Can Antidepressants Help Chronic Pain?
Credit: Tatiana Ayazo

Key Takeaways 

  • Antidepressants are often prescribed for chronic pain, but there isn’t any high-quality evidence proving that these drugs work well for this purpose.
  • SNRIs like Cymbalta (duloxetine) are the most effective for certain types of chronic pain; there is less evidence to support the use of SSRIs and tricyclic antidepressants for pain.

If you live with chronic pain, which lasts for at least three months, it’s likely that you have tried various methods to alleviate it. While taking medication designed to treat underlying conditions such as rheumatic disease is crucial, it may not always be sufficient.

Many people experiment with different treatment modalities, such as physical therapy, supplements, and drugs like NSAIDs, acetaminophen, and opioids. Antidepressants are also commonly tried, even by those without depression, to address pain.

While conditions like rheumatoid arthritis often coincide with depression, antidepressants are often prescribed primarily for physical pain relief.

In fact, older adults in several countries, including the U.S. and Canada, are prescribed these drugs more often for chronic pain than for depression. These medications are typically used “off-label,” meaning doctors prescribe them for a purpose that hasn’t been officially approved. What’s surprising is that the evidence supporting the efficacy of antidepressants in relieving pain is rather limited.

What the Research Says

A recent study by a group of scientists from Australia and the UK delved into this issue by conducting an “overview of systematic reviews,” which is an analysis of previously conducted research reviews or meta-analyses. This process is designed to synthesize the highest level of currently available evidence on a topic. Their report was published in the BMJ.

To conduct this research, the group searched scientific databases and focused on 26 previously conducted research reviews. These 26 reviews contained 156 unique trials and a total of over 25,000 participants. None of the reviews yielded “high certainty evidence” that antidepressants were effective for pain caused by any condition.

However, this doesn’t necessarily mean that antidepressants are entirely useless for pain. The researchers found that there was “moderate certainty” evidence that antidepressants in the serotonin-norepinephrine reuptake inhibitor (SNRI) class are effective for four conditions:

The authors noted that, despite the “moderate certainty evidence” they uncovered, “it is unclear whether the effects are clinically relevant.” For example, in conditions where SNRIs were deemed efficacious with moderate certainty evidence (back pain, postoperative pain, and neuropathic pain), the reduction of pain compared with placebo was smaller than 10 points on a 0-100 scale.

SNRI antidepressants, including Cymbalta (duloxetine), Effexor XR (venlafaxine), Pristiq (desvenlafaxine), and Fetzima (levomilnacipran), are the ones studied. Cymbalta is the only one that’s officially FDA-approved to treat chronic pain.

Regarding selective serotonin reuptake inhibitors (SSRIs) such as Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline), the authors only found “low certainty evidence” that they were effective at treating chronic pain, and only in people who also suffer from depression.

According to the recent review, “low certainty evidence” suggests that tricyclic antidepressants (TCAs) may be effective in treating pain related to irritable bowel syndrome, neuropathic pain, and tension headaches.

TCAs are also the most commonly prescribed off-label antidepressant for pain. However, much of the evidence examined in the review was deemed “inconclusive,” including the use of SNRIs for sciatica pain, SSRIs for irritable bowel syndrome pain, and TCAs for back pain, bladder pain, fibromyalgia, rheumatoid arthritis, and sciatica.

The authors concluded that prescribing antidepressants for pain requires a more nuanced approach. Pain experts Cathy Stannard and Colin Wilkinson emphasized the importance of the review’s findings, noting that antidepressant treatment may not be effective for most adults with chronic pain. They also raised concerns about increasing antidepressant prescriptions and the challenges of withdrawing from these medications.

What You Should Know

Research has shown that there is no conclusive evidence to support the effectiveness of antidepressants in treating chronic pain. However, moderate evidence suggests that antidepressants in the SNRI class could be helpful in relieving back pain, postoperative pain, nerve pain, or fibromyalgia. It is important to discuss all medications, including antidepressants, with your doctor before starting or stopping them. They can provide advice and guidance on the best course of action based on your specific condition and medical history.

Be a More Proactive Patient with ArthritisPower

ArthritisPower is a patient-led, patient-centered research registry for joint, bone, and inflammatory skin conditions. You can participate in voluntary research studies about your health conditions and use the app to track your symptoms, disease activity, and medications — and share with your doctor. Learn more and sign up here.

Ferreira, G et al. “Efficacy, Safety, and Tolerability of Antidepressants for Pain in Adults: Overview of Systematic Reviews.” BMJ. February 1, 2023. doi: 

“Helpful for Chronic Pain in Addition to Depression.” Mayo Clinic. March 16, 2023. 

Stannard, C, et al. “Rethinking Use of Medicines for Chronic Pain.” BMJ. February 1, 2023. doi: 

Tamblyn R, et al. Multinational comparison of new antidepressant use in older adults: a cohort study. BMJ Open. doi: 

U.S. Food & Drug Administration. Understanding Unapproved Use of Approved Drugs “Off Label.” 2018. 

Wong, J et al. “Off-Label Indications for Antidepressants in Primary Care: Descriptive Study of Prescriptions from an Indication Based Electronic Prescribing System.” BMJ. February 21, 2017. 

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