By Pat Anson, PNN Editor

Medical guidelines in the United States and United Kingdom may recommend antidepressants for treating chronic pain, but there is “no reliable evidence” that the medications actually work for that purpose, according to a new Cochrane review.

Cochrane reviews are considered the gold standard in medical research because they use robust methodology to gather good quality evidence, while dismissing poor quality research.

A team of UK researchers, led by scientists at the University of Southampton, spent two years examining 176 clinical trials involving nearly 30,000 patients who were prescribed antidepressants for pain. Among the drugs studied were fluoxetine (Prozac), sertraline (Zoloft), amitriptyline (Elavil), milnacipran (Savella), citalopram (Celexa), paroxetine (Paxil) and duloxetine (Cymbalta).

“Our review found no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for their safety for chronic pain at any point. Though we did find that duloxetine provided short-term pain relief for patients we studied, we remain concerned about its possible long-term harm due to the gaps in current evidence,” said lead author Tamar Pincus, PhD, a Psychology Professor at the University of Southampton.

“This is a global public health concern. Chronic pain is a problem for millions who are prescribed antidepressants without sufficient scientific proof they help, nor an understanding of the long-term impact on health.”

In the United States, duloxetine is FDA-approved for fibromyalgia, diabetic neuropathy and musculoskeletal pain. The recently updated CDC guideline recommends that duloxetine and other SNRI antidepressants be used for fibromyalgia and neuropathy, because they provide “small to moderate improvements in chronic pain and function.”

The UK’s National Institute for Health and Care Excellence (NICE) guideline goes even further, stating that antidepressants are better than opioids and other analgesics in treating fibromyalgia, chronic headache, Complex Regional Pain Syndrome (CRPS), musculoskeletal pain and other types of “primary chronic pain” for which there is no known cause.   

The authors of the Cochrane review say regulators in the US and UK should reconsider their recommendations.

“We are calling on governing health bodies NICE and the FDA to update their guidelines to reflect the new scientific evidence, and on funders to stop supporting small and flawed trials. Evidence synthesis is often complex and nuanced but the evidence underpinning the use of these treatments is not equivalent, so current treatment modalities are hard to justify,” said co-author Gavin Stewart, PhD, a statistician at Newcastle University.

Amitriptyline is one of the most commonly prescribed antidepressants for chronic pain in the world. In the last year, around 10 million prescriptions for amitriptyline were given to patients in England for pain, about twice the number prescribed for depression. Many other antidepressants are also prescribed “off-label” for pain, despite limited evidence to support their use.

“Though previous investigations show that some antidepressants might relieve pain, there has never been a comprehensive study examining all medications across all chronic conditions – until now,” said co-author Hollie Birkinshaw, PhD, a Research Associate at the University of Southampton.

“The only reliable evidence is for duloxetine. Adopting a person-centered approach is critical to treatment and, when patients and clinicians decide together to try antidepressants, they should start from the drug for which there is good evidence.”

The reviewers say duloxetine was the highest-rated antidepressant for treating fibromyalgia, musculoskeletal and neuropathic pain. Standard doses of duloxetine were just as effective as higher ones. Milnacipran was also effective at reducing pain, although the evidence was weaker.

“We simply cannot tell about other antidepressants because sufficiently good studies are not available – but it does not mean that people should stop taking prescribed medication without consulting their GP,” said Pincus.

A common complaint of patients who take duloxetine is that it makes them dizzy and nauseous. Many quickly become dependent on the drug and then have severe withdrawal symptoms when they stop taking it.

Several previous studies have also raised questions about using antidepressants for pain. A recent review of over two dozen clinical trials by Australian researchers found little evidence to support the use of antidepressants in pain management. Nearly half of the trials had ties or funding from the pharmaceutical industry.