Medically unexplained physical symptoms (MUPS) is a label used to describe physical symptoms for which adequate evidence regarding the presence of an underlying pathophysiological process is absent following appropriate examination and investigation.

MUPS are very common in healthcare settings, and in fact almost one third of all people presenting with physical symptoms have MUPS (Kirmayer et al., 2004). Also, the presence of MUPS is a key feature of conditions included in the diagnostic category of “somatoform disorders”.

In a recent Cochrane Systematic Review, van Dessel and colleagues give an overview of the evidence for non-pharmacological interventions for MUPS and somatoform disorders.

Methods

The authors included randomized clinical trials (RCTs) and cluster RCTs involving adults who were primarily diagnosed with a somatoform disorder, or who were characterized with MUPS (assessed with a validated scale), as their primary problem. Studies in which participants were diagnosed with one specific functional syndrome or symptom (e.g., fibromyalgia) were excluded.

Patients had to be assigned to a non-pharmacological intervention (psychological or physical therapies), which had to be compared with usual care, waitlist control, attention or psychological placebo, enhanced or structured care, or another psychological or physical therapy intervention, alone or in combination.

Primary outcome measures were

• Severity/intensity of somatic symptoms (assessed primarily with validated scales and, in the case none was available, with multiple visual analogue or non-validated scales)
• Acceptability of treatment (assessed as the complement of the proportion of trial participants who dropped out from either the experimental or the comparator group)

Secondary outcomes included: depression and anxiety; dysfunctional cognitions, emotions or behaviors (participant rated); adverse events; treatment response (responder versus non-responder); functional disability and quality of life; healthcare use.

Outcomes were analysed at the following time points (when available):

1. Post-treatment
2. Within 12 months after the end of treatment
3. More than 12 months after the end of treatment

Included studies were assessed for methodological quality, using the following criteria from the Risk of Bias Assessment tool developed by Cochrane Collaboration: random sequence generation, allocation concealment, blinding of participants and study personnel, blinding of outcome assessors, incomplete outcome data, selective outcome reporting, other sources of bias. Moreover, the authors also evaluated treatment fidelity, researcher allegiance and therapist qualifications.

Effect sizes (ES) were calculated as standardized mean differences for continuous data or by risk ratios for dichotomous data.

Results

21 studies met the inclusion criteria and were included in the meta-analysis. Only one of these was a cluster RCT. All studies investigated the efficiency of some form of psychotherapy. Out of these, two thirds (14 studies) investigated forms of cognitive behavioral therapy (CBT). No study examined physical therapy.

• Risk of bias was high for most studies for the criteria regarding blinding (participants, therapists, outcome assessors), but this was also due to the nature of the interventions. With most psychological interventions, it is impossible to ensure blinding of participants and therapists. For the other criteria considered, risk of bias was low.
• Adverse events were rarely reported.
• Psychological therapy resulted in less severe symptoms at the end of treatment (SMD= -0.34, 95% CI -0.53 to -0.16) compared to usual care or a waitlist. However, the overall quality of evidence for this comparison was low
• Psychological therapies resulted in a 7% higher proportion of drop-outs during treatment than usual care.
• When the analysis was restricted to CBT, results were similar, both for symptom severity, as well as for drop-out.
• Psychological therapy was not different from enhanced care for symptom severity assessed at the end of treatment, but this comparison was based on only five studies and their overall quality was low. However, psychological therapies were less acceptable than enhanced care in term of drop-outs.
• Psychological therapies were more efficient for symptoms of anxiety and depression than usual care and waitlist at the end of treatment, but only when symptoms were assessed on clinician-based and not self-report measures. These results were based on a small number of studies, only 3 for anxiety, and 6 for depression.

Conclusions  

The authors concluded that:

All psychological therapies combined were superior to usual care or waiting list condition for symptom severity, our first primary outcome, but effect sizes were small. As a single treatment, only cognitive behavioural therapy (CBT) was adequately studied to allow conclusions for practice.

However, they also emphasized that:

In daily practice, a substantial percentage of people with medically unexplained physical symptoms (MUPS) may not be willing to accept psychologically oriented treatments. Whether such acceptance is associated with the effect of psychological treatments for the total MUPS population was not clear.

The authors underscored that the quality of the evidence on which the review was based was low to moderate. They also drew attention to the fact that the reduced number of studies included in the review prevented them from analyzing and drawing conclusions about the impact of characteristics such as the therapist’s profession and experience, treatment intensity or location, on the efficacy of the interventions.

Limitations

• The number of included studies was small, and consequently many comparisons were based on a very small number of effect sizes, making results extremely volatile and precluding the authors from drawing firm conclusions or implications for practice.
• The reduced number of studies effectively prevented the analysis of publication bias for most comparisons, since funnel plots could not be constructed with so few points.
• Heterogeneity was a problem for most comparisons, again making results unstable and difficult to interpret.
• The overall quality of the studies included in the review was low.

Links

Van Dessel, N., den Boeft, M., van der Wouden, J.C., Kleinstäuber, M., Leone, S.S., Terluin, B., Numans, M.E., van der Horst, H.E., van Marwijk, H., 2014. Non-pharmacological interventions for somatoform disorders and medically unexplained physical symptoms (MUPS) in adults. Cochrane Database Syst Rev 11, CD011142. doi:10.1002/14651858.CD011142.pub2

Kirmayer, L.J., Groleau, D., Looper, K.J., Dao, M.D., 2004. Explaining medically unexplained symptoms (PDF). Can J Psychiatry 49, 663–672.