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Why Painkillers Interfere with Anti-depressants

Amy Tudor, Ph.D.

It’s long been known that there is a link between chronic pain and depression, but a new study suggests there may be a connection between the drugs that treat these two conditions as well. 

In a recent issue of the Proceedings of the National Academy of Sciences, scientists found evidence that non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduce the effectiveness of selective serotonin reuptake inhibitor antidepressants (SSRIs) such as Prozac, Lexapro, and Zoloft. In fact, NSAIDs – a class of painkiller that includes such commonly used drugs as aspirin, ibuprofen (Advil), and naproxyn (Aleve) – were associated with a 10 percent drop in depression remission rates, from 55 percent to 45 percent. What this means is that if you take NSAIDs and SSRI antidepressants together, there’s a 10 percent greater chance you’ll still suffer from depression, even if you’re taking a medication to treat it.

Meds send conflicting signals in the brain’s chemistry

But how can a drug designed to treat pain affect the way another medicine given to treat depression works?  The key appears to be on the drugs’ effects on the levels of immune-related substances called cytokines.

In two studies, scientists found that taking antidepressants raises levels of cytokines in a person’s body. These cytokines then boost the levels of a protein called p11. This protein makes more serotonin receptors on the surface of cells. Having more of these receptors makes it easier for them to interact with serotonin. Serotonin is the primary brain chemical that SSRIs are designed to affect. Increasing serotonin usually reduces depression.

But the researchers noted that when people took NSAIDs to reduce pain, the painkillers interfered with the production of these cytokines. This reduced the levels of p11 protein, which then reduced serotonin receptors on cells.  Thus, there were fewer serotonin receptors for the brain chemical to work on, and this kept the SSRI antidepressants from working at full strength.

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