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What is the Evidence for the Efficacy of Treatments for SomatoformDisorders? A Critical Review of Previous Intervention StudiesATHULA SUMATHIPALA, MBBS, DFM, MD, MRCPSYCH, PHD

Objective: To review published literature for the highest level of evidence on the efficacy of treatment for patients with medicallyunexplained symptoms. Methods: A comprehensive literature search was carried out in Cochrane library, Medline (1971–2007),PsychINFO (1974–2006), and EMBASE (1980–2007) to identify pharmacological, nonpharmacological, psychological, and otherinterventions, using the search terms “medically unexplained symptoms,” “somatisation,” “somatization,” “somatoform disorders,”“psychological therapies,” “cognitive behavior therapy,” “pharmacological therapies,” “management,” “therapy,” “drug therapy,”and “anti-depressants” with Boolean operators AND and OR on the entire text. Searches were confined to literature in English.Results: Studies were carried out in primary, secondary, and tertiary care settings. The therapists ranged from medical specialists,psychiatrists, and psychologists to primary care physicians. Three types of interventions (antidepressant medication, cognitivebehavioral therapy (CBT), and other nonspecific interventions) were supported by evidence on the efficacy of treatment for patientswith medically unexplained symptoms. There is more level I evidence for CBT compared with the amount for other approaches.There was only one study reported from the developing world. Conclusions: CBT is efficacious for either symptom syndromes orfor the broader category of medically unexplained symptoms, reducing physical symptoms, psychological distress, and disability.A relatively small number of studies were carried out in primary care, but the trend has been changing over the last decade. Nostudies have compared pharmacological and psychological treatments. Most trials assessed only short-term outcomes. Use ofdivergent selection procedures, interventions, outcome measures, and instruments, and other methodological differences observedin these studies hamper the ability to compare treatment effects across studies. Key words: medically unexplained symptoms,somatization, somatoform disorders, interventions, CBT.

CBT � cognitive behavioral therapy; MUS � medically unex-plained symptoms; RCT � randomized controlled trial; CFS �chronic fatigue syndrome; GP � general practitioner; PPC � psy-chosocial primary care; NCCP � noncardiac chest pain.

INTRODUCTION

A t least one-third of physical symptoms in medical care aremedically unexplained (1). These symptoms are common all

over the world and their health consequences are not a peculiarityto just one culture (2–5). Patients with these symptoms place aheavy burden on the health system because of disproportionateconsumption of health resources (3,4,6,7). Therefore, the need formore research on the best management of medically unexplainedsymptoms (MUS) has been stressed for decades (8,9). The im-portance of developing simple and feasible but effective inter-ventions, and demonstrating their effectiveness when applied inprimary health care by a person without specialized psychiatricskills has also been reiterated (3).

It is therefore important to review from time to time thegaps in the evidence of best management of this challenginggroup of patients. It is also important to review interventionsin primary care and examine the evidence from the developedand developing world, as the available resources may bedifferent in these settings.

The symptoms unexplained by physical diagnosis are aheterogeneous group (2), and occur with depression, anxiety,hypochondriasis, and the other somatoform disorders (2,3,10–

13). But only half of the patients with MUS meet criteria formood and anxiety diagnosis (14,15). Only a minority meetcurrent Diagnostic and Statistical Manual (DSM) criteria forsomatization disorder and less than 30% for somatoform dis-order (15). Many symptom syndromes (approximately 13),such as irritable bowel syndrome and chronic fatigue syn-drome are made up of combinations of MUS that cannot beassumed to be independent of one another. Overlap amongthese conditions is substantial (16–18). There are also patientswith MUS who have neither physical disease nor severemental illness (19).

Lack of clear operational criteria for the entire category ofsomatoform disorders leaves a substantial proportion of pa-tients who present with MUS without a clear indication formedication or psychotherapy (20). But individuals who fallbelow diagnostic criteria can have significant social, emo-tional, and behavioral problems (21) that may respond tointervention. The difficulties in conceptualizing those presen-tations can affect the management of this group of patients.

Hence, the term MUS and patients presenting with MUS,were chosen to include all functional problems rather than thesub-groups who met the operational criteria for somatizationdisorder, conversion disorder, or symptoms syndromes. Informulating the review question and searching for interven-tions, the aim was to look at the issues with the perspective ofpublic health relevance because patients do present withsymptoms rather than with specific diagnostic categories.

Aim

This review attempted to answer the question, what is thehighest level of evidence available for the efficacy of phar-maceutical and nonpharmaceutical interventions for patientswith MUS and where have these studies been carried out?

The strength of evidence of the effectiveness of any inter-vention was assessed from a hierarchy based on study design.Search for evidence was confined to level I (systematic re-

From the Kings College, University of London; the International MentalHealth, Department of Health Service Research, Institute of Psychiatry, UKand the Institute for Research and Development, Colombo, Sri Lanka.

Address correspondence and reprint requests to Dr Athula Sumathipala,Institute of Psychiatry, International Mental Health, Department of HealthServices Research, Kings College, Denmark Hill, London SE5 8AF. E-mail:[email protected]

Received for publication February 7, 2007; revision received August 24, 2007.This article is being co-published by Psychosomatic Medicine and the

American Psychiatric Association.DOI: 10.1097/PSY.0b013e31815b5cf6

889Psychosomatic Medicine 69:889–900 (2007)0033-3174/07/6909-0889Copyright © 2007 by the American Psychosomatic Society and the American Psychiatric Association

view) and level II (randomized controlled trial (RCT)) evi-dence. Adapting a hierarchical approach by examining thehighest level of evidence was the aim. If evidence was presentat level I, the review did not proceed further to obtain level IIevidence. The aim was to identify the gaps and then to reportany recent advances made since the last systematic review.Therefore, level II evidence (individual RCTs, published sincelast available systematic review) were also examined.

METHODSSearch StrategyA comprehensive literature search was carried out using electronic data-

bases: Cochrane library databases (up to 2007), Medline (1966–2007),PsychINFO (1974–2006), and EMBASE (1980–2007). Searches were con-fined to literature in English. In Cochrane library databases (1971–2007), thesearch terms “medically unexplained symptoms,” “somatisation,” “somatiza-tion,” and “somatoform disorders” were used first for a simple search, foreach search term separately, followed by an advanced search combining allsearch fields with the Boolean operator OR in abstract, key words, or title.These search terms were then used again with the Boolean operator AND withthe search fields individually and in combinations; psychological therapies,cognitive behavior therapy, pharmacological therapies, management, therapy,drug therapy, and antidepressants.

Results for Cochrane systematic reviews, other systematic reviews, andRCTs were scrutinized for suitable papers for this review (Table 1). Searcheswere repeated for Medline (1966–2007) and PsychINFO (1974–2006), aswell as EMBASE (1980–2007, week 26), using the OVID database. How-ever, the search terms were modified to suit the search strategies for thesedatabases. To ensure a comprehensive review, search for literature wassupplemented by examining the reference lists of the papers generated fromthe original searches.

Selection of StudiesThe author with another colleague jointly scanned the abstracts identified

by the electronic searches to select the potentially suitable papers. Abstractseligible for inclusion were systematic reviews or randomized trials of apsychological (Table 2), pharmacological, or any other type of interventioninvolving an adult, with patients defined as medically unexplained symptoms,unexplained symptoms, somatoform disorders, somatisation, somatization,functional somatic symptoms, and the abstract was written in the Englishlanguage.

Data ExtractionInitially, all abstracts that appeared relevant were selected as potentially

suitable. The same two assessors then scrutinized them more carefully fordefinitive inclusion. All abstracts selected were checked for duplications,which, if found were excluded. Systematic reviews or RCTs exclusively onsymptom syndromes, such as irritable bowel syndrome, chronic fatigue syn-drome (CFS), and fibromyalgia, were excluded. Systematic reviews of MUSincorporating symptom syndromes, however, were included. Papers focusingon children and adolescents were also excluded.

RESULTSCochrane searches aggregated to 13 abstracts on systematic

reviews and 421 RCTs during simple search. The combinedsearch of all search words yielded 13 abstracts of systematicreviews and 355 of RCTs. The cases were performed inprimary, secondary, or tertiary care. The therapists rangedfrom medical specialists, psychiatrists, and psychologists toprimary care physicians. Search results from Medline,PsychINFO, and EMBASE did not yield any suitable system-atic reviews. However, there were RCTs; 12, 6, and 8 fromthese respective databases.

Full-text papers of six potentially relevant systematic re-views were studied in detail. One paper on antidepressants andtwo on psychological interventions were excluded as theywere not strictly systematic reviews even though they wereotherwise valuable reviews. One systematic review from athesis (26) and two other systematic reviews (27,28) wereknown to the author through previous work. Six systematicreviews were finally included in the review. The last system-atic review was published in 2002 and reviewed studies up to2000.

Two assessors identified 108 abstracts of RCTs that wereretrieved for further scrutiny. Seventeen duplicate publicationswere identified and excluded. Fourteen trials published since2000 were selected for this review.

TABLE 1. Search Results From Cochrane Library

Search field(s) Cochrane Reviews Other Reviews RCT

Medically unexplainedsymptom/s

One relevant protocol onconsultation letter (22)

One on CBT for MUS (23) 20 total but 12 were potentiallysuitable

Somatization One review on psychosocialintervention by GP not relevant

Nil 20 total but 3 were potentiallysuitable

Somatization Nil One—CBT for somatization andsymptom syndromes (24)

188 total but 29 were potentiallysuitable

Somatoform disorder/s Two—one on psychodynamicpsychotherapies for CMD, oneon psychosocial intervention byGP. Both not relevant

10 in total but only 3 wererelevant: CBT for MUS (23),CBT for somatization andsymptom syndromes, CBT forsomatization and symptomsyndromes (24), andpsychosocial interventions forMUS (25)

193 total but 78 were potentiallysuitable

Combination of MUS,somatisation, somatization,somatoform disorders,

3 identified but only 1 relevantprotocol on consultation lettersfor MUS (22)

10 identified, only 3 suitable(23–25)

355 but 311 potentially suitable

A. SUMATHIPALA

890 Psychosomatic Medicine 69:889–900 (2007)

Level I Evidence (Systematic Reviews)Pharmacological Therapy

Only one systematic review on antidepressant medicationincluding a meta-analysis qualified.

Antidepressant Medication

O’Malley et al. (27) identified papers by searching Medline(1966–1998), PsychLIT (1974–1998), EMBASE/ExcerptaMedica (1974–1998), the Cochrane Library, the Federal Re-search in Progress database, and bibliographies of relevantarticles. The emphasis was on adults with MUS but mainlythose with at least one of six symptom syndromes: headache,fibromyalgia, functional gastrointestinal syndromes, idio-pathic pain, tinnitus, and chronic fatigue. Ninety-four RCTscompared antidepressant medications; tricyclic antidepres-sants, selective serotonin reuptake inhibitors (SSRI) with pla-cebo, and nonantidepressant medications. The majority ofparticipants were women. Sixty-four (69%) studies demon-strated improvement of one or more of the following out-comes: global assessment (patient or physician), summarysymptom index score, or pain severity score.

A meta-analysis showed benefits from antidepressant med-ication; the standard mean difference was 0.87 (95% confi-dence interval (CI) 0.59–1.14), or dichotomized outcomes ofimprovements, odds ratio of 3.4 (95% CI 2.6–4.5). The ab-solute percentage difference in improvement was 32% and thenumber needed to treat for the benefit of one additional patientwas four.

O’Malley et al. (27) concluded that antidepressant medica-tion could be effective in improving outcome, including symp-toms and disability. However, high withdrawal rates were

seen in 63% of the studies. Side effects were reported only in37% of the studies.

Psychological therapy

Cognitive Behavioral Therapy

Five systematic reviews have shed light on the use ofCBT showing varying success in the management of pa-tients with MUS. Kroenke and Swindle (24) searched forstudies published between 1966 and 1999. The studies wereeither RCTs or nonrandomized trials of CBT or cognitivetherapy (CT) for somatization, somatoform disorders, orpersistent symptoms or symptom syndromes. All these tri-als (randomized or not) included a control group not re-ceiving CBT or CT interventions.

Of 31 trials reviewed, 29 were randomized. Eleven wereperformed in the United States, seven in the United Kingdom,five in Netherlands, four in Australia, three in Sweden, andone in Germany. Twenty-five studies targeted specific symp-tom syndromes; irritable bowel, back pain, chronic fatiguesyndrome, chest pain, tinnitus, or fibromyalgia. Only six fo-cused on general somatization, three of those were on patientswith MUS and three on those with hypochodriasis. Moststudies (n � 29) included patients referred to secondary ortertiary care. Only two trials were carried out in primary care:those reported by Speckens et al. (29) and Van Dulmen et al.(30).

Of 1689 patients, the majority were women and 803 re-ceived CBT. Primary outcomes were physical symptoms, psy-chological distress studies, or functional status but some hadmore than one primary outcome. Physical symptoms appeared

TABLE 2. Summary of the Findings of Systematic Reviews on Psychological Interventions

Review Author(s) Patient Group Intervention Conclusions by Authors

O’Malley MUS including symptomssyndromes

Antidepressants Effective in improving outcome, includingsymptoms and disability

Kroenke and Swindle (24) Somatization, somatoformdisorders, or persistentsymptoms

Individual or group CBT CBT effective for patients with somatization orsymptom syndromes; reduction of physicalcomplaints could occur whether or notpsychological distress

Blankenstein (26) Somatisation Individual of group CBT CBT effective for somatization and symptomsyndromes but the evidence for theeffectiveness of CBT for somatization waslimited

Nezu et al. (23) MUS, somatization, somatoformdisorders, or symptomsyndromes

Individual or group CBT CBT effective for all 4 categories of patients;improvement on physical symptoms andassociated mood disturbances, and overallphysical and social functioning for patientswith MUS and CFS

Allen (25) Somatization, somatoform,psychogenic, functionalsomatic syndrome

Psychosocial interventions Effect sizes are modest at best. Althoughbeneficial, have not shown a lastinginfluence on the physical complaints ofpolysymptomatic somatizers

Looper and Kirmayer (28) Different diagnostic categoriesor symptom syndromes

CBT Most studies used multiple treatmentstrategies but studies support the efficacy ofindividual CBT for symptom syndromes andMUS

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REVIEW OF INTERVENTION STUDIES

891Psychosomatic Medicine 69:889–900 (2007)

to be the most responsive. CBT patients improved more thancontrol subjects did in 71% of the studies. Group therapy, asbrief as five sessions, was reported to be efficacious and itsbenefits were sustained for up to 12 months.

Kroenke and Swindle (24) concluded that CBT, bothindividual and group therapy, could be an effective treat-ment for patients with somatization or symptom syndromes.Benefits in reduction of physical complaints could occur whetheror not psychological distress was ameliorated.

Kroenke and Swindle (24) recommended further evaluationson optimal sequencing of CBT in treating primary care patentsand identification of those most likely to accept and respond totherapy. Other issues identified were the need for flexible inter-ventions having varying degrees of emphasis on cognitive andbehavioral components, different numbers of session provided,therapists in most studies were mental health professionals, andmostly short-term follow-up on referred populations.

Blankenstein (26) carried out a systematic review of allrandomized trials of treatment for somatization, which wereeither performed in or applicable to general practice. Only 10trials were identified as appropriate for the review. Threestudies reported using CBT, one of which was group CBT; allwere identified as carried out in primary care (29,31,32).

Blankenstein (26) concluded that CBT could be an effec-tive treatment for somatization and symptom syndromes.However, he also noted that the number of trials was small andmethodological quality was mediocre; thus, the evidence forthe effectiveness of CBT for somatization was limited.

Looper and Kirmayer (28) reviewed studies from 1970 toFebruary 2001 having possible overlap with Kroenke andSwindle (24). The difference of this review is that the analysiswas carried out separately for the different diagnostic catego-ries and symptom syndromes. Evidence for the effectivenesswas found by the following:

1. Four RCTs using relatively brief individual CBT wereeffective for hypochondriasis (33–36);

2. Four RCTs for body dysmorphic disorders (37–40);3. Four RCTs on “undifferentiated somatoform disorder”:

chronic fatigue syndrome (41–44);4. Four RCTs on “undifferentiated somatoform disorder”;

noncardiac chest pain (45–48);5. Four RCTs on “undifferentiated somatoform disorders”;

MUS. All four studies were categorized as primary carebased (29,49,31,32).

Looper and Kirmayer (28) concluded that there has beenconsiderable progress in establishing the efficacy of CBT forthe treatment of somatoform disorders and that the evidencesupports the efficacy of individual CBT for the treatment ofhypochondriasis, body dysmorphic syndrome (BDD), chronicfatigue, noncardiac chest pain, and MUS. The efficacy ofgroup therapy was also demonstrated in BDD and somatiza-tion disorder. Effects were of moderate to large magnitude andthe authors recommend CBT as the first line of treatment.

However, they noted that the optimal and minimum dura-tion of treatment and value of maintenance therapy need to be

established. They identified many important methodologicalconsiderations. Nonavailability of standardized treatmentmanuals, not making a blind-rating outcome, and use of in-tention to treat analysis were the other issues highlighted.

Nezu et al. (23) reviewed 37 studies but only 19 wererandomized trials. Nine had targeted MUS, 7 on chronicfatigue syndrome, 16 on fibromyalgia, and 5 on noncardiacchest pain. Significantly, a larger number of studies usedgroup therapy. Five of the nine studies on MUS were per-formed in the United Kingdom and Sweden.

Nezu et al. (23) also analyzed studies separately for thedifferent diagnostic categories and symptom syndromes. Ofnine studies on MUS, only six were RCTs (29,49,31,50–52).The authors concluded that CBT seems effective for reductionof a wide range of physical symptoms, and physical and socialfunctioning. Of seven studies on chronic fatigue syndrome,five were RCTs (41,42,44,53,54). CBT improved CFS symp-toms, activity, function, and distress. Of the above highlymixed group of 16 studies, 3 were group interventions, 4 wereindividual RCTs, and 1 was inpatient care; even the treatmentmethods were highly variable. Nonetheless, the authors con-cluded that CBT was beneficial in decreasing psychologicaland physical symptoms distress and increase quality of life.Five studies were identified on undifferentiated somatoformdisorder: noncardiac chest pain (45,47,48,55,56); one includedgroup therapy. CBT was beneficial in reducing chest pain anddistress.

The overall duration of sessions ranged from six 40-minutesessions to eight 3-hour group sessions for MUS; 30- to60-minute outpatient interventions to 10 weeks of inpatienttreatment for CFS; nine sessions over 3 weeks to 14 weeks oftriweekly intervention for studies of FMS; and 4 to 12 weeksfor studies of noncardiac chest pain (NCCP).

The review concluded that, overall, CBT appeared to beeffective for all four categories of patients with improvementon a wide range of physical symptoms and associated mooddisturbances, and overall physical and social functioning forpatients with MUS and CFS. There was a significant decreasein certain psychological and physical symptoms, includingimproved quality of life, pain, tender points, physical condi-tion, emotional distress, and self-efficacy beliefs in patientswith fibromyalgia, and decreased chest pain, activity limita-tion, and emotional distress in patients with noncardiac chestpain.

Allen et al. (25) searched the literature from 1966 throughJanuary 2001. Studies were selected if they compared any psy-chosocial intervention with a control intervention in the treatmentof multiple unexplained physical symptoms. Interestingly, theauthors used the term “polysymptomatic somatizers” and in-cluded only multiple medically unexplained symptoms, an ex-treme group, and selected 34 RCTs for their review. Thesestudies included 2 on somatization disorder, 15 on irritablebowel, 5 on CFS, and 12 on FMS. Allen et al. used the term“psychosocial interventions” instead of psychological.

Outcome measures were intensity and frequency of phys-ical symptoms, physical distress, psychological distress, and

A. SUMATHIPALA


functional impairment. They observed methodological short-comings and lack of evidence on long-term outcome in over75% of studies. Their conclusion was that “although seem-ingly beneficial, psychosocial treatments have not yet beenshown to have a lasting and clinically meaningful influence onthe physical complaints of polysymptomatic somatizers” (25).

Psychodynamic Psychotherapy

There were no systematic reviews on psychodynamicpsychotherapy.

Family Therapy

There were no systematic reviews on family therapy.

Other Interventions

Consultation Letter

There was no systematic review on consultation letters buta Cochrane protocol was available proposing to assess theeffectiveness of consultation letters to assist general practitio-ners or occupational health physicians in the treatment ofpatients with multiple MUS in primary care. There were noother systematic reviews.

Level II Evidence: Individual RCTPsychodynamic Psychotherapy

Guthrie (57) identified three studies using psychodynamicpsychotherapy for patients with “somatisation disorders” (58–60) and concluded that the small number of studies makes itdifficult to generalize the results to other somatic conditions.

Bassett and Pilowsky (58) reported an RCT that compared12 sessions of psychodynamic psychotherapy with six ses-sions of supportive therapy for patients in a pain clinic. Asmall difference in pain reduction was shown between the treat-ment and control groups. Svedlund (59) compared the effective-ness of routine medical treatment with dynamic therapy forpatients with irritable bowel syndrome from an outpatientclinic. Patients who received 12 sessions of psychotherapyshowed a significantly greater reduction in gastrointestinalsymptoms. Guthrie et al. (60) reported a placebo-controlledtrial involving 100 patients with chronic unresponsive symp-toms of irritable bowel syndrome. The treatment of sevensessions of exploratory psychotherapy was compared to thecontrol of seven sessions of supportive listening. They re-ported significantly greater improvement in the treatmentgroup in reduction of symptoms.

Family Therapy

Empirical studies using family therapy for MUS or symp-tom syndromes are almost nonexistent. Real et al. (61) re-ported a study that used brief family therapy for 18 patientswho suffered from somatoform disorder for at least 1 year. Ageneral practitioner trained in short family therapy, appliedtherapy under the supervision of a trained psychologist. Onlythe abstract is available and it reports 61.1% “therapeuticsuccess” (61).

Reattribution

The reattribution model consists of an interview with anassessment and a management part. There are three phases inthe session with the patient a) feeling understood, b) changingthe agenda, and c) making the link (62). Evaluation of theteaching package on the reattribution model revealed that theskills can be effectively learned (63). Training family practi-tioners in reattribution to manage patients with MUS is fea-sible and acceptable, and its effectiveness is measurable inroutine primary care (64).

Larisch et al. (65) in a two-level cluster randomized trialcompared psychosocial interventions based on the modifiedreattribution model for somatizing patients in general practice(GP) with those of nonspecific psychosocial primary carealone. Forty-two GPs were randomized; 23 to intervention and19 to the control arm. In total, 127 patients were included.Primary outcome measures were somatoform symptoms andquality of life. These revealed a reduction of physical symp-toms (p � .007), an improvement in physical functioning (p �.0172), and a reduction of depression (p � .0211) and anxiety(p � .0388) in the intervention group compared with in thecontrol group at the 3-month follow-up. Results no longerremained significant after controlling for baseline and covari-ate variables for most of these variables, although physicalsymptoms were still reduced at 6-month follow-up (p � .029).Compared with nonspecific psychosocial primary care, theeffects of reattribution techniques were small and limited tophysical symptoms.

Problem-Solving Approach

Wilkinson and Mynors-Wallis (66) reported a pilot study ofproblem-solving therapy for the treatment of MUS in 11primary care patients. Ten of the 11 patients completed be-tween 7 and 10 treatment sessions. The mean SymptomChecklist (SCL)-90 score was 90 before the treatment and fellto 50 after the treatment (t � 5.4, p � .001); the mean WhitleyIndex score was 8.9 before treatment and dropped to 5.1 (t �3.1, p � .005), and the mean number of visits to generalpractitioner reduced from 4.9 to 2.1.

Therapeutic Benefits Arising From anAssessment/Consultation

Patients with MUS who were randomized to receive “pos-itive” suggestion (told that they had a definite diagnosis andthey would be better soon) compared with “negative” sugges-tion (that their diagnosis and outcome were uncertain), didsignificantly better in terms of both satisfaction and subjectiveimprovement (64% versus 39%; p � .001) than the negativegroup did (67).

Smith et al. (8) in a crossover RCT tested the efficacy of apsychiatric consultation in reducing the medical costs of pa-tients with somatization. Thirty-eight patients in interventionor control arms were followed up for 18 months. The inter-vention consisted of a psychiatric consultation leading tosuggestions on the management for the primary care physi-cians. After the psychiatric consultation, the quarterly health care

TREATMENT



charges for the first treatment group declined by 53% (p � .05).The quarterly charges in the control group were significantlyhigher than those in the treatment group (p � .05). After thecontrol group crossed over, their quarterly charges declined by49% (p � .05). The reductions in expenditures in both groupswere due largely to decreases in hospitalization. They concludethat psychiatric consultation reduced subsequent health care ex-penditures of patients with somatization disorder without affect-ing changes in health status or the patients’ satisfaction with theirhealth care.

Consultation Letter

Smith et al. (68) conducted another RCT with 51 physi-cians treating 56 somatizing patients who had a history ofseeking help for 6 to 12 unexplained physical symptoms. Atthe start of the experiment, physicians randomized to thetreatment condition received a psychiatrist’s consultation let-ter recommending a specific management approach. Physi-cians randomized to the control then crossed over to receivethis letter after 12 months. Data on health outcomes andcharges were collected every 4 months for up to 2 years.Patients in the intervention arm reported significantly in-creased physical functioning and remained stable during theyear after the intervention. The intervention reduced annualmedical care charges by $289 (95% CI $40–$464) in 1990,which equates to a 32.9% reduction in the annual median costof their medical care. Somatizing patients with a lifetimehistory of 6 to 12 medically unexplained symptoms benefitedby the treatment based on the recommendations after a psy-chiatric consultation. The consultation is cost-effective andreduces subsequent charges for medical care, and improveshealth outcomes in a chronically impaired population.

Rost et al. (69) performed an RCT in which 59 primarycare physicians received a psychiatric consultation letter pro-viding treatment recommendations for 73 patients either atbaseline or at the end of the year-long study. Patients ofdoctors receiving the consultation letter reported greater phys-ical capacity than did patients of control physicians (meandifference � 17.9, 95% CI 1.0–34.9) with a $466 reduction(95% CI $132–$699) in health care charges. In addition to anet 21% reduction in health care charges for the typicalsomatization disorder patient, the consultation letter improvedphysical functioning in a group of highly impaired subjects.Psychiatric consultation letters are also associated with reduc-tion of health costs either as part of individual care (70) orwith additional group therapy (52).

Progress Made Over the Last Decade

RCTs carried out since the last systematic review in 2002(RCTs up to 2001) are presented in Table 3. Overall, therewere 14 RCTs that qualified for the review; 7 from primarycare, 5 from secondary care, and 3 from tertiary care. All werefrom the developed world and were selected samples of de-fined study populations introducing some selection bias. Threedrug trials were double blind (72,74,79). Understandably,none of the psychotherapy trials could be double blinded, but

the efforts to mask the assessors were described in six trials(65,71,76,77,80,81). Prior power calculations were reported infive studies, (73,74,76,80,83), effect sizes of treatment differ-ence were reported in seven (73,74,76,78,80,82,83), and long-term outcome in three studies (73,82,83).

DISCUSSIONThe review reveals that two types of interventions, antide-

pressant medication and CBT, are supported by level I evi-dence as benefiting patients with MUS. In addition, there islimited level II evidence for other pharmacological and psy-chological interventions: assessment or consultation includingcollaborative care model, consultation letter, reattribution,bioenergetics exercise, St John’s wort extract (LI 160), andlevosulpiride. However, there were no studies comparing theefficacy between pharmacological and psychological treat-ments for MUS.

All six systematic reviews reached similar conclusions, thatCBT may be efficacious for these disorders whether definedas symptom syndromes or grouped under the broader headingof MUS. The impact of CBT has been shown to range fromreduction of physical symptoms to psychological distress anddisability. However, all reviews recommended further high-quality studies and noted the low number of studies in primarycare.

There has been a positive trend over the last decade towardmore studies being performed in primary care but, still, thereis a crucial and significant deficit of intervention research forMUS in the developing world. Only one study has beenreported to date (32). It could be because of the publicationdivide (84) or simply a result of limited research capacity inthe developing world (85).

Antidepressant Medication

Evidence for the effectiveness of antidepressants is avail-able for different subgroups of somatoform disorders. Thereisn’t much new evidence on other medication.

The O’Malley et al. (27) review did not comprehensivelyaddress the issue of side effects. Only 37% of the studies coveredhad examined the issue of side effects and the high withdrawalrates of 63% in such studies may be an indicator of this problem.The potential for side effects is a serious consideration whenusing antidepressants, particularly tricyclics, for patients withMUS because the side effects in response to medication may bemisinterpreted as worsening of symptoms.

In a commentary on the work of O’Malley et al. (27), Price(86) concluded that for MUS or symptoms syndromes, anti-depressant medication could be effective in improving out-come, including symptoms and disability. However, Pricenoted that for antidepressants there was as yet no informationon the optimum dose, duration of treatment, or long-termoutcome and there was no firm evidence that antidepressantsor any other pharmaceutical agent can be regarded as the bestapproach for treating MUS.

There were two recent trials on St John’s Wort (72,74)reporting efficacy for MUS independent of depressive mood.

A. SUMATHIPALA


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A. SUMATHIPALA


Werneke (87) discussed some methodological issues of theMuller study (74); exclusion of placebo responders after theplacebo run-in phase, leading to a bias in favor of St John’sWort, and that the trial was conducted over a shorter period of6 weeks. Therefore, more replication studies were recom-mended.

Cognitive Behavioral Therapy

There is more level I evidence for CBT compared with forother approaches and the evidence is increasing. CBT seemsto be effective in the reduction of a wide range of physicalsymptoms and associated mood disturbance, as well as inproducing improvements in overall physical and social func-tioning.

Antidepressants are moderately effective for MUS andeffect sizes are homogenous across functional syndromes butno trials have compared antidepressants with CBT. However,there are other reasons, beyond efficacy and empirical evi-dence, for the choice of CBT over antidepressants. Fewer than50% of patients with chronic diseases maintain compliance inthe longer term (88,89). Compliance by patients with MUSwill be a particular problem as they seek treatment from manydifferent categories of therapists. The cognitive behavioralmodel accommodates each factor that contributes to the pa-tient’s distressed state. Working with this model, the therapistis able to go beyond the medical model that searches for aphysical cause and treatment by prescription of medication,which has so far failed to help the patient. Another possibleadvantage is, in contrast to antidepressant medication, patientsdo not experience unwanted side effects from CBT.

Lack of clarity on what interventions qualify to be defined asCBT remains a problem. Although Nezu et al.’s (23) reviewclaimed to be on CBT, the interventions reported were diverseand may not strictly fall under the category of CBT. Relaxationtraining, problem-solving training, assertiveness training, visual-ization, use of behavioral experiments, graded increases in activ-ity level, coping-skills training, education, biofeedback, exercise,and breathing training were included as variants of CBT. Ismailet al. (90) categorized psychological therapies into four groups:supportive or counseling therapy, CBT, psychoanalytically in-formed therapies, and family systems therapy, and some of theabove techniques were classified as counseling.

On the contrary, Allen et al. (25) used the definition “psy-chosocial interventions” instead of psychological. However,from the results it seems they have included trials usingshort-term dynamic psychotherapy, relaxation, cognitive ther-apy, behavioral therapy, and individual and group CBT.Hence, it may be misleading to categorize them together aspsychosocial interventions.

Existing evidence on brief dynamic psychotherapies is verylimited for MUS. Dynamic psychotherapy has still not shownconvincingly better results than placebo or good clinical caredo but harm may also occur from dynamic intervention (91).Although there are elements common to both these therapies,there are differences too. CBT focuses more on practicalmethods of managing current symptoms whereas dynamic

psychotherapy concentrates on the historical origin of symp-toms and on relationships including that of the patient with thetherapist.

Other InterventionsAssessment as an Intervention

An assessment itself without formal psychotherapy hastherapeutic effects (86). A rounded clinical assessment mightmodify such cognitive factors as symptom attribution andimprove outcome (92).

The trials that include a comprehensive assessment, thus,seem to have a positive impact on the outcome of patients withphysical symptoms whether they are medically explained orunexplained. The factor influencing the outcome may be aresult of change in cognition.

Limitations of the Intervention Studies Carried Outto Date

Most of the studies have adopted divergent selection pro-cedures, interventions, outcome measures, and instrumentsand these clinical and methodological differences hampercomparison of treatment effects. Many issues remain unan-swered and most trials have assessed short-term outcomesonly. Although MUS are common in primary care, moststudies up to 2000 were not carried out in primary care.However, it is encouraging to see that over the last few yearsmore studies have been conducted in primary care; but it isstriking that evidence from the developing world is verylimited.

Many studies have not provided equal time for the controlsand for the intervention group. Finally, another limitation ofthis review is that it is confined to literature in English.

Implications for Classification

The challenges posed by the existing systems on classify-ing MUS pose similar challenges and limitations in reviewingintervention studies on MUS as well. The variation of thenumbers of reviews and RCTs retrieved by using differentsearch words for the same problem is a good example. Thelimitations imposed by these divergent criteria seriously ham-per a comparison of the reported work. Maybe the terms“thick folder patients,” “crocks,” “hysterics”, “the terror of thedoctor,” “problem patients,” “painful woman,” “hypochon-driac,” and “amplifiers” (93) are replaced with the moresophisticated MUS, somatization, somatoform disorders, func-tional syndromes but the alternatives are still diverse.

Directions for Future Research

Treatment of patients with MUS involves a complexintervention, consisting of different components, whichmay act both independently and interdependently (94) butthe active component may not be easily defined. Thera-pists’ and patients’ characteristics, delivery, frequency,timing of trial procedures, recruitment into a trial per se,availability of information leaflets, the consent process,nonspecific effects of structured appointments, and the

TREATMENT



regular structured follow-up assessment, all may be part ofactive components.

Hence, future research should consider using factorial de-signs; compare the efficacy of CBT with other alternativetreatment, antidepressants in particular and combinations (78);group and individual CBT therapy (28); other combined re-gimes (81); or stepped care (95). Optimum treatment intensityor duration (i.e., dose) and place of booster sessions (28)should be considered. Qualitative work to identify strategiccomponents to develop a culturally sensitive and patientfriendly intervention should also be embedded with RCTs(94). As most studies used short-term benefits, it is crucial tomonitor longer-term benefits (80).

Even if evidence exists for efficacy, we need more prag-matic controlled trials to have a chance of implementing thesetherapies in more realistic clinical settings (23,16) and that canbe carried out with relevance to accessibility (96).

More studies are warranted in the developing world withmore locally sensitive and culturally appropriate interventions.Evidence-based guidelines on treatment will be useful only ifthe subjective elements of patients’ preferences and values areacknowledged and explored (89).

I thank Kethakie Sumathipala and Sudath Samereweera for theirinvaluable assistance in the literature search and help with themanuscript.

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