NMA: Nonprescription Medicines Academy

NSAID Use May Lead to Poorer Antidepressant Outcomes

December 14th, 2012

The results of a pharmacovigilance study support an association between nonsteroidal anti-inflammatory drug use and poorer antidepressant outcomes in major depressive disorder, but some of the observed effect may be attributable to confounding.

Can nonsteroidal anti-inflammatory drugs (NSAIDs) interfere with antidepressant response? Possibly, according to a pharmacovigilance study using data from a large health care system and a reanalysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

A previous study had suggested that NSAID-treated patients in the STAR*D cohort with major depression were less likely to achieve remission with citalopram than patients who were not treated with NSAIDs. However, because NSAID use in the STAR*D cohort was not randomly assigned, the risk of confounding was substantial. The current study was designed to confirm an association between NSAID use and treatment resistance in an independent population-based cohort, as well as to better characterize the potential confounding effects of medical comorbidity in the STAR*D study.

The independent cohort encompassed 1,528 outpatients in a New England health care system who had a major depressive disorder treated with antidepressant agents. Patients were considered to be NSAID-exposed if they received at least one documented prescription during the classified antidepressant treatment period. The primary analysis compared antidepressant response between patients with chronic NSAID use and patients unexposed to NSAIDs. A secondary analysis distinguished among NSAIDs, cyclooxygenase-2 inhibitors, and salicylates.

The majority of patients in the independent cohort (1,245; 81%) were exposed to NSAIDs or NSAID-like medications. NSAID exposure was associated with a significantly greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (OR, 1.55; 95% CI, 1.21–2.00). This association was apparent in the NSAIDs-only group but not among patients using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors or salicylates). Similar results were obtained in the reanalysis of STAR*D data. Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding. In the independent cohort, association with outcome was no longer significant in fully adjusted models; more modest effects were seen in the STAR*D cohort.

The authors concluded that the results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding.

Am J Psychiatry. 2012;169:1065-72.