One in every five adults in the United States suffers from chronic pain. 1 Antidepressants have been prescribed off-label for decades to treat symptoms of conditions such as neuropathic pain, fibromyalgia, and migraine.
However, a new data review suggests that research on the antidepressants most commonly prescribed for pain is inconclusive.
Except for antidepressants, health authorities in the United Kingdom advised against using any medication for pain management in 2021. In response, a group of researchers compiled evidence from 26 review papers covering 156 trials and over 25,000 adult participants.
The researchers examined studies on how each of the eight antidepressant classes works to help patients manage 22 different pain conditions.
2 Almost a quarter of the antidepressant-condition combinations showed some efficacy. However, antidepressants appeared ineffective for pain management in the other 31 cases, or the evidence was inconclusive.
The most commonly prescribed class of antidepressants for pain is tricyclic acids (TCAs). However, the review concluded that there is “low certainty” that these drugs effectively treat any pain condition. SNRIs, on the other hand, appeared to be beneficial for people suffering from seven types of pain.
What You Should Know About SSRIs vs. SNRIs
According to Giovanni Ferreira, PhD, a fellow in the Institute for Musculoskeletal Health at the University of Sydney School of Public Health and the study’s lead author, providing these drugs without sufficient evidence that they are effective at relieving pain could cause patients to experience unpleasant side effects.
“A person is more than just a painful condition.” “The decision to use or not use those drugs must take into account not only the pain problem, but also the individual’s broader context,” Ferreira told Verywell. “Hopefully, our review will be able to inform some of these situations where prescriptions may or may not be appropriate.”
How Are Antidepressants Used to Treat Pain?
There are no one-size-fits-all pain medications, and many have negative side effects or are ineffective. Acetaminophen, for example, is the most commonly used non-opioid pain reliever, but it’s unclear how effective it is in treating acute lower back pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), another common pain reliever, should only be used for short periods of time.
Some clinicians may use antidepressants instead of opioids, which can be highly addictive.
According to Jamal Hasoon, MD, an assistant professor and director of the pain fellowship program at UTHealth Houston, antidepressants are not a first-line treatment for pain. He stated that he usually begins with Neurontin (gabapentin) or Lyrica (pregabalin) before moving on to antidepressants or other treatments.
Hasoon, who is not affiliated with the study, believes that patients with neuropathic pain benefit the most from antidepressants, whereas those with more “mechanical” pain, such as arthritis, may not benefit as much.
Scientists do not yet understand how antidepressants work to reduce pain. According to one popular theory, they increase the levels of certain neurotransmitters, which reduce pain signals.
“Chronic pain is such a complicated situation that even with our best scientific understanding of mechanism of action… there’s so much at play that I think we’ve got a decent understanding but I don’t think we’ve got it completely figured out,” Hasoon told Verywell.
According to Hasoon, there is a stigma associated with pain management doctors prescribing antidepressants. It’s critical that patients understand that when doctors prescribe antidepressants for pain, they’re not diagnosing a psychiatric disorder. Nonetheless, while most antidepressant dosages for pain management are too low to fully treat depressive symptoms, some overlapping effects may occur.
“If you have chronic pain and are in pain 24 hours a day, seven days a week, you will be depressed.” “There’s so much comorbid depression and anxiety that you’re co-managing,” Hasoon explained.
SNRIs Could Be the Most Effective Painkillers
According to the review, SNRIs appear to be more effective than any other class of antidepressants in treating a wider range of conditions. These drugs are involved in four of the 11 drug-condition comparisons for which there is moderate certainty of evidence.
The only FDA-approved antidepressant for neuropathic pain is the SNRI duloxetine. It is approved for the treatment of fibromyalgia, chronic musculoskeletal pain, and diabetic peripheral neuropathic pain.
The review concluded that there is moderate certainty of evidence that SNRIs can relieve back pain, postoperative pain, fibromyalgia, and neuropathic pain. Meanwhile, evidence for knee osteoarthritis, depression with comorbid chronic pain, and pain caused by aromatase inhibitors is uncertain (which are sometimes used to treat breast cancer).
However, Ferreira cautioned that many of the studies on SNRI efficacy were funded by industry. “These trials tend to produce more optimistic results than, say, trials conducted by independent investigators,” he said.
Many of the studies included in the review used different methods to assess how well drugs worked. The researchers indicated efficacy if the antidepressant, for example, was significantly better than a placebo at reducing pain.
“We wanted to leave it up to the patient and clinician to decide whether that effect is large enough,” Ferreira said.
TCA Benefits for Pain Reconsidered
According to a Quebec review, approximately three-quarters of antidepressant prescriptions for a pain condition involved a TCA.
6 According to Hasoon, this class accounts for at least half of the antidepressants prescribed for pain in the United States.
However, the studies supporting the use of TCAs for pain are older and smaller than those supporting the use of SNRIs.
“The SNRI pathway has provided the majority of the benefits, but tricyclics are simply more commonly prescribed,” Hasoon explained. “My assumption is that tricyclics are older drugs, are less expensive, and are probably easier to get insurance to approve.”
The review provided efficacy estimates for the use of TCAs to treat pain in 14 different conditions. They discovered that the drugs were effective for only three conditions: irritable bowel syndrome (IBS), neuropathic pain, and chronic tension-type headache, but the evidence for those conditions was mixed.
This antidepressant class does not appear to be effective for chronic indigestion, back pain, bladder pain syndrome, fibromyalgia, rheumatoid arthritis, or sciatica.
“As a patient, I would prefer not to receive a treatment for which the evidence is inconclusive,” Ferreira explained. “If there is uncertainty and other options for pain management exist—which there are—I believe it is reasonable to wait until we know more about the efficacy of specific treatments.”
SSRIs Do Not Seem to Be Effective for Pain Management
SSRIs, such as Prozac (fluoxetine) and Zoloft (sertraline), work by increasing serotonin levels in the brain.
“Most studies have shown that SSRIs only work on the serotonin pathway—people don’t usually get much of a response from that.” They may alleviate their depression symptoms, but they do not alleviate their pain symptoms,” Hasoon explained.
According to the review, there is a low certainty of evidence that SSRIs can help with depression and comorbid chronic pain, but no evidence that they can help with other pain conditions.
There is no evidence to support their use for back pain, fibromyalgia, functional dyspepsia (chronic indigestion), non-cardiac chest pain, or IBS.
Erin Balsa is a highly skilled and knowledgeable health journalist with a passion for educating the public on important health and wellness topics. With extensive experience in both traditional and digital media, Erin has established herself as a trusted voice in the field.