Summary: Chronic pain and mood disorders like depression feed each other. So doctors often use antidepressants to manage chronic pain. But the largest study to date finds little proof that antidepressants help. Only one of these drugs has some proof behind it.
Doctors widely prescribe antidepressants for chronic pain. But a new review shows little proof that they help. It is one of the largest reviews to date. It pooled data from 176 trials. And it was published in one of the most trusted sources in medicine, the Cochrane Database of Systematic Reviews.
Chronic pain is one of the top causes of disability in the world, affecting one-third of the population. That means billions of people live with it.
But chronic pain is very different from acute (short-term) pain. Acute pain helps you survive. It lasts only as long as its cause, like a wound or injury that has not healed.
Chronic pain is a very different thing, and it is often poorly understood. It may start for no clear reason, or last long after the event that started it. It has many causes, such as mental and emotional factors, tissue or nerve damage, and even a nervous system that is too sensitive.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice for most pain. But they do not help enough with chronic pain. So doctors often prescribe other drugs, like opioids, anti-anxiety drugs, sedatives, anti-seizure drugs and antidepressants. These backup drugs do not always help. And often, doctors prescribe them just hoping they might.
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.
Chronic pain and mood disorders like depression feed each other. So using antidepressants to treat chronic pain is very common. Many doctors turn to these drugs when NSAIDs fail. But new studies question this approach. It may be doing more harm than good.
Do 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 rule out any benefit. So, what is the truth?
This study looked at the antidepressants most often prescribed for chronic pain in the UK. These drugs are also widely used in the US. The 25 antidepressants studied included 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. It was published in the Cochrane Database of Systematic Reviews in 2023. It included 176 randomized controlled trials with a total of 28,664 people. Most had fibromyalgia, neuropathic (nerve) pain, or musculoskeletal (muscle and joint) pain. The trials lasted 10 weeks on average.
Researchers found solid proof of benefit for only one drug, duloxetine, which worked moderately well. Milnacipran looked promising, but the proof was less certain. For every other antidepressant, the proof was low certainty.
So for some of the most popular antidepressants, like amitriptyline or sertraline, there is not enough solid proof to show whether they help chronic pain.
Also, the proof on side effects and safety was very low certainty for every antidepressant. So the review could not reach solid conclusions about their harms.
Even for duloxetine, the only antidepressant with solid proof of benefit, a high dose worked no better than the standard 60 mg dose for most results. So if a doctor prescribes it, it should be at its regular strength.
So the researchers concluded that duloxetine is the only antidepressant with solid proof for chronic pain. No antidepressant yet has solid proof of long-term benefit or safety for this use. They called for bigger, better trials, and for treatment guidelines to match the evidence. If you take an antidepressant for pain, review it with your prescriber. Do not stop it on your own.
Frequently asked questions
Which antidepressant is best for chronic pain?
Duloxetine is the only one with solid proof. The Cochrane review of 176 trials found it worked moderately well. Milnacipran looked promising, but the proof was less certain. Even with duloxetine, a high dose worked no better than the standard 60 mg dose for most results. So if it is prescribed, the regular strength is the one to use.
Does amitriptyline work for chronic pain?
There is not enough solid proof to say. Amitriptyline and sertraline are among the most popular antidepressants for pain. Yet the review rated the proof for them as low certainty. The same goes for every antidepressant except duloxetine and milnacipran. That means no one can show from the trials whether they ease chronic pain.
Why do doctors prescribe antidepressants for chronic pain?
Chronic pain and depression feed each other, so treating mood looks like a way to treat pain. Anti-inflammatory drugs such as NSAIDs often fail in chronic pain, and doctors want to help, so they reach for second-line drugs. Some guidelines even recommend them. The evidence has not kept up with the prescribing.
Are antidepressants safe for long-term pain treatment?
No antidepressant yet has solid proof of long-term benefit or safety for chronic pain. The trials lasted about 10 weeks on average. The proof on side effects was very low certainty for every drug studied. So the review could not reach firm conclusions about harms. The researchers called for bigger, better trials.
Should I stop taking my antidepressant for pain?
Not on your own. If you take an antidepressant for pain, review it with your prescriber rather than stopping it yourself. Ask whether it is actually helping your pain, and whether the evidence supports that drug and that dose. For most antidepressants, the trials cannot answer the first question with any certainty.
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
