Around one-third of people globally live with chronic pain - pain experienced for more than three months - and millions of people are prescribed antidepressants to relieve the condition.
However, a new review of prior research published Tuesday has found that most antidepressants used to relieve chronic pain are being prescribed without sufficient reliable evidence of their effectiveness. What's more, potential harms haven't been well studied.
A two-year study by the nonprofit group Cochrane found that only one antidepressant, duloxetine, was effective for short-term pain relief based on the available evidence. Cochrane is an international collaboration of researchers that produces the Cochrane Library, which includes a database of systematic summaries addressing key questions in health care.
Sold under the brand names Irenka and Cymbalta, duloxetine is a serotonin and norepinephrine reuptake inhibitor, or SNRI, and also boosts levels of the feel-good neurochemical dopamine.
"This is a global public health concern," said lead author Tamar Pincus, a professor and chronic pain researcher at the University of Southampton in the United Kingdom.
"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."
No evidence for effectiveness of commonly prescribed drug
The review included 176 studies with a total of 28,664 participants and looked at 25 different antidepressants. The studies mainly investigated three types of chronic pain: fibromyalgia, nerve pain and musculoskeletal pain.
The average length of the study was 10 weeks, and the studies were randomised controlled trials - regarded as the gold standard in medical research. Seventy-two of the studies were funded by pharmaceutical companies.
The most commonly prescribed antidepressant for chronic pain globally was amitriptyline, the study said. Sold in the United States under the brand names Elavil and Vanatrip, the antidepressant was approved in 1961 by the US Food and Drug Administration to treat depression in adults. The medication has significant side effects, so it is not commonly used for depression, but is prescribed to treat migraines and chronic pain such as diabetic neuropathy.
However, the authors found most of the studies on amitriptyline's effectiveness were small and the evidence was not reliable.
Milnacipran, which is approved by the FDA for fibromyalgia, was also effective at reducing pain, the review found, but the scientists were not as confident about this drug compared with duloxetine due to limited studies with few people.
Anyone taking antidepressants for chronic pain relief should speak to their doctor before stopping their medication due to concerns over the new report, the authors stressed.
Pain isn't uniform
Antidepressants are thought to help with pain because the bodily systems that regulate mood and pain overlap, explained Ryan Patel, a research fellow studying chronic pain at the Wolfson Centre for Age-Related Diseases at King's College London.
He said the key question for researchers to answer was not whether antidepressant drugs were effective for treating pain but "for whom are antidepressants effective?"
"Even when the cause of chronic pain is the same, the biological changes that occur in the nervous system are varied and so it is no surprise that pain presents differently from person to person, and not everyone will respond to the same drugs," said Patel, who wasn't involved in the review.
"What this comprehensive analysis demonstrates is that when clinical trials are designed poorly under the assumption that everyone's experience of pain is uniform, most antidepressants appear to have limited use for treating chronic pain," Patel added in a statement.
Long-term use needs study
Even for the antidepressant duloxetine, there was no research looking at long-term use of the drug, the review found.
"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," Pincus said.
The report said future research should address any unwanted effects of using antidepressants for chronic pain, noting that the existing data on this was "poor."
"It (duloxetine) does look really good at the moment for short term pain relief, but I want to emphasise that patients aren't prescribed duloxetine or any antidepressant for three weeks, four weeks, six weeks, they're prescribed it for six months. So it's really shocking that we don't have any evidence for long term use of even duloxetine," Pincus said.
Dr Cathy Stannard, the clinical lead for the UK National Institute for Health and Care Excellence (NICE) guideline for chronic pain, and a pain specialist for NHS Gloucestershire's Integrated Care Board in the UK, said that it was important to emphasise the social and psychological influences on how people experience pain and the importance of a patient's relationship with their doctor.
"There is good evidence that for people with pain, compassionate and consistent relationships with clinicians remain the foundations of successful care," Stannard, who wasn't involved in the research, said in a statement.
"Research shows that what people want most is a strong, empathic relationship with their care provider. They want time to discuss what matters to them and they want easy access to support and to be partners in their care."
Non-pharmaceutical interventions, such as support with mobility, debt management, trauma and social isolation, were also likely to help people living with pain, she added.
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