Key messages

• Compared with a placebo (inactive or 'dummy' pill), serotonin and norepinephrine reuptake inhibitors (a class of antidepressant) probably provide small reductions in pain intensity and trivial improvements in function in people with low back pain. Some people will probably experience unwanted effects when taking these medicines.

• Compared with a dummy pill, tricyclic antidepressants (a class of antidepressant) probably provide small improvements in function in people with low back pain, but probably have little to no effect on pain intensity.

• We are uncertain about the effects of any antidepressant for the treatment of spine-related leg pain.

What are low back pain and spine-related leg pain?

Low back pain is a leading cause of disability around the world. Most cases of low back pain are called 'non-specific' because they are not caused by clear damage to the spine. Many people with low back pain also experience pain that radiates into the leg.

How do antidepressants treat low back pain and spine-related leg pain?

Antidepressants are a group of medicines that were originally developed to treat depression. The most common classes are serotonin and norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants. Antidepressants are thought to relieve pain by blocking pain signals in the nervous system. Some people who take antidepressants might experience unwanted effects, such as dry mouth and nausea.

What did we want to find out?

We wanted to find out if antidepressants are more effective than a dummy pill, standard care, or no treatment, at relieving pain and increasing function in people with low back pain or spine-related leg pain. We also looked at whether antidepressants were associated with unwanted effects.

What did we do?

We searched for studies that compared antidepressants with a dummy pill, standard care, or no treatment, in people with low back pain or spine-related leg pain. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?
This is an update of a Cochrane review first published in 2008. We found 26 studies involving 2932 people: 18 studies included 2535 people with low back pain; seven studies included 329 people with spine-related leg pain, and one study included 68 people with either condition. The average age of participants ranged from 27 to 59 years. Participants had 'chronic' symptoms (lasting more than 3 months) in 62% of studies. The study periods lasted from 1 day to 6 months. Studies investigated serotonin and norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, tetracyclic antidepressants, or other types of antidepressants (grouped as 'other antidepressants'), all compared with a dummy pill. The studies were conducted around the world, but most were in high-income countries, including the USA, United Kingdom, France, Japan, and Australia. Almost half the included studies were funded by pharmaceutical companies.

Main results

We found that serotonin and norepinephrine reuptake inhibitors probably provide small reductions in pain intensity and trivial improvements in function in people with low back pain.

We also found that tricyclic antidepressants probably provide small improvements in function, but are unlikely to reduce pain intensity, in people with low back pain.

We do not know if selective serotonin reuptake inhibitors, tetracyclic antidepressants, or other antidepressants reduce pain intensity and improve function in people with low back pain.

For people with spine-related leg pain, we do not know if any antidepressant reduces pain and increases function.

Serotonin and norepinephrine reuptake inhibitors probably increase the risk of experiencing unwanted effects. It is unclear whether the other antidepressant classes increase the risk of unwanted effects and serious unwanted events.

What are the limitations of the evidence?

Our confidence in the evidence for serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants is only moderate because not all studies provided data about everything we were interested in.

We have little or no confidence in the rest of the evidence in this review because not all studies provided data about everything we were interested in, the studies were very small, and there were not enough studies to be certain about the results of our outcomes of interest.

The results of further research could differ from the results of this review.

How current is this evidence?

This review updates our previous review. The evidence is current to November 2024.