Following the largest ever systematic review of the data around antidepressants and chronic pain, patients can now receive more effective drugs prescribed at a lower dosage
Result discovery
To help patients live with ongoing pain, GPs commonly prescribe drugs for pain reduction. The National Institute for Health and Care Excellence (NICE) recommends antidepressants, the most common being amitriptyline with over 15 million prescriptions a year – despite there being no agreed-upon explanation as to how antidepressants work to alleviate pain.
In the absence of clear and agreed understanding as to the effectiveness of the drugs, Southampton scientists carried out the largest ever systematic review of the data around antidepressants and chronic pain. Partnering with Cochrane, a global network which sets the gold standard for independent and transparent health data reviews, the team used network meta-analysis, a technique which allows evidence across studies to be compared simultaneously. Over the course of two years, they scrutinised findings from 176 trials, which included almost 30,000 patients taking 27 different antidepressants.
The results were shocking. “In effect, the data is so poor that we cannot claim to know anything about most of the drugs. The trials were so small that we can’t trust them. None of the trials for amitriptyline reached the size threshold that we and Cochrane required for reliability, which is at least 200 people in each arm of the study,” says Professor Tamar Pincus, Dean of the Faculty of Environmental and Life Sciences and project lead.
By contrast, the results for the drug duloxetine were stronger, with trials being much larger and extended across people with three different types of common pain condition: fibromyalgia, neuropathic and musculoskeletal pain. The effect was similar across the three groups, and importantly, the same whether a regular dose of 60 milligrams or a high dose of 120 milligrams was prescribed. The findings demonstrate that duloxetine can be used more widely, and reduce pain by up to 50 per cent while being prescribed at a lower dose, with fewer side effects.
Changing guidelines
As a result of the study, changes have been made to the clinical summary, the advice on best practice which many primary care practitioners will access. Duloxetine has been moved to the top of the list of antidepressants, making it more likely to be the first choice for GPs. The advice also explicitly states that a 60 mg dosage is equally effective, leading to fewer people taking more than necessary.
Bodies in Scotland and Belgium are already working to incorporate the team’s findings, and there is belief that NICE will respond more fully at the next review cycle. “Without a doubt, as time goes on, our review is going to impact on guidelines,” says Tamar.
We’ve also highlighted the need for further, larger studies – the University of Southampton could be well-positioned to carry out a big amitriptyline trial in the near future.”
Professor Tamar Pincus, Dean of the Faculty of Environmental and Life Sciences
Beyond that, the researchers believe that the study is indicative of the need for a big-picture overhaul of the current approach to chronic pain treatment. They have since developed an intervention to tackle pain-related distress in people living with chronic pain, to avoid unnecessary and potentially harmful use of medication. Another qualitative study is also underway, around the experiences of people both taking and coming off anti-depressants. Chronic pain affects around one in five people in the UK.
