Review article
Negative association of concomitant physical symptoms with the course of major depressive disorder: A systematic review

https://doi.org/10.1016/j.jpsychores.2009.11.009Get rights and content

Abstract

Objective

The prognosis of depression greatly varies among patients, and the physical symptoms that often accompany depression may predict treatment resistance and a worse outcome. If so, this may have important clinical implications. The aim of this systematic review was to explore the association of concomitant physical symptoms with the outcome of major depressive disorder (MDD).

Methods

Systematic review: Medline, Psychinfo, and the Cochrane Library were searched for prospective, cross-sectional, and retrospective studies, and also for open-label trials and randomized controlled trials. The risk of bias assessment and data extraction were performed in duplicate. A qualitative best-evidence synthesis was performed, based on the number of studies reporting on the association between physical symptoms and the course of MDD, the consistency of the results, and the methodological quality. The findings were reported according to the PRISMA guidelines.

Results

Nine studies met the inclusion criteria. Although the design, outcome measures, and data presentation varied too much to make statistical pooling possible, the best evidence synthesis resulted in strong, consistent evidence for a negative association between physical symptoms and the course of MDD.

Conclusion

This systematic review shows a negative association of concomitant physical symptoms with the course of MDD. The effect might be considerable, but the number of studies addressing this topic is small and there was a wide variation in the study designs and outcome measures. More research is needed.

Introduction

The Global Burden of Disease Study, carried out by the WHO, reports that major depressive disorder (MDD) is expected to be the second leading cause of disability-adjusted life-years in 2020 [1]. Both psychological and pharmacological interventions are effective in the treatment of MDD, but like in other fields of medicine, efficacy trials where it is possible to control certain conditions, do not always produce the same results as effectiveness trials in real world settings [2]. Results from the STAR*D study, for instance, show that remission rates in response to treatment with a selective serotonin reuptake inhibitor (SSRI) are as low as 26.6% in primary care [3]. These rates improve after subsequent treatment steps, but remission is not easily achieved [4]. This might lead to unnecessary suffering and high costs for society [5], [6].

MDD may be difficult to treat in everyday practice, as a result of concomitant physical symptoms interfering with the course, or because depressed patients who experience many physical symptoms may be less motivated to undergo treatment. This is an important subject for study, in view of the frequent co-occurrence of physical symptoms and MDD. Studies in primary care, for instance, have found that up to 70% of MDD patients only report physical symptoms when first presenting to a general practitioner [7]. Moreover, a recent study [8] reported that it is 4.43 times more likely for a depressed patients to have a somatoform disorder than for patient who is not depressed (confidence interval: 2.73–7.19).

Examples of symptoms that often co-occur with MDD are pain, fatigue, disturbed sleep, indigestion, dizziness, and fainting [9], [10]. The more of these symptoms a patient experiences, the greater the probability that he or she is also suffering from a depressive disorder [9], [10]. The importance of physical symptoms in patients suffering from MDD will also be recognized by clinicians, many of whom find patients with physical comorbidity difficult to treat. A recent systematic review provided evidence that pain predicts a longer time to remission in patients suffering from MDD [11].

To our knowledge, evidence with regard to the prognostic effect of the wider spectrum of concomitant physical symptoms—not restricted to pain—on the course of MDD has not yet been reviewed. Identifying factors that may predict treatment resistance or poor outcome are important, both for the education of patients and the selection of appropriate treatment. We therefore conducted a systematic review of studies that assessed the associations between physical symptoms and the prognosis of MDD. The association in terms of prognostic value in cohort studies, as well as the modification of treatment effect in trials can provide valuable information about this topic. Both types of studies were therefore included.

Section snippets

Information sources and eligibility criteria

The search was performed in Medline, Psychinfo, and the database of the Cochrane Collaboration. The search focused on retrospective and prospective designs, as well as on open-label trials and randomized controlled trials. Studies had to meet the following criteria in order to be included:

  • 1.

    At baseline, an assessment had to be made to determine whether patients were suffering from MDD. There was no restriction as to how MDD was diagnosed. At follow-up, an assessment had to be made about the

Study selection and characteristics

The searches in Medline, Psychinfo, and the Cochrane Library yielded 2327 hits. All of the abstracts were written in a language that could be interpreted by the authors. Nine studies met the inclusion criteria.

The results of the searches are shown in a flowchart (Fig. 1) that was designed according to the PRISMA guidelines [19].

The characteristics of the studies that were included are presented in Table 1.

Risk of bias

The results of the risk of bias assessment are presented in Table 2.

Initial agreement

Summary of evidence

All studies included in this systematic review indicated a negative effect of physical symptoms on the prognosis of MDD. Based on the consistency of this finding across the available studies, the strength of the associations found, and the quality of the studies, the overall level of evidence for this association appears to be strong. The overall association of physical symptoms was sub-divided in two types of association: Type A, which refers to the association between physical symptoms and

Acknowledgments

This project was funded by the “Innovatiefonds Zorgverzekeraars” (Foundation for Innovation of the Health Care Insurances in the Netherlands).

The authors gratefully acknowledge the help received from Ingrid Riphagen in designing the search strategy.

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