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PainFeb 1, 2023

Establish 'compassionate and consistent relationships' with people living with pain, clinicians told

All medicines carry an inherent risk and other options are more likely to help people ‘live well with pain’, according to two UK-based experts on the topic.

In an editorial appearing in the latest issue of The BMJ, Cathy Stannard and Colin Wilkinson say there is ‘good evidence’ for the benefits of group exercise, delivered by appropriately skilled instructors.

‘Exercise and physical activity have many other health and wellbeing advantages in addition to useful improvements in symptoms for people with pain,’ they suggest.

Dr Stannard, a former consultant in pain medicine, is based at NHS Gloucestershire Integrated Care Board, while her co-author, who ‘lives with pain’, is based at the University of Bath’s Centre for Pain Research. Both have helped to produce guidelines on pain published by the National Institute for Health and Care Excellence in recent years.

The pair comment on a research paper appearing in the same edition of The BMJ, which presents an overview of the effectiveness, safety, and tolerability of antidepressants for pain according to condition. The authors of the research paper acknowledge that while some antidepressant drugs can be effective in some pain conditions, most are either ineffective or lack conclusive evidence for their efficacy.

Photo Credit: Shutterstock
Antidepressant use doubled in OECD countries in the first 15 years of this century


'Compassion' is key

Dr Stannard and Mr Wilkinson state that clinicians continue prescribing medicines – even when the evidence is poor – because they see that some patients respond to them, albeit modestly.  But they argue that compassionate and consistent relationships with clinicians represent the cornerstones of successful interventions. 

Studies must involve people living with pain to ensure that pain research is meaningful to them and helps them and their clinicians reach shared decisions about treatments, they conclude.

Link to use of antidepressant 'doubling' in 15 years

The research paper, written by a team led by Giovanni Ferreira from the University of Sydney (a physiotherapist by background), states that the use of antidepressants doubled in OECD countries from 2000-2015. Their ‘off-label’ (or unapproved use) to treat common pain conditions – including fibromyalgia, persistent headaches and osteoarthritis – is thought to have contributed to this increase.

After searching databases for systematic reviews comparing any antidepressant with placebo for any pain condition in adults, Dr Ferreira and his colleagues found 26 eligible evidence reviews published from 2012 and 2022 involving 156 separate trials and more than 25,000 participants.

These reviews reported on the effectiveness of eight classes of antidepressant covering 22 pain conditions (42 distinct antidepressant versus placebo comparisons). Almost half (45 per cent) of the trials in these reviews had ties to industry.

Some antidepressants were efficacious for some pain conditions; however, efficacy appears to depend on the condition and class of antidepressant ... a more nuanced approach is needed when prescribing antidepressants for pain [Giovanni Ferreira et al]

Using data from each review, the researchers estimated relative risks of pain or average differences in pain between groups on a 0-100 point scale, taking account of dose, treatment duration, and number of trials and participants.

They also assessed safety and tolerability (withdrawals due to adverse events), certainty of evidence, and risk of bias. Findings were then classified from each comparison as effective, not effective, or inconclusive. No review provided high certainty evidence on the effectiveness of antidepressants for pain for any condition. 

Nine reviews provided evidence that some antidepressants were effective compared with placebo for nine conditions in 11 distinct comparisons. For example, moderate certainty evidence suggested that serotonin-norepinephrine reuptake inhibitors (SNRIs) were effective for back pain (average 5.3 points lower on the pain scale than placebo), postoperative pain, fibromyalgia, and neuropathic pain.

SNRIs and knee osteoarthritis, among other conditions

Low certainty evidence suggested that SNRIs were effective for pain linked to breast cancer treatment, depression, knee osteoarthritis, and pain related to other underlying conditions. Low certainty evidence also suggested that selective serotonin reuptake inhibitors were effective for people with depression and pain related to other conditions; and that tricyclic antidepressants were effective for irritable bowel syndrome, neuropathic pain, and chronic tension-type headache. 

For the other 31 comparisons, antidepressants were either not effective (five comparisons) or the evidence was inconclusive (26 comparisons). Most safety and tolerability data were imprecise, indicating that the safety of antidepressants for several conditions is still uncertain.


This was a well-designed review based on a thorough literature search and the researchers took steps to minimise the impact of issues such as differences in study design and quality, imprecision and publication bias.

But the authors acknowledge that most comparisons had a limited number of trials, and results may not apply to antidepressants prescribed for symptoms linked to pain conditions, such as fatigue or sleep disturbance. Caution is also needed in interpreting these findings because almost half (45 per cent) of the trials forming the evidence for this review had ties to industry, they add.

In conclusion, they say: ‘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.’

To read the full version of the research paper, titled Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews doi: 10.1136/bmj-2022-072415 visit: https://www.bmj.com/content/380/bmj-2022-072415

To read the full version of the editorial, titled Rethinking use of medicines for chronic pain doi: 10.1136/bmj.p170, visit: https://www.bmj.com/content/380/bmj.p170

Author: Ian A McMillan
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