How effective are antidepressants for pain?

An Australian study published in The BMJ has advocated for a ‘nuanced’ approach to prescribing antidepressants for chronic pain, after the overview of systemic reviews found evidence of efficacy in only 11 of the 42 comparisons.
 
According to the research, the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine was found to be effective for the largest number of pain conditions, including back pain, fibromyalgia, neuropathic pain and knee osteoarthritis.
 
However, the University of Sydney researchers say evidence is lacking for other cotricyclic antidepressants such as amitriptyline, which are the most commonly used in clinical practice for chronic pain.
 
The NHMRC-supported research also showed there was no evidence or inconclusive evidence for fluoxetine, venlafaxine, mirtazapine for a range of conditions such as irritable bowel syndrome, functional dyspepsia, fibromyalgia and phantom limb pain.
 
It comes after the UK’s National Institute for Health and Care Excellence (NICE) 2021 guidelines for chronic pain management in primary care recommend against using pain medicines but support antidepressants, specifically listing citalopram, duloxetine, fluoxetine, paroxetine, sertraline and amitriptyline as options.
 
Lead author of the Australian research, Dr Giovanni Ferreira from the Faculty of Medicine and Health, Sydney School of Public Health, told newsGP recommending them like this without enough evidence could be misleading.
 
‘What our research has shown is that prescribing antidepressants for chronic pain requires a careful consideration of the evidence for each antidepressant and pain condition individually,’ he said.
 
‘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.’
 
Meanwhile, Chair of RACGP Specific Interests Pain Management Dr Milana Votrubec, told newsGP she has concerns over conflicts of interest related to industry-funded research in this area – an issue also cited in the BMJ paper.
 
‘[There is] not enough research in this field that isn’t biased by a conflict of interest,’ she said.
 
‘The most telling aspect of this paper falls under the heading, “Implications for clinicians and future research”, which concludes with “caution is needed in interpreting our findings, as 45% of the trials forming the body of evidence for this review had industry ties”.’
 
She says this point is particularly relevant to evidence regarding SNRIs, which represented 68% of trials identified as having industry ties and thus having a potential source of bias.
 
But while Dr Votrubec believes it is important to have research unconnected with industry influence, she says it can be hard to achieve.
 
‘[It’s] impossible to research without funding,’ she said.
 
‘However, the NHMRC independent funding body in Australia has some fairly narrow criteria for inclusion. As this paper is specifically looking at medications for use in pain management, it’s understandable that 45% of the research papers were funded by industry.’
 
The review examined 26 systematic reviews from 2012–22 and included over 25,000 participants. Data included eight antidepressant classes and 22 pain conditions including back pain, fibromyalgia, headaches, postoperative pain, and irritable bowel syndrome.
 
As antidepressants are commonly prescribed for pain comorbid symptoms such as brain fog, fatigue and myalgias, Dr Ferreira said it is important to highlight that there is low-level evidence for duloxetine in this domain.
 
‘We have found some low certainty evidence that SNRIs [such as] duloxetine and SSRIs [such as] paroxetine were effective in people with depression and comorbid pain,’ he said.
 
‘It is an area worth investigating given the high prevalence of pain and comorbid depression and vice-versa.’
 
Co-author Dr Christina Abdel Shaheed also told newsGP that just because there is not enough evidence for some antidepressants’ efficacy in pain it does not mean they are useless.
 
‘“Evidence of no benefit” is a very different proposition to “no evidence of benefit”,’ she said.
 
‘This review found a surprising paucity of evidence in the field, warranting more research given the increase in prescribing of antidepressants for chronic pain globally.’
 
Dr Ferreira agrees more data is required.
 
‘There is definitely a need for more research in the field,’ he said.
 
‘One condition that would benefit for more research is sciatica. While pharmacological treatments are a core component of the clinical management of sciatica, most commonly used pain medicines for sciatica are not effective or of unclear value.
 
‘Antidepressants may be effective for chronic sciatica, but the evidence is inconclusive.’
 
Dr Ferreira says his team’s research provides an up-to-date review of antidepressants as part of a holistic approach to pain management.
 
‘This review, for the first time, brings together all the existing evidence about the effectiveness of antidepressants to treat chronic pain in one comprehensive document,’ he said.
 
‘Treatment of chronic pain requires a multidisciplinary approach, and both pharmacological and non-pharmacological treatments have a role.’
 
While antidepressants are quicker to start and cheaper than other treatments such as physiotherapy, exercise physiology and psychology, Dr Ferreira says whether or not they are a considered a ‘quick fix’, pain amelioration is the underlying imperative.
 
‘We need to focus on finding and implementing effective treatments that will improve the lives of millions of people in Australia who live with chronic pain,’ he said.
 
‘Some pain medicines may have a role in pain management, but they need to be considered as only part of the solution.
 
‘For some pain conditions, exercise, physiotherapy, and lifestyle changes may also help. [Patients can] speak to their health professional to learn more about what alternatives might be appropriate.’
 
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