Antidepressant Therapy for Unexplained Symptoms and Symptom Syndromes

Second, we did not perform blinded review of quality assessment. Blinded review has been demonstrated to produce lower and more consistent scores than open review.¹¹ Thus, our assessment of study quality may have overestimated the true quality of the evidence. The quality of the studies was not associated with effect size, making this issue less important as a potential bias in our estimate of the effect size.

Third, qualitative tallying can be misleading when describing the evidence, because the magnitude of the effect is not taken into account.¹¹⁵ Although such a method can be provocative, interpretation needs to be considered with caution, since the assessment of benefit was based on any outcome benefit. We felt that “vote counting” was still a useful way of describing the evidence, especially when describing this data in the context of the factors which might bias the results (study size, design, quality, country of study, and so forth; Table 3).

Finally, on the dichotomous outcome of improvement, we used any of 3 outcomes as a measure. Using multiple outcomes can increase the chances of a positive finding, and our summary odds ratio may overestimate the effect size. This was a systematic problem with this literature that did not regularly define primary outcome variables.

Conclusions

Though pooled quantitative data indicate substantial beneficial effect from antidepressants in multiple unexplained symptoms, there is a lack of high-quality evidence that systematically assesses this effect independent of depressive illness. Also, there were insufficient trials of SSRIs to make confident conclusions about the relative efficacy among different classes of antidepressants.

Future studies should include larger samples to allow for control of possible confounders; use parallel design studies to avoid the issue of possible carryover effect; examine for depression using standardized measures and track depressive as well as physical symptom effects; be of longer duration; test newer antidepressant classes, especially SSRIs (ie, determine whether all classes are equally effective); adhere to methodologic criteria of high-quality studies; and be located in community-based settings.

Recommendations for clinical practice

Physicians caring for patients with unexplained symptoms should focus their efforts on developing a therapeutic relationship, thoroughly exploring and treating any underlying depressive or anxiety disorder, and considering antidepressant therapy even if a depressive disorder is not evident.

Acknowledgment

This work was funded in part by the MacArthur Foundation Initiative on Depression in Primary Care. We would like to thank Robert J. Mohrman, librarian, for help with the database searches.