Most depression drug prescribed for chronic pain may be not effective or safe

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Scientists have warned that most antidepressants used for chronic pain are being prescribed with “insufficient” evidence of their effectiveness.

A major investigation into medications used to manage long-term pain has found that many of the commonly recommended drugs have not been well studied, and the harms of some of these drugs have not been fully researched.

What the study found

The study, published in the Cochrane Database of Systematic Reviews, examined 176 trials consisting of nearly 30,000 patients involved in assessments that prescribed antidepressants for chronic pain.

Among the drugs studied were amitriptyline, fluoxetine, citalopram, paroxetine, sertraline, and duloxetine—with only the latter showing reliable evidence for pain relief.

One third of people globally are living with chronic pain, according to World Health Organization data, with many prescribed antidepressants for relieving symptoms.

Concerns over safety and long-term effectiveness

Lead author Professor Tamar Pincus from the University of Southampton said that the lack of scientific proof of the long-term efficacy of any antidepressant and their safety for chronic pain is a global public health concern.

The study found no reliable evidence for the long-term efficacy of any antidepressant or its safety for chronic pain at any point.

Though the study did find that duloxetine provided short-term pain relief for patients, the researchers remain concerned about its possible long-term harm due to the gaps in current evidence.

Amitriptyline is one of the most commonly prescribed antidepressants for pain management worldwide.

In the last 12 months, around ten million prescriptions were given to patients in England at the 10mg dose recommended for pain.

By comparison, five million prescriptions were given at the higher doses recommended for depression.

Call for updates in treatment guidelines

The two-year Cochrane study was the largest-ever assessment of antidepressants recommended by leading bodies including the UK’s National Institute for Health and Care Excellence (NICE) and the Food and Drug Administration (FDA) in the U.S.

Statistician Gavin Stewart, review co-author from Newcastle University, said, “We are calling on governing health bodies NICE and the FDA to update their guidelines to reflect the new scientific evidence, and on funders to stop supporting small and flawed trials.

Evidence synthesis is often complex and nuanced, but the evidence underpinning the use of these treatments is not equivalent, so current treatment modalities are hard to justify.”

Recommendations for treatment

The review revealed that duloxetine was consistently the highest-rated medication and was equally effective for fibromyalgia, musculoskeletal, and neuropathic pain conditions.

Standard doses of duloxetine are as successful for reducing pain as higher quantities.

Milnacipran was also effective at reducing pain, but scientists are not as confident as duloxetine due to fewer studies with fewer people.

However, it is important to note that there is not enough evidence for other antidepressants because there were not enough high-quality studies to determine their effectiveness for chronic pain.

Prof. Tamar Pincus added, “We simply cannot tell about other antidepressants because sufficiently good studies are not available—but it does not mean that people should stop taking prescribed medication without consulting their GP.”

The researchers suggested that patients and clinicians should take a person-centered approach to treatment, and when patients and clinicians decide together to try antidepressants, they should start from the drug for which there is good evidence.


The lack of sufficient scientific evidence on the long-term efficacy of antidepressants and their safety for chronic pain is a cause for concern.

The researchers have called for governing health bodies NICE and the FDA to update their guidelines to reflect new scientific evidence, and on funders to stop supporting small and flawed trials.

If you care about pain, please read studies that 1 in 3 people with chronic pain turn to marijuana, and powerlifting is an effective exercise for chronic low back pain.

For more information about wellness, please see recent studies that Krill oil could improve muscle health in older people, and eating yogurt linked to lower frailty in older people.

The study was published in the Cochrane Database of Systematic Reviews.

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