Summary: Chronic pain has a bidirectional relationship to mood disorders like depression. Thus, doctors frequently use antidepressants to manage chronic pain. However, the most extensive study to date shows that there is little evidence that antidepressants help. There is only some evidence in favor of one of these drugs.
Antidepressants are widely prescribed to manage chronic pain. However, a new review, one of the most extensive to date, analyzing data from 176 trials and published in one of the most reputable sources of medical evidence, the Cochrane Database of Systematic Reviews, shows little evidence that antidepressants help.
Chronic pain is one of the most common causes of disability globally, affecting one-third of the population, which means that billions are affected by chronic pain globally.
However, chronic pain is very different from acute pain. Acute pain is a survival mechanism; such pain lasts only as long as the underlying cause, like unhealed physical trauma or a wound.
In contrast, chronic pain is a very different and often poorly understood phenomenon. Such pain may start for no apparent reason or outlast the event that initiated the pain. It occurs for many reasons, such as psychological, tissue, nerve damage, and even hypersensitivity of the nervous system.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the treatment of choice for most pains. However, they fail to help adequately in chronic pain. Thus, doctors often prescribe other drugs, like opioids, anti-anxiety drugs, sedatives, anti-seizure, and antidepressants. However, the prescription of these second-line drugs does not essentially help. Moreover, in many cases, doctors prescribe them off-label, believing that they might help.
Of course, doctors have a reason to prescribe these drugs. They want to help patients. Some treatment guidelines might even recommend them. However, these second-line drugs are highly toxic and rarely help. They might cause more side effects than good.
Since chronic pain has a bidirectional relationship with mood disorders like depression, the use of antidepressants as a part of chronic pain treatment is very common. Many doctors would opt for these drugs if NSAIDs fail to help. However, new studies have questioned this approach. Such an approach might be causing more harm than good.
Little Evidence that Antidepressants Help with Chronic Pain
This new study is the largest investigation to date. The purpose of the study was to understand if antidepressants help or not. There are some studies claiming that they might be of some help, while others ruling out any benefit. So, what is the truth?
This study looked into the most commonly prescribed antidepressants for chronic pain in the UK. These antidepressants are also commonly used in the US, too. Among the 25 antidepressants studied were amitriptyline, duloxetine, fluoxetine, citalopram, paroxetine, and sertraline.
This was a systematic review with network meta-analysis – a kind of study that pools data from other studies. Published in the Cochrane Database of Systematic Reviews in 2023, it included 176 randomized controlled trials with a total of 28,664 participants, most often with fibromyalgia, neuropathic pain, or musculoskeletal pain. The trials lasted 10 weeks on average.
Researchers found reliable evidence of benefit for only one of the drugs, duloxetine, which was moderately effective. Milnacipran showed promising results, although the evidence was less certain. For every other antidepressant, the evidence was of low certainty.
This means that for some of the most popular antidepressants, like amitriptyline or sertraline, there is not enough reliable evidence to show whether they help with chronic pain.
Further, the evidence on side effects and safety was of very low certainty for every antidepressant, so the review could not draw reliable conclusions about their harms.
Even in the case of duloxetine, the only antidepressant with reliable evidence of benefit, a high dose worked no better than the standard 60 mg dose for most outcomes. Thus, if this specific drug is prescribed, it should be prescribed in its regular strength.
Hence, the researchers concluded that duloxetine is the only antidepressant with reliable evidence for chronic pain, and that no antidepressant yet has reliable evidence of long-term benefit or safety for this use. They called for larger, better-designed trials and for treatment guidelines to reflect the evidence. Anyone taking an antidepressant for pain should review it with their prescriber rather than stopping it on their own.
Source:
Birkinshaw, H., Friedrich, C. M., Cole, P., Eccleston, C., Serfaty, M., Stewart, G., White, S., Moore, R. A., Phillippo, D., & Pincus, T. (2023). Antidepressants for pain management in adults with chronic pain: a network meta-analysis. Cochrane Database of Systematic Reviews, 5(5), CD014682. https://doi.org/10.1002/14651858.CD014682.pub2
Most antidepressants prescribed for chronic pain lack reliable evidence of efficacy or safety, scientists warn. (n.d.). Retrieved May 27, 2024, from https://www.cochrane.org/news/most-antidepressants-prescribed-chronic-pain-lack-reliable-evidence-efficacy-or-safety
Dr. Gurpreet Singh Padda, MD, MBA, MHP
