No antidepressant found to be effective and safe for chronic pain, evidence review shows

The review of 176 studies included patients with a range of chronic pain conditions, including fibromyalgia, neuropathic pain and musculoskeletal pain.
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There is very little evidence supporting the long-term use of all antidepressants in patients with chronic pain, show results from an evidence review.

The Cochrane Collaboration metanalysis, published on 10 May 2023, considered 176 studies looking at a total of 25 different antidepressants and found “moderate to high-certainty” evidence for the effectiveness of the serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine.

Duloxetine standard dose (60mg) reduced substantial pain relief by 91% (95% confidence interval (CI) 1.69 to 2.17) and continuous pain intensity by a standardised mean difference of -0.31 (95% CI -0.39 to -0.24). Research showed there was “promising evidence for” the milnacipran, although the certainty of evidence was lower than that of duloxetine.

The studies included patients with a range of chronic pain conditions, including fibromyalgia, neuropathic pain and musculoskeletal pain, with the average length of the studies around ten weeks.

The researchers concluded: “The only antidepressant we are certain about for the treatment of chronic pain is duloxetine.”

However, they added: “There is currently no reliable evidence for the long‐term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.”

Emma Davies, advanced pharmacist practitioner in pain management at Cwm Taf Morgannwg University Health Board, said the review was helpful as it included a wider range of literature than is included in National Institute for Health and Care Excellence (NICE) guidance.

“Practically, I think we need to be cautious in how we respond. It is important that this isn’t used as a reason to remove these medicines from people without discussion or without due care,” she said.

“Whilst antidepressants may not be helpful for many people, they can also be problematic to reduce and stop and we need to get that balance right in order to avoid further harm.

“Conversely, for people who do find that antidepressants are helping them, perhaps by stabilising their mood, reducing pain perception and allowing improved function, then we should enable them to continue to take them for as long as those benefits are maintained.”

Cathy Stannard, clinical lead for the NICE guideline for chronic pain, said the review’s findings added to substantial evidence that the use of medicines to treat long-term pain is “disappointing”. 

“The conclusion that the best evidence is for the use of duloxetine is unsurprising,” she added. “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.”

Last updated
The Pharmaceutical Journal, PJ, May 2023, Vol 310, No 7973;310(7973)::DOI:10.1211/PJ.2023.1.184935

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