May 10, 2023

expert reaction to Cochrane review on antidepressants for pain management in adults with chronic pain

A meta-analysis published by Cochrane looks at the use of antidepressants for pain management in adults with chronic pain.

This Roundup accompanied an SMC Briefing.

Dr Ryan Patel, Prof Anthony Mellows/King’s Prize Fellow, King’s College London, said:

“If you are someone living with chronic pain and taking antidepressant drugs to manage your symptoms, the best advice is to continue taking them if they work for you.

“The systems that regulate mood and pain overlap considerably meaning some antidepressants can provide pain relief. 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. 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. In most areas of medicine the aim is to match the treatment selection to the underlying biology. The question that should be asked is not ‘are antidepressant drugs effective for treating pain?’ but ‘for whom are antidepressants effective?’ 

“As the authors of this study emphasise not all antidepressants work in the same way, and therefore not all drugs will have a common biological target in pain and depression. To avoid unnecessary stigmatisation, it makes much more sense to define drugs by what they do rather than what they treat. It is telling that the most effective drugs for pain relief (duloxetine and milnacipran) are dual serotonin and noradrenaline reuptake inhibitors, but even within the same class of drugs there will be differences in how effective they are. Some drugs may have greater actions on serotonin than noradrenaline and vice versa; each individual drug needs to be evaluated separately.

“Hopefully this study will be the driver for better designed clinical trials where the emphasis is placed on identifying predictive factors for therapeutic response so that treatment selection can be personalised.”

Dr Lorraine de Gray, Dean of the Faculty of Pain Medicine, Royal College of Anaesthetists, said:

“The Faculty of Pain Medicine welcomes the publication of this Cochrane review which will help guide the pharmacological management of people suffering from chronic pain.

“We would like to point out that the proposed statement is erroneous in its statement: “Amitriptyline is one of the most commonly prescribed antidepressants for pain management worldwide. In the last 12 months, around ten million prescriptions were given to patients in England at the 10mg dose recommended for pain. By comparison, five million prescriptions were given at the higher doses recommended for depression”.

“The paper does not state that 10mg is the dose recommended for chronic pain. Indeed on Page 243, table one states that the standard dosage used is 25 to 75mg.  This is reflected in the British National Formulary which for Amitriptyline states: Initially 10–25 mg daily, dose to be taken in the evening, then increased, if tolerated, in steps of 10–25 mg every 3–7 days in 1–2 divided doses; usual dose 25–75 mg daily, dose to be taken in the evening, doses above 100 mg should be used with caution (doses above 75 mg should be used with caution in the elderly and in patients with cardiovascular disease); maximum per dose 75 mg.

“Additionally, although not explicitly recognised in the paper, one of the major problems with the research base is the lack of good quality trials for older medications, primarily an issue of these medications being long out of patent and unable to attract the funding needed for such trials. This does not exempt them from study, but requires research frameworks, and regulatory authorities, to recognise the need not just to assess efficacy against placebo, but also against assumed (and often cheaper) treatments.”

Dr Cathy Stannard, Clinical Lead, NICE Guideline for Chronic Pain, and Clinical Lead, Pain Transformation Programme, NHS Gloucestershire Integrated Care Board, said:

“This well conducted review adds to the substantial evidence we now have that shows that the use of medicines to treat long term pain is disappointing.  In contrast to the NICE Guideline on Chronic Pain 2021 this review examines the role of antidepressants for a diverse group of chronic pain diagnoses. The conclusion that the best evidence is for the use of duloxetine is unsurprising.   Trials (many industry sponsored) for this newer drug were necessarily more rigorously conducted, given the contemporary regulatory environment and understanding of clinical evidence, than were those for older medicines such as amitriptyline. The difficulty in using results from the very circumscribed setting of a clinical trial to the real-life use of medicines in unselected populations, often for months or years is an important emphasis of the review. 

“The study rightly highlights the significant adverse effect that chronic pain has on the quality of life for the people living with it. It’s equally important to emphasise the many social and psychological influences on the pain experience. Existing services, usually outside healthcare, including support with mobility, debt management, trauma, and social isolation, can be helpful for people living with pain and identifying what matters most to people and signposting to appropriate local support is a promising way forward. 

“There is good evidence that for people with pain, compassionate and consistent relationships with clinicians remain the foundations of successful care. 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.”

‘Antidepressants for pain management in adults with chronic pain: a network meta-analysis’ by Tamar Pincus et al. was published by Cochrane at 00:01 UK time on Wednesday 10 May 2023.

DOI: 10.1002 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014682.pub2/full

Declared interests

Dr Ryan Patel: “I have no conflicts of interest to declare.”

Dr Lorraine de Gray is a co-opted member of the Council of the Royal College of Anaesthetists, representing the Faculty of Pain Medicine. She is Consultant in Anaesthesia and Pain Management at the Queen Elizabeth Hospital NHS Foundation Trust, Norfolk, President of the Anglian Pain Society and Specialty Editor for Pain Medicine, Journal of Anaesthesia and Intensive Care (Elsevier).

Dr Cathy Stannard: “My COIs are that I was clinical lead for the NICE guideline on chronic pain and topic advisor for the NICE guideline in safe prescribing of medicines associated with addiction and withdrawal. No other COIs.”