Limited evidence suggests that co-morbid chronic physical illness may not increase risk for recurrence in depression


There is a widespread clinical presumption that people who have both major depressive disorder (MDD) and a co-morbid chronic physical illness represent a ‘double trouble’ group. This leads to the expectation that the depression prognosis for these people would be poor with increasing likelihood of recurrence.

Evidence supports the view that depression is prevalent among people with a physical illness, more so than those without a physical illness. American Psychiatric Association recommends some form of maintenance treatment for depression indefinitely for people with a chronic illness and depression.

This systematic review set out to examine whether chronic physical illness is indeed a risk factor for recurrent episodes of MDD.


Research tells us that depression is prevalent among people with a physical illness

Research tells us that depression is prevalent among people with a physical illness

The authors selected heart diseases, gastrointestinal diseases, diabetes, rheumatoid arthritis, asthma, HIV and cancer as the chronic physical diseases for this review as they feature heavily in clinical practice guidelines.

The authors included studies that had a longitudinal measure of depression (based on established interview or standardised scales) with a follow-up of at least 6 months and that had data from patients with or without a chronic illness at the same measurement intervals.

Biomedical databases (PubMed, EMbase, PsycINFO) and additional sources (including reference lists) yielded 3,450 articles, 3,121 of which were excluded as they did not include a group without a physical illness. The review was performed on 4 articles that looked at depression recurrence in patients with and without co-morbid physical illness (one study’s participants were children). The total sample size was 2,010 with 694 participants with one or more physical illness.


The authors calculated Risk Ratios (RR) and 95% Confidence Intervals (CI) for each study.

  • The results indicated that the presence of a chronic physical illness did not increase the risk of major depression episode recurrence
  • Only in the case of one study, at two year follow-up the RR was higher than 1 indicating that more risk for depressive recurrence among chronically ill (RR=1.37, 95% CI, 0.78-2.41), although it’s important to note the wide confidence interval around this result.

The authors conducted a quality assessment of the articles and concluded that there were methodological problems in the studies. Some of these included lack of use of established criteria for depression assessment in follow-up, different follow-up times and treatment received, type and assessment of physical illnesses, and unequal sizes of physical illness and reference groups.


We need more evidence before we can conclusively answer this question

We need more evidence before we can conclusively answer this question

This review suggests that for the supposed ‘double trouble’ group – those with a major depressive disorder and a chronic physical illness, there is no indication of heightened risk of depression recurrence. However, there is a caution: the number of studies that could provide an answer is very limited.

The evidence from this systematic review has implications for current clinical guidelines. American Psychiatric Association recommends some form of long-term maintenance treatment for people with depression and co-morbid physical illness. The limited evidence emerging from this systematic review shows that the presumption that this group of people represent high risk for depression recurrence may not be correct.

Unsurprisingly, the authors call for additional longitudinal studies that examine the impact of chronic physical illness on the course of depression. They also identify other questions that remain still unanswered. What’s the impact of progression of physical illness on depression? If the chronic illness improves, will depression improve too? The authors also recommend outcomes other than depression recurrence such as quality of life and sick leave from work for future research.

The review’s strength lies in the fact that inclusion criteria such as the use of established diagnostic criteria for depression ensures that studies in the review have reliable measures. However, the review included a study done on children whereas the other three were adult-based. It is not clear why there were no exclusion criteria on the basis of age and this difference in the studies reviewed is not explained. Overall, although the review suggests that there was no indication of heightened risk for depression recurrence among patients with co-morbid physical illness, the evidence relied on only a handful of studies. As the cliché goes, more research is required!


Kok GD, Bockting CLH, Burger H, Hannig W, Pijnenborg GHM, et al. (2013) Double Trouble: Does Co-Morbid Chronic Somatic Illness Increase Risk for Recurrence in Depression? A Systematic Review. PLoS ONE 8(3): e57510. doi:10.1371/journal.pone.0057510

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