By Pat Anson, PNN Editor

Most of the antidepressant drugs that are prescribed for chronic pain are either ineffective or the evidence supporting their use as pain relievers is weak, according to a new analysis published in The British Medical Journal (BMJ).

The use of antidepressants such as duloxetine (Cymbalta) and fluoxetine (Prozac) has doubled in recent years, with much of the increase due to their off-label prescribing to treat conditions such as fibromyalgia, neuropathy and back pain.

But in a review of 26 studies on the analgesic effects of antidepressants, Australian researchers found little evidence to support their use in pain management. The data on side effects was also weak, meaning the safety of antidepressants was also uncertain. Nearly half of the studies had ties or funding from the pharmaceutical industry.

“Recommending a list of antidepressants without careful consideration of the evidence for each of those antidepressants for different pain conditions may mislead clinicians and patients into thinking that all antidepressants have the same effectiveness for pain conditions. We showed that is not the case,” said lead author Giovanni Ferreira, PhD, from The Institute for Musculoskeletal Health at the University of Sydney.

“Some antidepressants were efficacious for some pain conditions; however, efficacy appears to depend on the condition and class of antidepressant. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain.”

Ferreira and his colleagues say no study provided high quality evidence on the effectiveness of antidepressants for any pain condition. 

But they did find moderate quality evidence supporting the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain, postoperative pain, fibromyalgia and neuropathic pain. Low-quality evidence suggested that SNRIs could be used for pain linked to breast cancer treatment, depression, knee osteoarthritis, and pain related to other underlying conditions.

The researchers say only low-quality evidence supports the use of selective serotonin reuptake inhibitors (SSRIs) for depression and pain related to other conditions; and tricyclic antidepressants (TCAs) as a treatment for irritable bowel syndrome, neuropathic pain, and chronic tension-type headaches. 

Antidepressants ‘Disappointing’ for Most Pain Patients

An accompanying editorial, also published in The BMJ, said the study adds to growing evidence that many medications prescribed for pain – not just antidepressants – are only modestly effective.

“Their findings suggest that for most adults living with chronic pain, antidepressant treatment will be disappointing. This is important given emerging concerns about increases in the prescribing of antidepressants and the challenges patients describe when trying to withdraw from treatment,” wrote Cathy Stannard, MD, UK National Health Service, and Colin Wilkinson, a pain patient and consultant at Centre for Pain Research, University of Bath.

“Clinicians continue to prescribe medicines for which the evidence is poor because they observe that some people respond to them, albeit modestly. But all medicines carry risk of harm and there are other, less potentially harmful options more likely to help people to live well with pain.”

Stannard and Wilkinson said exercise and physical activity might be better options than medication for some patients.

Ironically, a little over a year ago, the UK’s National Institute for Health and Care Excellence (NICE) released new guidelines that recommend antidepressants for adults with chronic primary pain, even when they are not depressed. NICE said antidepressants may help with quality of life, pain, sleep and psychological distress.

The NICE guideline is at odds with other studies that found antidepressants are minimally effective for back pain and osteoarthritis and often have adverse side effects. A common complaint of patients who take Cymbalta, for example, is how quickly they became dependent on the drug and have severe withdrawal symptoms when they stop taking it.