Antidepressants, OTC Painkillers Not a Good Combo

Antidepressants, known as selective serotonin reuptake inhibitors, or SSRIs, are some of the most commonly prescribed medications on the market today – and for good reason. It’s estimated that more than 20 million people in the United States suffer from depression.

At the same time, over-the-counter anti-inflammatory drugs like ibuprofen and aspirin also rank right up there in popularity, and in many instances, depressed patients are taking SSRIs in conjunction with these common painkillers – but this may not be the best idea, according to scientists at the Fisher Center for Alzheimer’s Disease Research at The Rockefeller University in New York City.

In a surprise discovery, they found that nonsteroidal anti-inflammatory drugs (NSAIDs) actually reduce the effectiveness of SSRIs.

“We have an interest in a protein called p11, because we’ve shown in previous publications from the laboratory that p11 plays a very important role in both depression and how antidepressants work,” Dr. Jennifer Warner-Schmidt, who co-led the study, told “Initially, our interest was to see whether there was an interaction between anti-inflammatory drugs and antidepressant drugs in how they regulated p11 expression.”

For the study, Warner-Schmidt and Dr. Paul Greengard, a Nobel laureate and director of the Fisher Center for Alzheimer’s Disease Research, treated mice with antidepressants, both in the presence and absence of anti-inflammatory drugs, and then analyzed how the mice behaved in “tasks that are sensitive to antidepressant treatment.”

“The work that we did in the animal models was using drugs like ibuprofen, aspirin and naproxen which are commonly taken by many people, and then we were able to take advantage of the human clinical work, where we were able to analyze, after the fact, a data set that was collected in human individuals that had depression, and we looked at whether the anti-inflammatory drugs or analgesic drugs attenuated their response rates,” Warner-Schmidt said.

In the end, they found the behavioral response to antidepressants in the mice was greatly inhibited by the anti-inflammatory drugs.

Warner-Schmidt and Greengard then turned their attention to humans, and took a closer look at the date from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study, which involved more than 4,000 depression patients aged 18 to 75 over a seven-year period.

“What we did, is that after the study had been completed, and Jennifer had found these results in the mice, we decided to look at that data that came from that Star*D trial, where they selected people with major depressive disorder,” Greengard said. “We just asked the question as to whether there was a difference based on the mouse data and whether there was a difference in outcome of those patients who said they had taken a concominant anti-inflammatory and those who said they had not taken any. It’s as simple as that, and then you look at what percentage of people have recovered on citalopram (Celexa) therapy when they reported a concominant use of an anti-inflammatory or an analgesic versus not reporting those.”

To break it down, in the absence of anti-inflammatory drugs, Warner-Schmidt and Greengard found 55 percent of patients responded to an antidepressant, while success rates dropped to approximately 40 percent for those patients who reported using anti-inflammatory drugs.

“That’s a big effect and we think that it might be much bigger than that because the placebo effect was not controlled in those studies,” Greengard said.

So what does this mean for the millions of people who are currently taking an antidepressant?

“What I think the implication here is really for anybody who is taking an SSRI who might be taking concominant anti-inflammatory medication, is that they should at least consider the possibility that if they’re not responding to the SSRI, that this could be one potential reason for it,” Warner-Schmidt said. “It’s certainly a first step in understanding the relationship between these two drugs, and it’s at least potentially of great clinical importance to suggest that for anybody taking an SSRI that an anti-inflammatory medicine may be interfering with their treatment response.”

Patients who are worried that they may be canceling out the effects of an antidepressant with their daily dose of aspirin or ibuprofen should talk to their doctor.

“We’re not in a position to recommend to doctors,” Greengard said. “The way we phrase it is very carefully. Depending on the intensity of the pain, they (doctors) might want to consider – if it’s low-level intensity – taking patients off the anti-inflammatories and the analgesics, and at least just do a trial period with the SSRI, or if that doesn’t seem appropriate and the pain level is higher, then have them on a non-SSRI antidepressant.”

Warner-Schmidt and Greengard, said these results could also have big implications for Alzheimer’s patients.

“Depression is a co-morbid illness in Alzheimer’s disease, and so a lot of these patients, many older people are depressed, virtually all of the people have arthritis – I’ve never met over the age of 65 who didn’t have some arthritic problems,” Greengard said. “What it means for the Alzheimer’s patient is that if they have pain that is very severe, then they should probably not be on an SSRI. If they have minor pain, then we think that the doctors may want to consider the possibility of taking them off the anti-inflammatory drug while they’re evaluating the antidepressant.”

According to the most recent statistics from the Alzheimer’s Association, an estimated 5.4 million Americans are living with the progressive disease. This number includes 5.2 million people who are 65 and older and another 200,000 people under the age of 65 who have younger-onset Alzheimer’s. Among these patients, an estimated 40 percent suffer from depression.

Warner-Schmidt and Greengard are currently trying to get funding for a follow-up study. The findings of the study will be published in the Proceedings of the National Academy of Scientists.

Click here for more information on the Fisher Center for Alzheimer’s Disease Research at The Rockefeller University.