Anti-inflammatories May Help Ease Depression

Megan Brooks

October 21, 2014

Nonsteroidal anti-inflammatory drugs (NSAIDs) may help ease depressive symptoms, new research suggests.

Results of a meta-analysis show that the adjunctive use of NSAIDs was associated with improved antidepressant treatment response without an increased risk for adverse effects. In particular, add-on treatment with celecoxib (Celebrex, GD Searle LLC) improved antidepressant effects, remission, and response.

"Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects," the authors, led by Ole Kohler, MD, of Aarhus University Hospital, Risskov, Denmark, write.

The study was published online October 15 in JAMA Psychiatry.

Need for RCTs

"Compelling" evidence suggests a link between depression and inflammation. Several studies have investigated whether the use of anti-inflammatory agents might exert antidepressant effects, with conflicting results, the authors note.

To investigate further, they conducted a systematic review and meta-analysis of 14 relevant randomized, placebo-controlled trials that assessed the efficacy and adverse effects of anti- inflammatory drug therapy in a total of 6262 adults with depressive symptoms or depression.

The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms, compared with placebo, with a standard mean difference (SMD) of -0.34 (95% confidence interval [CI], −0.57 to −0.11).

The antidepressant effect was evident in studies that included patients with depression (SMD, −0.54; 95% CI, −1.08 to −0.01) and depressive symptoms (SMD, −0.27; 95% CI, −0.53 to −0.01).

The analyses favored anti-inflammatory treatment over placebo for both remission (odds ratio [OR], 2.73) and response (OR, 2.41).

Celecoxib as an adjunct to antidepressant treatment seemed most beneficial compared with placebo (SMD -0.82; 95% CI, -1.17 to -0.46, P < .001). Celecoxib add-on improved both remission (OR, 7.89; 95% CI, 2.94 - 21.17, P < .001) and response (OR, 6.59; 95% CI, 2.24 - 19.42; P < .001).

Cytokine inhibitors were studied in few trials and did not provide significantly better antidepressant treatment effects over placebo, the researchers note.

Neither NSAIDs nor cytokine inhibitors were associated with an increased risk for adverse effects, although not all studies reported adverse effects.

The investigators also note that most studies were small and of short duration, and most of the observed effect sizes were small to medium with high heterogeneity. The studies also had a "high risk of bias," which "tended to exaggerate treatment effects."

Nonetheless, their results provide "proof-of-concept concerning the use of anti-inflammatory agents in the antidepressant treatment regimen."

"Our findings emphasize the need for identifying subgroups that may benefit more from anti-inflammatory intervention, such as patients with elevated inflammatory markers or a somatic comorbidity. Specific agents, particularly celecoxib, showed promising results and should therefore be investigated in high-quality randomized clinical trials. Such trials should carefully report on adverse effects and include long-term follow-up," they write.

The authors report no relevant financial relationships.

JAMA Psychiatry. Published online October 15, 2014. Abstract

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