At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole K ö hler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications ( JAMA Psychiatry 2014;71:1381-91 ). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.

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