limited for these syndromes. For temporo-
treatments with best evidence for ecacy since the 1990s mandibular joint disorder, there has recently been an
are graded exercise and cognitive behavioural therapy, upsurge of interest in the role of somatisation and its
whereas there is little evidence to support the use of combination with organic joint ndings.28
antidepressants and dierent immunological and steroidal
drugs. In one systematic review,72 around 130 dierent Chronic low-back pain
outcome measures were identied in 44 studies, thus The evidence for treatments of chronic low-back pain is
limiting the generalisability of the ndings broader than for most other syndromes, with nine
dierent Cochrane reviews and a large systematic review
Non-ulcer dyspepsia initiated by the European commission attesting to this.
The evidence for peripheral drugs is best for proton-pump Treatments with active involvement (in the form of
inhibitors. Evidence for others is weaker, with many psychotherapy or exercise or other) and drugs with a
contradicting studies and systematic reviews from the central rather than peripheral mode of action seem to be
past122 currently distilled into evidence for a consistent
but limited eect of proton-pump inhibitors, H2-receptor
Panel 2: Management recommendations for FSS
agonists, and prokinetics and of Helicobacter pylori
eradication in infected patients. Antidepressants have Assessment
not been tested rigorously in this type of functional Think of the possibility of FSS in patients with enduring physical symptoms; do not
gastrointestinal disorder. All four studies on psycho- equate them with malingering
therapy showed positive eects for dierent types of Be attentive to clues of the patient indicating bodily or emotional distress beyond the
psychotherapy each, but interpretation is limited by small current lead symptom and outside your specialist eld
sample sizes and adjustments for dierences between Assess functioning, patient expectations, and illness behaviour
intervention and control groups. Avoid repetitive investigations only to calm the patient or yourself
Decide whether patient has uncomplicated single FSS or complicated FSS. Are there
Tension headache bodily or mental symptoms clearly beyond single FSS? Is there excessive loss of
Behavioural psychotherapies and tricyclic antidepressants functioning? Is there dysfunctional expectations or illness behaviour?
seem to have the best treatment eects in patients with Dierential stepped care
tension headache. Patients given acupuncture improved Step 1a: uncomplicated FSS
relative to waiting-list controls, but this intervention is Reassurance with positive explanation of FSS; do not only convey negative test results
probably no more eective than minimum or sham acu- Symptomatic measures like pain relief
puncture. Botulinum toxin, although showing promise Advise graded activation or exercise rather than rest
in open trials, shows contradictory results in randomised
controlled trials.123 Step 1b: complicated FSS
Measures as in step 1a for current main symptom
Non-specic chest pain Consider antidepressant treatment
The only systematic reviews we could identify were of Advise on dysfunctional attributions and illness behaviour and encourage reframing
psychological interventions for which there is moderate of symptoms within biopsychosocial framework (ie, incorporate both the patients
evidence of ecacy. This syndrome refers to chest pain beliefs about the organic nature of their symptoms and how these can be aected by a
but no evidence of underlying coronary, gastrointestinal, range of psychological and contextual factors)
or other organic pathology, therefore it is more exclusive If appropriate: appointments at regular intervals rather than patient-initiated
than the category non-cardiac chest pain. For the latter, Step 2: if either step 1a or step 1b prove to be insucient
there is some indication that typical gastrointestinal Prepare referral to psychotherapist or mental-health specialist with reappointment
drugs, such as proton-pump inhibitors, are eective.124 Ensure that traumatic stressors and maintaining context factors, such as litigation, are
assessed
Chronic pelvic pain Continue with appointments at regular intervals rather than patient-initiated
The term is used dierently by gynaecologists and Liaise with psychotherapist or mental-health specialist on further treatment planning
urologists. The former see it as dierent from FSS with and diculties
primarily urological symptoms,93 whereas the latter use it Step 3: If step 2 proves insucient and if appropriate in your country
as superordinate category with subcategories like interstitial Multidisciplinary treatment including symptomatic measures, activating
cystitis and chronic prostatitis.125 In terms of treatment physiotherapy, and psychotherapy
ecacy, the lack of eect of surgical procedures is as
The management of FSS will most likely continue to be 20 Pincus T, Burton AK, Vogel S, Field AP. A systematic review of
psychological factors as predictors of chronicity/disability in
an important health-care focus on all levels of care. Its prospective cohorts of low back pain. Spine 2002; 27: E10920.
future outlook will reect the state of integration, the 21 Henningsen P, Zimmermann T, Sattel H. Medically unexplained
dierent elds of general and specialist somatic as well as physical symptoms, anxiety, and depression: a meta-analytic review.
psychological medicine will achieve. Competent communi- Psychosom Med 2003; 65: 52833.
22 Ferrari R, Kwan O. The no-fault avor of disability syndromes.
cation, between the elds of medicine as well as between Med Hypotheses 2001; 56: 7784.
doctors and patients, will be a mainstay in this endeavour. 23 Wessely S, White PD. There is only one functional somatic
Contributors syndrome. Brit J Psychiatry 2004; 185: 9596.
All authors contributed equally to the preparation and writing of this review. 24 Cho HJ, Skowera A, Cleare A, Wessely S. Chronic fatigue
syndrome: an update focusing on phenomenology and
Conict of interest statement pathophysiology. Curr Opin Psychiatry 2006; 19: 6773.
We declare that we have no conict of interest. 25 Mayou R, Kirmayer LJ, Simon G, Kroenke K, Sharpe M.
Somatoform disorders: time for a new approach in DSM-V.
Acknowledgments
Am J Psychiatry 2005; 162: 84755.
We are grateful to Heribert Sattel for help with the literature search and
26 Rief W, Henningsen P, Hiller W. Classication of somatoform
to Bernd Lwe for valuable support. We are also indebted to Paul Enck
disorders (letter). Am J Psychiatry 2006; 163: 74647.
and three anonymous reviewers for comments on an earlier draft.
27 Strassnig M, Stowell KR, First MB, Pincus HA. General medical
Supported in part by DFG (PISO) and BMBF (Funktional).
and psychiatric perspectives on somatoform disorders: separated by
References an uncommon language. Curr Opin Psychiatry 2006; 19: 194200.
1 Wessely S, Nimnuan C, Sharpe M. Functional somatic syndromes: 28 Henningsen P, Loewe B. Depression, pain and somatoform
one or many? Lancet 1999; 354: 93639. disorders. Curr Opin Psychiatry 2006; 19: 1924.
2 Barsky AJ, Borus JF. Functional somatic syndromes. 29 Saito YA, Petersen GM, Locke GR 3rd, Talley NJ. The genetics of
Ann Intern Med 1999; 130: 91021. irritable bowel syndrome. Clin Gastroenterol Hepatol 2005; 3: 105765.
3 Barsky AJ, Orav EJ, Bates DW. Somatization increases medical 30 Sullivan PF, Evengard B, Jacks A, Pedersen NL. Twin analyses of
utilization and costs independent of psychiatric and medical chronic fatigue in a Swedish national sample. Psychol Med 2005; 35:
comorbidity. Arch Gen Psychiatry 2005; 62: 90310. 132736.
4 Mayou R, Farmer A. Abc of psychological medicine: functional 31 Fiddler M, Jackson J, Kapur N, Wells A, Creed F. Childhood
somatic symptoms and syndromes. BMJ 2002; 325: 26568. adversity and frequent medical consultations. Gen Hosp Psychiatry
5 Escobar JI, Hoyos-Nervi C, Gara M. Medically unexplained physical 2004; 26: 36777.
symptoms in medical practice: a psychiatric perspective. 32 Hotopf M. Preventing somatization. Psychol Med 2004; 34: 19598.
Environ Health Perspect 2002; 110 (suppl 4): 63136. 33 Waller E, Scheidt CE, Hartmann A. Attachment representation and
6 Manu P. Functional somatic syndromes. Cambridge: Cambridge illness behavior in somatoform disorders. J Nerv Ment Dis 2004;
University Press 1999. 192: 20009.
7 Perme B, Ranjith G, Mohan R, Chandrasekaran R. Dhat (semen 34 Wilkinson SR. Coping and Complaining: Attachment and the
loss) syndrome: a functional somatic syndrome of the Indian Language of Dis-Ease. London: Brunner and Routledge, 2003.
subcontinent? Gen Hosp Psychiatry 2005; 27: 21517. 35 Bass C, Murphy M. Somatoform and personality disorders:
8 Patel V, Pednekar S, Weiss H, et al. Why do women complain of syndromal comorbidity and overlapping developmental pathways.
vaginal discharge? A population survey of infectious and J Psychosom Res 1995; 39: 40327.
pyschosocial risk factors in a south Asian community. 36 White PD, Thomas JM, Kangro HO, et al. Predictions and
Int J Epidemiol 2005; 34: 85362. associations of fatigue syndromes and mood disorders that occur
9 Reuber M, Mitchell AJ, Howlett SJ, Crimlisk HL, Grnewald RA. after infectious mononucleosis. Lancet 2001; 358: 194654.
Functional symptoms in neurology: questions and answers. 37 Spiller R, Campbell E. Post-infectious irritable bowel syndrome.
J Neurol Neurosurg Psychiatry 2005; 76: 30714. Curr Opin Gastroenterol 2006; 22: 1317.
10 Kroenke K, Spitzer RL, Williams JB, et al. Physical symptoms in 38 Ferrari R, Russell AS, Carroll LJ, Cassidy JD. A re-examination of
primary care: predictors of psychiatric disorders and functional the whiplash associated disorders (WAD) as a systemic illness.
impairment. Arch Fam Med 1994; 3: 77479. Ann Rheum Dis 2005; 64: 133742.
11 Smith RC, Korban E, Kanj M, et al. A method for rating charts to 39 Locke GR 3rd, Weaver AL, Melton LJ 3rd, Talley NJ. Psychosocial
identify and classify patients with medically unexplained symptoms. factors are linked to functional gastrointestinal disorders: a
Psychother Psychosom 2004; 73: 3642. population based nested case-control study. Am J Gastroenterol 2004;
12 Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA 99: 35057.
technical review on irritable bowel syndrome. Gastroenterology 2002; 40 Jones TF, Craig AS, Hoy D, et al. Mass psychogenic illness attributed
123: 210831. to toxic exposure at a high school. N Engl J Med 2000; 342: 96100.
13 Sullivan PF, Pedersen NL, Jacks A, Evengard B. Chronic fatigue in a 41 Page LA, Wessely S. Medically unexplained symptoms: exacerbating
population sample: denitions and heterogeneity. Psychol Med 2005; factors in the doctor-patient encounter. J R Soc Med 2003; 96: 22327.
35: 133748. 42 Ring A, Dowrick CF, Humphris GM, Davies J, Salmon P. The
14 Kreutzer R. MCS: the status of population-based research. somatising eect of clinical consultation: what patients and doctors
Int J Hyg Environ Health 2002; 205: 41114. say and do not say when patients present medically unexplained
15 Aaron LA, Buchwald D. A review of the evidence for overlap among physical symptoms. Soc Sci Med 2005; 61: 150515.
unexplained clinical conditions. Ann Intern Med 2001; 134: 86881. 43 Salmon P, Dowrick CF, Ring A, Humphris GM. Voiced but
16 Whitehead WE, Palsson O, Jones KR. Systematic review of the unheard agendas: qualitative analysis of the psychosocial cues that
comorbidity of irritable bowel syndrome with other disorders: what patients with unexplained symptoms present to general
are the causes and implications? Gastroenterol 2002; 122: 114056. practitioners. Br J Gen Pract 2004; 54: 17176.
17 Bungton CA. Comorbidity of interstitial cystitis with other 44 Kirmayer LJ, Groleau D, Looper KJ, Dao MD. Explaining medically
unexplained clinical conditions. J Urol 2004; 2004; 172: 124248. unexplained symptoms. Can J Psychiatry 2004; 49: 66372.
18 Aggarwal VR, McBeth J, Zakrzewska JM, Lunt M, Macfarlane GJ. 45 Raspe H, Matthis C, Croft P, et al. Variation in back pain between
The epidemiology of chronic syndromes that are frequently countries: The example of Britain and Germany. Spine 2004; 29:
unexplained: do they have common associated factors? 101721.
Int J Epidemiol 2006; 35: 46876. 46 Rief W Barsky AJ. Psychobiological perspectives on somatoform
19 Interian A, Gara MA, Diaz-Martinez AM, et al. The value of disorders. Psychoneuroendocrinology 2005; 30: 9961002.
pseudoneurological symptoms for assessing psychopathology in 47 Wood PB. Neuroimaging in functional somatic syndromes.
primary care. Psychosom Med 2004; 66: 14146. Int Rev Neurobiol 2005; 67: 119-63.
48 Cleare AJ. The HPA axis and the genesis of chronic fatigue 72 Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD,
syndrome. Trends Endocrinol Metab 2004; 15: 5559. Ramirez G. Interventions for the treatment and management of
49 Brown RJ. Psychological mechanisms of medically unexplained chronic fatigue syndrome: a systematic review. JAMA 2001;
symptoms: an integrative conceptual model. Psychol Bull 2004; 286: 136068.
130: 793812. 73 Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue
50 Henningsen P. The body in the brain: towards a representational syndrome. Clin Evid 2004; 12: 157893.
neurobiology of somatoform disorders. Acta Neuropsychiatr 2003; 74 Looper KJ, Kirmayer LJ. Behavioral medicine approaches to
15: 15760. somatoform disorders. J Consult Clin Psychol 2002; 70: 81027.
51 Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the 75 Edmonds M, McGuire H, Price J. Exercise therapy for chronic
treatment of irritable bowel syndrome. Cochrane Database Syst Rev fatigue syndrome. Cochrane Database Syst Rev 2004; 3: CD003200.
2004; 1: CD003960. 76 Moayyedi P, Soo S, Deeks J, et al. Pharmacological interventions for
52 Brandt LJ, Bjorkman D, Fennerty B, et al. Systematic review on the non-ulcer dyspepsia. Cochrane Database Syst Rev 2005; 1: CD001960.
management of irritable bowel syndrome in North America. 77 Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for
Am J Gastroenterol 2002; 97: S726. non-ulcer dyspepsia. Cochrane Database Syst Rev 2005; 1: CD002096.
53 Lesbros-Pantoickova D, Michetti P, Fried M, Beglinger C, 78 Laheij RJ, van Rossum, LG, Verbeek AL, Jansen JB. Helicobacter
Blum AL. Meta-analysis: the treatment of irritable bowel syndrome. pylori infection treatment of nonulcer dyspepsia: an analysis of
Aliment Pharmacol Ther 2004; 20: 125369. meta-analyses. J Clin Gastroenterol 2003; 36: 31520.
54 Jones BW, Moore DJ, Robinson SM, Song F. A systematic review of 79 Redstone HA, Barrowman N, Veldhuyzen Van Zanten SJ.
tegaserod for the treatment of irritable bowel syndrome. H2-receptor antagonists in the treatment of functional (nonulcer)
J Clin Pharm Ther 2002; 27: 34352. dyspepsia: a meta-analysis of randomized controlled clinical trials.
55 Kilkens TO, Honig A, Rozendaal N, Van Nieuwenhoven MA, Aliment Pharmacol Ther 2001; 15: 129199.
Brummer RJ. Systematic review: serotonergic modulators in the 80 Allescher HD, Bockenho A, Knapp G, Wienbeck M, Hartung J.
treatment of irritable bowel syndromeinuence on psychiatric Treatment of non-ulcer dyspepsia: a meta-analysis of placebo-
and gastrointestinal symptoms. Aliment Pharmacol Ther 2003; 17: controlled prospective studies. Scand J Gastroenterol 2001; 36: 93441.
4351. 81 Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D.
56 Cremonini F, Delgado-Aros S, Camilleri M. Ecacy of alosetron in Psychological interventions for non-ulcer dyspepsia.
irritable bowel syndrome: a meta-analysis of randomized controlled Cochrane Database Syst Rev 2005; 1: CD002301.
trials. Neurogastroenterol Motil 2003; 15: 7986. 82 Gobel H, Heinze A, Heinze-Kuhn K, Jost WH. Evidence-based
57 Akehurst R, Kaltenthaler E. Treatment of irritable bowel syndrome: medicine: botulinum toxin A in migraine and tension-type
a review of randomised controlled trials. Gut 2001; 48: 27282. headache. J Neurol 2001; 248 (suppl 1): 3438.
58 Poynard T, Regimbeau C, Benhamou Y. Meta-analysis of smooth 83 Prousky J, Seely D. The treatment of migraines and tension-type
muscle relaxants in the treatment of irritable bowel syndrome. headaches with intravenous and oral niacin (nicotinic acid):
Aliment Pharmacol Ther 2001; 15: 35561. systematic review of the literature. Nutr J 2005; 4: 3.
59 Quartero AO, Meineche-Schmidt V, Muris J, Rubin G, de Wit N. 84 Moja P, Cusi C, Sterzi R, Canepari C. Selective serotonin re-uptake
Bulking agents, antispasmodic and antidepressant medication for inhibitors (SSRIs) for preventing migraine and tension-type
the treatment of irritable bowel syndrome. headaches. Cochrane Database Syst Rev 2005; 3: CD002919.
Cochrane Database Syst Rev 2005; 4: CD003460. 85 Tomkins GE, Jackson JL, OMalley PG, Balden E, Santoro JE.
60 Bijkerk CJ, Muris JW, Knottnerus JA, Hoes AW, de Wit NJ. Treatment of chronic headache with antidepressants: a
Systematic review: the role of dierent types of bre in the meta-analysis. Am J Med 2001; 111: 5463.
treatment of irritable bowel syndrome. Aliment Pharmacol Ther 86 Rains JC, Penzien DB, McCrory DC, Gray RN. Behavioral headache
2004; 19: 24551. treatment: history, review of the empirical literature, and
61 Raine R, Haines A, Sensky T, Hutchings A, Larkin K, Black N. methodological critique. Headache 2005; 45 (suppl 2): S92109.
Systematic review of mental health interventions for patients with 87 Bronfort G, Nilsson N, Haas M, et al. Non-invasive physical
common somatic symptoms: can research evidence from treatments for chronic/recurrent headache.
secondary care be extrapolated to primary care? BMJ 2002; 325: Cochrane Database Syst Rev 2004; 3: CD001878.
108292.
88 Bronfort G, Assendelft WJ, Evans R, Haas M, Bouter L. Ecacy of
62 Lackner JM, Mesmer C, Morley S, Dowzer C, Hamilton S. spinal manipulation for chronic headache: a systematic review.
Psychological treatments for irritable bowel syndrome: a systematic J Manipulative Physiol Ther 2001; 24: 45766.
review and meta-analysis. J Consult Clin Psychol 2004; 72: 110013.
89 Astin JA, Ernst E. The eectiveness of spinal manipulation for the
63 Blanchard EB. A critical review of cognitive, behavioral, and treatment of headache disorders: a systematic review of randomized
cognitive-behavioral therapies for irritable bowel syndrome. clinical trials. Cephalalgia 2002; 22: 61723.
J Cogn Psychother 2005; 19: 10123.
90 Lenssinck ML, Damen L, Verhagen AP, Berger MY, Passchier J,
64 Allen LA, Escobar JI, Lehrer PM, Gara MA, Woolfolk RL. Psychosocial Koes BW. The eectiveness of physiotherapy and manipulation in
treatments for multiple unexplained physical symptoms: a review of patients with tension-type headache: a systematic review. Pain 2004;
the literature. Psychosom Med 2002; 64: 93950. 112: 38188.
65 Spanier JA, Howden CW, Jones MP. A systematic review of 91 Melchart D, Linde K, Fischer P, et al. Acupuncture for idiopathic
alternative therapies in the irritable bowel syndrome. headache. Cochrane Database Syst Rev 2001; 1: CD001218.
Arch Intern Med 2003; 163: 26574.
92 Kisely S, Campbell LA, Skerritt P. Psychological interventions for
66 Liu JP, Yang M, Liu YX, Wei ML, Grimsgaard S. Herbal medicines symptomatic management of non-specic chest pain in patients
for treatment of irritable bowel syndrome. with normal coronary anatomy. Cochrane Database Syst Rev 2005;
Cochrane Database Syst Rev 2006; 1: CD004116. 1: CD004101.
67 Goldenberg DL, Burckhardt C, Croord L. Management of 93 Stones W, Cheong YC, Howard FM. Interventions for treating
bromyalgia syndrome. JAMA 2004; 292: 238895. chronic pelvic pain in women. Cochrane Database Syst Rev 2005;
68 Toeri JK, Jackson JL, OMalley PG. Treatment of bromyalgia with 3: CD000387.
cyclobenzaprine: A meta-analysis. Arthritis Rheum 2004; 51: 913. 94 Tu FF, As-Sanie S, Steege JF. Musculoskeletal causes of chronic
69 Sim J, Adams N. Systematic review of randomized controlled trials pelvic pain: a systematic review of existing therapies: part II.
of nonpharmacological interventions for bromyalgia. Clin J Pain Obstet Gynecol Surv 2005; 60: 47483.
2002; 18: 32436. 95 Wyatt K, Dimmock P, Jones P, Obhrai M, OBrien S. Ecacy of
70 Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for progesterone and progestogens in management of premenstrual
treating bromyalgia syndrome. Cochrane Database Syst Rev 2002; 2: syndrome: systematic review. BMJ 2001; 323: 77680.
CD003786. 96 Wyatt KM, Dimmock PW, Ismail KMK, Jones PW, OBrien PMS.
71 Holdcraft LC, Asse N, Buchwald D. Complementary and The eectiveness of GnRHa with and without add-back therapy in
alternative medicine in bromyalgia and related syndromes. treating premenstrual syndrome: a meta analysis. BJOG 2004; 111:
Best Pract Res Clin Rheumatol 2003; 17: 66783. 58593.
97 Wyatt KM, Dimmock PW, OBrien PMS. Selective serotonin 114 Brosseau L, Milne S, Robinson V, et al. Ecacy of the
reuptake inhibitors for premenstrual syndrome. transcutaneous electrical nerve stimulation for the treatment of
Cochrane Database Syst Rev 2002; 3: CD001396. chronic low back pain: a meta-analysis. Spine 2002; 27: 596603.
98 Stevinson C, Ernst E. Complementary/alternative therapies for 115 Khadilkar A, Milne S, Brosseau L, et al. Transcutaneous electrical
premenstrual syndrome: a systematic review of randomized nerve stimulation (TENS) for chronic low-back pain.
controlled trials. Am J Obstet Gynecol 2001; 185: 22735. Cochrane Database Syst Rev 2005; 3: CD003008.
99 List T, Axelsson S, Leijon G. Pharmacologic interventions in the 116 Assendelft WJ, Morton SC, Yu EI, Suttorp MJ, Shekelle PG. Spinal
treatment of temporomandibular disorders, atypical facial pain, and manipulative therapy for low back pain. Cochrane Database Syst Rev
burning mouth syndrome: a qualitative systematic review. 2004; 1: CD000447.
J Orofac Pain 2003; 17: 30110. 117 Manheimer E, White A, Berman B, Forys K, Ernst E. Meta-analysis:
100 Turp JC, Komine F, Hugger A. Ecacy of stabilization splints for acupuncture for low back pain. Ann Intern Med 2005; 142: 65163.
the management of patients with masticatory muscle pain: a 118 Furlan AD, van Tulder MW, Cherkin DC, et al. Acupuncture and
qualitative systematic review. Clin Oral Investig 2004; 8: 17995. dry-needling for low back pain. Cochrane Database Syst Rev 2005;
101 Al-Ani MZ, Davies SJ, Gray RJ, Sloan P, Glenny AM. Stabilisation 1: CD001351.
splint therapy for temporomandibular pain dysfunction syndrome. 119 Ruddy R, House A. Psychosocial interventions for conversion
Cochrane Database Syst Rev 2004; 1: CD002778. disorder. Cochrane Database Syst Rev 2005; 4: CD005331.
102 Rubin GJ, Munshi JD, Wessely S. A systematic review of treatments 120 Chitkara DK, Cremonini F, Talley NJ. Psychotherapy and
for electromagnetic hypersensitivity. Psychother Psychosom 2006; 75: paroxetine: cost eective for severe IBS, or a waste of resources.
1218. Gastroenterology 2003; 125: 155455.
103 Lacour M, Zunder T, Restle A, Schwarzer G. No evidence for an 121 Mease PJ, Clauw DJ, Arnold LM, et al. Omeract 7 Workshop:
impact of selenium supplementation on environment associated bromyalgia syndrome. J Rheumatol 2005; 32: 227077.
health disordersa systematic review. Int J Hyg Environ Health 122 Abraham NS, Moayyedi P, Daniels B, Veldhuyzen Van Zanten SJ.
2004; 207: 113. Systematic review: the methodological quality of trials aects
104 Airaksinen O, Brox JI, Cedraschi C, et al. European guidelines for estimates of treatment ecacy in functional (non-ulcer) dyspepsia.
the management of chronic non-specic low back pain, 2004. www. Aliment Pharmacol Ther 2004; 19: 63141.
backpaineurope.org (accessed April 11, 2006). 123 Rozen D, Sharma J. Treatment of tension-type headache with botox:
105 Staiger TO, Gaster B, Sullivan MD, Deyo RA. Systematic review of a review of the literature. Mt Sinai J Med 2006; 73: 49398.
antidepressants in the treatment of chronic low back pain. Spine 124 Cremonini F, Wise J, Moayyedi P, Talley NJ. Diagnostic and
2003; 28: 254045. therapeutic use of proton pump inhibitors in non-cardiac chest
106 Salerno SM, Browning R, Jackson JL. The eect of antidepressant pain: a metaanalysis. Am J Gastroenterol 2005; 100: 122632.
treatment on chronic back pain: a meta-analysis. Arch Intern Med 125 Fall M, Baranowski AP, Fowler CJ. EAU guidelines on chronic
2002; 162: 1924. pelvic pain. Eur Urol 2004; 46: 68189.
107 Ostelo RWJG, Tulder MW, van Vlaeyen JWS, Linton SJ, Morley SJ, 126 Dickinson WP, Dickinson LM, deGruy FV, Main DS, Candib LM,
Assendelft WJJ. Behavioural treatment for chronic low-back pain. Rost K. A randomized clinical trial of a care recommendation letter
Cochrane Database Syst Rev 2005; 1: CD002014. intervention for somatization in primary care. Ann Fam Med 2003;
108 Guzman J, Esmail R, Karjalainen K, Malmivaara A, Irvin E, 1: 22835
Bombardier C. Multidisciplinary bio-psycho-social rehabilitation for 127 Fink P, Rosendal M, Toft T. Assessment and treatment of functional
chronic low back pain Cochrane Database Syst Rev 2002; 1: disorders in general practice: the extended reattribution and
CD000963. management modelan advanced educational program for
109 Hayden JA, van Tulder MW, Malmivaara A, Koes BW. Exercise nonpsychiatric doctors. Psychosomatics 2002; 43: 93131.
therapy for treatment of non-specic low back pain. 128 Rosendal M, Bro F, Sokolowski I, Fink P, Toft T, Olesen F. A
Cochrane Database Syst Rev 2005; 3: CD000335. randomised controlled trial of brief training in assessment and
110 Heymans MW, van Tulder MW, Esmail R, Bombardier C, Koes BW. treatment of somatisation: eects on GPs attitudes. Fam Pract
Back schools for non-specic low-back pain. 2005; 22: 41927.
Cochrane Database Syst Rev 2004; 4: CD000261. 129 Enck P, Klosterhalfen S. The placebo response in functional bowel
111 Geurts JW, van Wijk RM, Stolker RJ, Groen GJ. Ecacy of disorders: perspectives and putative mechanisms.
radiofrequency procedures for the treatment of spinal pain: a Neurogastroenterol Motil 2005; 17: 32531.
systematic review of randomized clinical trials. Reg Anesth Pain Med 130 Cho HJ, Hotopf M, Wessely S. The placebo response in the
2001; 26: 394400. treatment of chronic fatigue syndrome: a systematic review and
112 Niemisto L, Kalso E, Malmivaara A, Seitsalo S, Hurri H. meta-analysis. Psychosom Med 2005; 67: 30113.
Radiofrequency denervation for neck and back pain: a systematic 131 Rosendal M, Olesen F, Fink P. Management of medically
review of randomized controlled trials. Cochrane Database Syst Rev unexplained symptoms. BMJ 2005; 330: 45.
2003; 1: CD004058.
132 Campbell M, Fitzpatrick R, Haines A, et al. Framework for design
113 Yelland MJ, Mar C, Pirozzo S, Schoene ML, Vercoe P. Prolotherapy and evaluation of complex interventions to improve health. BMJ
injections for chronic low-back pain. Cochrane Database Syst Rev 2000; 321: 69496.
2004; 2: CD004059.