Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce suicidal ideation and depression

Abstract

Background: Neuroinflammation has been implicated in depression. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in treating animal models of depression, alone or with antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. In the current study, we evaluated the effect of NSAIDs on suicidal ideation and depression.

Methods: We used data from MedWatch, the Food and Drug Administration (FDA) Safety Information and Adverse Event Reporting Program. Machine-readable data from MedWatch, including adverse drug reaction reports from manufacturers, are part of a public database. We used the online tool OpenVigil 2.1 to query the database. OpenVigil calculates proportional reporting ratios (PRRs) from adverse drug reaction reports to determine whether the combination of drug and adverse event are related.

Results: Significantly less suicidal ideation was reported in patients treated with ibuprofen, naproxen, celecoxib, or aspirin (NSAIDs) compared to acetaminophen (a non-NSAID). Significantly less depression was reported in patients treated with naproxen or aspirin compared to acetaminophen, but significantly more depression in patients treated with celecoxib compared to acetaminophen. Ibuprofen in women but not men was associated with significantly less depression.

Conclusion: Only 1-2% of an oral NSAID dose reaches the brain. We have proposed a new route of administration for drugs to treat neuropsychiatric illnesses: Trans-spinal delivery by transdermal patch over the back-of-neck/cervical spine. The drug would diffuse from the patch through the intervertebral spaces, penetrate the dura, and enter the CSF, where it would reach the brain. NSAIDs might be valuable agents for treating depression and suicide, as is supported by this study, especially if they can reach the brain at a higher concentration. Further studies of NSAIDs in these conditions are warranted.