Abstract: We included 21 studies with 2658 randomised participants. All studies assessed the effectiveness of some form of psychological therapy. We found no studies that included physical therapy. Fourteen studies evaluated forms of cognitive behavioural therapy (CBT); the remainder evaluated behaviour therapies, third-wave CBT (mindfulness), psychodynamic therapies, and integrative therapy. Fifteen included studies compared the studied psychological therapy with usual care or a waiting list. Five studies compared the intervention to enhanced or structured care. Only one study compared cognitive behavioural therapy with behaviour therapy. Across the 21 studies, the mean number of sessions ranged from one to 13, over a period of one day to nine months. Duration of follow-up varied between two weeks and 24 months. Participants were recruited from various healthcare settings and the open population. Duration of symptoms, reported by nine studies, was at least several years, suggesting most participants had chronic symptoms at baseline. Due to the nature of the intervention, lack of blinding of participants, therapists, and outcome assessors resulted in a high risk of bias on these items for most studies. Eleven studies (52% of studies) reported a loss to follow-up of more than 20%. For other items, most studies were at low risk of bias. Adverse events were seldom reported. For all studies comparing some form of psychological therapy with usual care or a waiting list that could be included in the meta-analysis, the psychological therapy resulted in less severe symptoms at end of treatment (SMD -0.34; 95% confidence interval (CI) -0.53 to -0.16; 10 studies, 1081 analysed participants). This effect was considered small to medium; heterogeneity was moderate and overall quality of the evidence was low. Compared with usual care, psychological therapies resulted in a 7% higher proportion of drop-outs during treatment (RR acceptability 0.93; 95% CI 0.88 to 0.99; 14 studies, 1644 participants; moderate-quality evidence). Removing one outlier study reduced the difference to 5%. Results for the subgroup of studies comparing CBT with usual care were similar to those in the whole group. Five studies (624 analysed participants) assessed symptom severity comparing some psychological therapy with enhanced care, and found no clear evidence of a difference at end of treatment (pooled SMD -0.19; 95% CI -0.43 to 0.04; considerable heterogeneity; low-quality evidence). Five studies (679 participants) showed that psychological therapies were somewhat less acceptable in terms of drop-outs than enhanced care (RR 0.93; 95% CI 0.87 to 1.00; moderate-quality evidence). When all psychological therapies included this review were combined they were superior to usual care or waiting list in terms of reduction of symptom severity, but effect sizes were small. As a single treatment, only CBT has been adequately studied to allow tentative conclusions for practice to be drawn. Compared with usual care or waiting list conditions, CBT reduced somatic symptoms, with a small effect and substantial differences in effects between CBT studies. The effects were durable within and after one year of follow-up. Compared with enhanced or structured care, psychological therapies generally were not more effective for most of the outcomes. Compared with enhanced care, CBT was not more effective. The overall quality of evidence contributing to this review was rated low to moderate. The intervention groups reported no major harms. However, as most studies did not describe adverse events as an explicit outcome measure, this result has to be interpreted with caution. An important issue was that all studies in this review included participants who were willing to receive psychological treatment. In daily practice, there is also a substantial proportion of participants not willing to accept psychological treatments for somatoform disorders or MUPS. It is unclear how large this group is and how this influences the relevance of CBT in clinical practice. The number of studies investigating various treatment modalities (other than CBT) needs to be increased; this is especially relevant for studies concerning physical therapies. Future studies should include participants from a variety of age groups; they should also make efforts to blind outcome assessors and to conduct follow-up assessments until at least one year after the end of treatment.

Plain-language summary: We rated the quality of current research as low to moderate. Fourteen out of the 21 studies focused on cognitive behavioural therapy, which is a specific form of talking therapy based on the idea that thoughts and thinking can influence emotions and behaviours. Cognitive behavioural therapy was more effective than usual care in reducing the severity of MUPS. For other types of therapy, we found only one or two studies giving insufficient evidence for conclusions. Cognitive behavioural therapy was no more effective than enhanced care provided by the person's doctor. No studies of physical therapy met the criteria to be included in the review. Talking therapies were acceptable to people and few people dropped out of the trials; however, this may not reflect real clinical practice as the study participants were people with somatoform disorders or MUPS who were willing to try talking therapies. In clinical practice, a high proportion of people may not be willing to accept these treatments. The review authors suggest that future high-quality trials should be carried out to find out more about which groups of people benefit most from cognitive behavioural therapy and how it can be most effectively delivered. They also suggest that more studies are needed of other talking therapies, and a particular focus should be on high-quality studies of physical therapies.