Studies have demonstrated the success of augmentation of antidepressant therapy with nonsteroidal anti-inflammatory drugs (NSAID) in decreasing depressive symptoms; however, little is known about the benefit of NSAID therapy on depressive symptoms.

This study pooled data from 5 postapproval trials, each trial a 6-week, multicenter, randomized, double-blinded, placebo-controlled, active-comparator, parallel-group study in subjects with active osteoarthritis. Subjects were randomized to placebo group, ibuprofen 800 mg 3 times daily or naproxen 500 mg twice daily group, or Celebrex 200 mg daily group. Apart from different ethnicities enrolled, these trials had identical study designs. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Outcomes measured were change in PHQ-9 score after 6 weeks of NSAID therapy and change in classification of depression with a PHQ-9 score ≥10 as a marker of depression.

There were 1497 patients included. Median PHQ-9 score was similar in all 3 groups at baseline and after 6 weeks of treatment. Multivariable regression analysis demonstrated a detectable effect in lowering PHQ-9 score in the ibuprofen or naproxen group (−0.31) and Celebrex group (−0.61) (P = .0390). With respect to the change in classification of depression, logistic regression analysis demonstrated a trend towards significant treatment effect of all NSAIDs compared with placebo.

Our analysis of pooled data from 5 postapproval trials shows that NSAID usage demonstrates a trend towards reduction of depression symptoms in patients with osteoarthritis based upon PHQ-9 scores. Future clinical trials should investigate this association with maximum dosage of drugs, increased treatment duration, and monitoring of social and environmental changes.