Why Painkillers Interfere with Anti-depressants

Patient Expert

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.

The study also suggested that Tylenol, an analgesic in a different class of pain meds, reduces the effectiveness of SSRIs, as well, though not as much as NSAIDs. (Opioid painkillers like Vicodin and Oxycontin weren't included in these studies.)

What do these results mean for me?

Scientists admit these results - from one mouse study and one human study - are very preliminary, mostly likely too much so to cause changes in the way doctors prescribe these medicines. But the investigators say that if studies continue to show this connection between NSAIDs and SSRI antidepressants, it could have a profound effect on the way both pain and depression are treated.

People who suffer from chronic pain could be prescribed other kinds of antidepressants such as tricyclic antidepressants or buproprion (Wellbutrin), which work on neurotransmitters in the brain, but not in the same way. Or, people with depression could be given other types of medications to treat their pain.

If you're one of the millions of people who take both an SSRI antidepressant and painkillers such as Tylenol, Advil, or aspirin regularly, you might want to discuss your use of these medications with your doctor. He or she will be able to best decide if you're on the most effective drug regimen possible to control both your depression and your pain.