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Antidepressants do not help with chronic pain in the long run, a new review has concluded. Image credit: Mickey Cashew/Getty Images.
  • In a new review and meta-analysis, researchers investigated whether antidepressants can treat chronic pain conditions.
  • They found that antidepressants are largely ineffective in treating chronic pain.
  • Further research is needed to understand how antidepressants may be used to treat chronic pain.

Chronic pain is defined as pain lasting or recurring for 3 months or longer. In 2021, around 51.6 million adults in the United States — or 20.9% of the adult population — experienced chronic pain.

Depression and pain conditions share several neural pathways. Estimates suggest that 35–45% of people with chronic pain experience depression.

Earlier this year, a meta-analysis of 26 studies found that antidepressants were effective in relieving pain in around 25% of cases. However, for the remaining 75% of cases, antidepressants were either inefficacious or data was inconclusive.

Understanding more about the potential of antidepressants for treating chronic pain could improve treatment options for the condition.

More recently, a Cochrane review published in the Cochrane Database of Systematic Reviews also assessed the efficacy of antidepressants in treating adults with chronic pain.

The review found that antidepressants are ineffective for long-term pain relief but that one drug — duloxetine — could provide short-term relief.

For the review, the researchers analyzed data from 176 studies including 28,664 participants who had fibromyalgia, neuropathic pain, or musculoskeletal pain.

In each of the studies included, patients were treated with an antidepressant or a comparator such

  • a placebo
  • another medication
  • another antidepressant
  • the same antidepressant at different doses
  • psychotherapy.

Altogether, the researchers studied 25 different antidepressants, including:

The interventions lasted for an average of 10 weeks, and 72 of the studies were fully funded by pharmaceutical companies, while 32 did not report the source of their funding.

In the end, the researchers found no evidence that antidepressants can induce long-term pain relief for chronic pain conditions.

They did find, however, that duloxetine may have a moderate effect on short-term pain relief. Of every 1,000 people taking the drug, 435 experienced 50% pain relief compared to 287 experiencing 50% pain relief on a placebo.

The researchers noted that gaps in current evidence mean that the effects of long-term duloxetine use remain unknown.

They also found that milnacipran may also reduce pain. However, they noted that further research is needed due to the few studies that reviewed this drug.

To understand why duloxetine and milnacipran — and not other antidepressants — may reduce chronic pain in the short term, Medical News Today spoke with Dr. Alex Dimitriu, double board-certified in psychiatry and sleep medicine, and founder of Menlo Park Psychiatry & Sleep Medicine, not involved in the study.

He told us: “Both duloxetine and milnacipran offer some advantage to pain. The reason is that these medications work on norepinephrine, implicated in pain perception, as well as serotonin, implicated in depression.”

MNT also spoke with Dr. Akshay Goyal, double board-certified pain management physician at Baptist Health Miami Neuroscience Institute, not involved in the study.

He also noted that both duloxetine and milnacipran are serotonin and norepinephrine uptake inhibitors (SNRIs), meaning the medications prevent the breakdown of these neurotransmitters. He indicated that higher levels of both norepinephrine and serotonin are responsible for improvements in pain perception.

When asked about the study’s limitations, Dr. Lokesh Shahani, associate professor of psychiatry at UTHealth Houston, not involved in the study, told MNT: “The majority of the included studies were limited to an average [of] 10 weeks of follow-up. Hence data on long-term efficacy and safety on use of antidepressants for chronic pain is lacking.”

Dr. Goyal added that another major limitation of the study is that it excluded individuals diagnosed with anxiety or depression, even though many chronic pain patients have one or both of these conditions:

“The biopsychosocial treatment approach dictates that as chronic pain physicians, we must use a multimodal approach to target not only patients’ musculoskeletal pain, but also optimize their surrounding psychosocial issues. Patients with untreated anxiety or depression often have an exaggerated pain response to minor noxious stimuli. Excluding these patients from the analysis removes a valuable subset of patients that we treat.”

“Another limitation of the study is the fact that most of the data reviewed was for duloxetine and milnacipran — both of which are SNRIs — due to lack of available evidence for other medications,” he explained.

MNT also asked Dr. Goyal about key takeaways from the study. He noted that the findings must be interpreted very carefully in the appropriate clinical context.

“Antidepressants such as duloxetine and amitriptyline are a valuable tool when treating chronic pain conditions, especially difficult-to-treat conditions such as neuropathic pain and fibromyalgia,“ he pointed out.

“In my clinical experience, when patients fail treatment with other anti-neuropathic agents such as gabapentin or pregabalin, antidepressants have been useful adjuncts for not only decreasing pain intensity but also improving functionality,” he explained.

“This study reinforces my practice of using duloxetine at low to moderate doses for my patient population,” Dr. Goyal concluded.