Antidepressants mostly can’t treat chronic pain, despite wide use

Ongoing pain, such as chronic back or neck pain, is difficult to treat, so some doctors prescribe antidepressants. Now, a review of evidence says these drugs mostly don’t work as a treatment

By Clare Wilson

People in long-term pain are often offered antidepressants when other treatments have failed, but a review of clinical trials has found little evidence to support using most such drugs in this way.

It is estimated that about 1 in 5 people have ongoing pain, with a variety of causes, including arthritis or nerve damage, and locations, including in the back or neck.

But treatment options are limited. While opioid-based medicines are effective for new-onset pain, they can be addictive when used long term. Other drugs, such as pregabalin, can also cause addiction, while anti-inflammatory drugs can treat pain, but may cause damage to the stomach, kidneys and heart with extended use.

This may be why some doctors offer antidepressants as treatment for long-term pain – even though they generally aren’t licensed for such use and must be prescribed “off-label”.

Some people with chronic pain are also depressed or anxious, so doctors could see the medicines as primarily helping these conditions, but antidepressants are also thought to have a separate painkilling effect. The mechanism is unknown, but one idea is that it stems from antidepressants dampening inflammation, at least in animal tests.

It is hard to quantify the use of antidepressants for pain, as official figures for drugs generally don’t record the medical condition they were prescribed for, meaning treatment for pain is lumped in with those for depression and anxiety.

But various studies give an indication. For example, one paper suggests that 1 in 10 antidepressant prescriptions in Canada were for pain, while recent figures from the UK and US suggest that among people over 65, chronic pain was the most common reason for taking an antidepressant. “They have been used for pain for quite some time,” says Giovanni Ferreira at the University of Sydney.

Ferreira and his colleagues have now conducted a detailed breakdown of the supporting evidence, analysing the results of 156 randomised trials involving more than 25,000 participants. They looked at the effectiveness of eight types of antidepressant at treating 22 pain conditions, such as back pain, postoperative pain and fibromyalgia, where people have widespread muscular pain.

The team found there was no good evidence for the effectiveness of most of the drugs, including a class called tricyclic antidepressants, which are the most common type used for treating pain in the UK, and the selective serotonin reuptake inhibitors (SSRIs), which are the most common type used in the US.

The one class that did have evidence of effectiveness was a kind called serotonin and norepinephrine reuptake inhibitors, or SNRIs. But even these reduced pain by a modest amount: less than 10 points on a scale of 0 to 100. “It seems to be a small difference,” says Ferreira. Asking people to subjectively rate their pain on a numerical scale is the only way to gauge its extent, which makes diagnosis and treatment of pain all the harder.

The analysis comes to different conclusions than a 2021 review by the National Institute for Health and Care Excellence (NICE), the medical guidelines body for England and Wales, which said antidepressants were the only class of medicines that doctors should consider for chronic pain, although this should only be after discussing the potential benefits and harms. The difference in conclusions may be because the latest analysis included more trials and considered each pain condition separately, says Ferreira.

Cathy Stannard at NHS Gloucestershire Integrated Care Board in Gloucester, UK, who advised on the NICE guidelines, says the new review doesn’t mean doctors should rule out antidepressants. “Some people will get a useful benefit and there’s no way of predicting who that will be,” she says.

But there is unlikely to be any pharmacological “magic bullet” for chronic pain, says Stannard. Doctors and people in pain should consider exploring other options, such as specialist group exercise classes or trying to tackle other difficulties in their life, like job stress or social isolation, which can amplify the impact of long-term painful conditions, she says.

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