Commonly used painkillers such as ibuprofen and acetylsalicylic acid can undermine the effectiveness of antidepressants, new research suggests.
The study could explain, at least in part, why many patients - particularly those with Alzheimer's disease - respond poorly to drug treatments for depression.
"Our results may have profound implications for patients, given the very high treatment-resistance rates for depressed individuals taking SSRIs [selective serotonin reuptake inhibitors]" said Jennifer Warner-Schmidt, a research associate in the laboratory of molecular and cellular neuroscience at Rockefeller University in New York City and co-author of the paper.
The study, published on Tuesday in the medical journal Proceedings of the National Academy of Sciences, examined the interaction between the SSRI class of antidepressants and a class of painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs).
SSRIs include prescription drugs such as Zoloft, Paxil and Prozac. NSAIDs include over-the-counter medications such as Aspirin and Advil and prescription drugs such as Celebrex and Voltaren.
The research was done in two stages.
First, researchers examined a protein known as p11, a commonly used marker for depression. P11 appears to make brain cells more sensitive to the positive mood-enhancing effects of serotonin.
Using laboratory mice, they found that SSRIs bolstered p11 while NSAIDs suppressed p11, meaning that the benefits of the antidepressants were largely offset by the effects of the painkillers.
Next, the research team tested the theory in humans.
They found that patients who took SSRIs responded 54 per cent of the time to the drug treatment for depression. But if the patients also took an NSAID, the response rate fell to just 40 per cent.
Paul Greengard, director of the Fisher Center for Alzheimer's Disease Research at Rockefeller University (and a Nobel Prize winner), said the findings are particularly pertinent to patients with dementia, who are treated routinely for depression and painful conditions such as arthritis.
"Many elderly individuals suffering from Alzheimer's disease also have arthritic or related diseases and as a consequence are taking both antidepressant and anti-inflammatory medications," Dr. Greengard said. "Our results suggest that physicians should carefully balance the advantages and disadvantages of continuing anti-inflammatory therapy in patients being treated with antidepressant medications."
He said that while the biological mechanism for the interaction between the two drugs is not entirely clear, it is easily avoidable by prescribing another type of painkiller.
There are more than 23 million prescriptions for SSRIs annually in Canada, and sales of the drugs exceed $1-billion a year, according to IMS Brogan, a private company that tracks prescription-drug sales.
In addition to depression, SSRIs are used to treat obsessive-compulsive disorder, anxiety disorder and hot flashes during menopause.
There are other drug interactions involving SSRIs that have been established. For example, research has shown that the benefits of tamoxifen, a drug used to treat breast cancer, can be nullified if a woman is also taking Paxil.