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Amitriptyline has been used to treat chronic pain such as back pain.
Amitriptyline has been used to treat chronic pain such as back pain. Photograph: Yuri Arcurs/Alamy
Amitriptyline has been used to treat chronic pain such as back pain. Photograph: Yuri Arcurs/Alamy

‘Little evidence’ whether or not most antidepressants work for chronic pain

This article is more than 11 months old

Researchers say ‘studies not good enough’ to know whether medications work or not for pain

Antidepressants commonly used to treat chronic pain lack evidence as to whether or not they work, researchers have said, declaring the situation a global public health concern.

Chronic pain, typically defined as pain lasting three months or more, is a widespread problem affecting up to one in three people, with conditions ranging from osteoarthritis to fibromyalgia.

While exercise is often recommended, this is difficult for some patients, while there are concerns that opioids and other painkillers such as aspirin and paracetamol could do more harm than good.

Increasing numbers of patients are prescribed antidepressants to treat their pain, with hundreds of thousands in the UK estimated to be taking amitriptyline. Antidepressants affect chemicals known as neurotransmitters, which is how they are thought to relieve pain.

But a new Cochrane review, led by Prof Tamar Pincus, professor in health psychology at the University of Southampton, has revealed there is little evidence whether or not amitriptyline and many other common antidepressants work when it comes to tackling chronic pain.


“The fact that we don’t find evidence whether it works or not, is not the same as finding evidence that it doesn’t work,” she said. “We don’t know. The studies simply are not good enough.”

The review, conducted by Pincus and colleagues, looked at 176 randomised control trials involving nearly 30,000 patients.

Among other drugs the trials included amitriptyline, a tricyclic antidepressant, selective serotonin reuptake inhibitors such as fluoxetine and citalopram, and duloxetine – a serotonin-noradrenaline reuptake inhibitor. Patients experiencing mental health conditions, such as depression, were excluded from most trials.

The team found that many of the trials involved very small numbers of patients, making the results unreliable.

Only duloxetine – a drug with many industry sponsored trials – had enough evidence for the researchers to have even moderate confidence in their findings, with the drug found to have a small to moderate effect on substantial pain relief. The results also suggest a standard dose is as effective as higher doses.

Milnacipran, which belongs to the same class of antidepressants as duloextine, also showed a small effect at reducing pain, but the team said they had lower confidence in these results because there were fewer studies involving fewer people.

“Aside from duloxetine and milnacipran, we don’t have any confidence in the results from any other antidepressant in this review,” said Dr Hollie Birkinshaw, another author of the study from the University of Southampton.

The team add the average length of the various trials was just 10 weeks – despite patients often being prescribed antidepressants for six months.

“There was no reliable evidence on the safety of taking antidepressants for chronic pain, both short- and long-term,” the team said, adding it was also unclear whether antidepressants were effective at treating pain in the long term.

Pincus described the team’s findings as a global public health concern. But while she said that GPs should prioritise antidepressants for which there is the most evidence, she stressed that those taking amitriptyline should not stop their medications without consulting their doctor.

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