transparent man's head high lighting the brainIf you’re taking a selective serotonin reuptake inhibitor (an SSRI antidepressant) that doesn’t seem to be working very well and you take nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, to relieve pain, that NSAID may be the reason why your SSRI isn’t working.

Recently Paul Greengard PhD published a report in an online journal that strongly suggests that treatment with NSAIDs may reduce the antidepressant activity of SSRIs. Their research is based on the theory that depression is at least partially related to the body’s inflammatory responses. This is called the cytokine hypothesis and is based on observations that some chemicals released as part of inflammation – cytokines – are involved in regulating neurotransmitters such as serotonin.

It has been found that SSRIs increase levels of particular cytokines and a protein known as p11, which is also related to the cytokine theory of depression. NSAIDs abolish those effects of the SSRIs.

This study of the chemistry of SSRIs and NSAIDs helps outline the possible mechanism behind findings in the STAR*D study – a major study of people with depression – that showed NSAID use was associated with poorer response to SSRIs when they were taken with NSAIDs.

The researchers state that based on the combination of clinical and biochemical studies that now show such a strong negative relationship between these two medicines, doctors should carefully consider the risks and benefits of using NSAIDs in patients being treated for depression.

SSRIs include Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Celexa (citalopram), Lexapro (escitalopram), and Luvox (fluvoxamine).

NSAIDs include aspirin, ibuprofen, and celecoxib (Celebrex), to name only a few of the more common NSAIDs.

If you take SSRIs and NSAIDs you should not stop either medicine, but this is something to discuss with your doctor. The article doesn’t specifically mention whether using NSAIDs occasionally for a headache poses a problem, but the study is based on chronic exposure of cells to the anti-inflammatory agent, so I would expect that this is more of a concern for people who are taking NSAIDs regularly for more long-term pain management. Some people, however, don’t realize how often they’re taking medicines for pain – and it’s something to consider if you’re not having a positive response to your antidepressant.

Photo by Pedro Vera, available under a Creative Commons attribution license.



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    Last reviewed: 26 Jul 2011

APA Reference
Fink, C. (2011). NSAIDs May Reduce Effectiveness of SSRIs. Psych Central. Retrieved on October 31, 2014, from


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Candida Fink, M.D. and Joe Kraynak are authors of
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