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Did you know that antidepressant medications are often prescribed for people without depression?

It’s true. Antidepressants are frequently prescribed for chronic pain, especially pain related to nerve disease (called neuropathic pain), chronic low back or neck pain, and certain types of arthritis.

In fact, some guidelines for the treatment of chronic low back pain and osteoarthritis (the most common type of arthritis) include antidepressants. One antidepressant in particular, duloxetine (Cymbalta), is FDA-approved for these conditions.

Just how antidepressants reduce pain is not well understood. One possibility is they affect chemicals in the brain involved in pain perception, a mechanism that differs from how they fight depression.

But a recent study calls into doubt how much pain relief antidepressants really deliver.

For people with chronic low back or neck pain or osteoarthritis of the hip or knee, an antidepressant medication is not usually the first treatment recommended. Other approaches, such as physical therapy, exercise, losing excess weight, nonsteroidal anti-inflammatory drugs (NSAIDs), or cortisone injections are usually tried first.

But if these aren’t helpful, antidepressants such as duloxetine or amitriptyline might be a reasonable next step.

When prescribed for pain, the initial dose is typically low (often lower than the starting dose for depression). It’s gradually increased if necessary.

Ideally, people notice a benefit within weeks of starting the drug, and the medication can be continued at the lowest effective dose.

Switching to a different antidepressant may be recommended if pain is not well controlled, side effects develop, or there is an interaction with another medication.

Research suggests minimal benefit

Past research on antidepressants for chronic pain, such as duloxetine for osteoarthritis of the knee, amitriptyline or duloxetine for chronic low back pain, and amitriptyline for chronic neck pain, demonstrated modest, short-term benefit.

But the studies were limited. Most trials were small and lasted only a few months or less. Notably, medication side effects — such as nausea, constipation and erectile dysfunction — were common in these trials.

Now, a 2021 study has combined the data from past research to get a better sense of just how safe and effective antidepressants are for these conditions. The news isn’t good:

On average, treatment with antidepressants minimally reduced pain and disability compared with placebo. The improvement in pain — about 4 points on a scale of 0 to 100 — was considered too small to be noticeable.

People treated with certain antidepressants for chronic pain often stopped taking the medication because it didn’t work, caused unacceptable side effects, or both.

People with both chronic pain and depression did not experience more improvement than people with chronic pain alone.

Sciatica may be an exception: antidepressants may have reduced pain for up to a year. However, the quality of the prior research was poor, so the study authors were not confident about these conclusions.

These findings cast doubt on the usefulness of antidepressant treatment for these common causes of chronic pain. However, they don’t rule out the possibility that some individuals may get more relief from these medications than others.

The bottom line

The available evidence suggests that, on average, the benefit of antidepressants for osteoarthritis or chronic low back pain and neck pain is modest at best, and tends to be temporary.

That’s disappointing because, for many pain sufferers, there are no reliably effective treatments (short of joint replacement for osteoarthritis).

So, if you’re on an antidepressant for pain and you aren’t sure if it’s working, talk to your doctor about whether you should consider stopping it.

Not only might you simplify your medical regimen, you may also reduce the cost of your medicines and the risk of medication-related side effects.

But don’t stop it on your own. There may be other reasons your doctor is recommending this medication, and many antidepressants should be gradually reduced, not stopped all at once, to avoid discontinuation symptoms.

Robert H. Shmerling, M.D., is a senior faculty editor at Harvard Health Publishing.

© Harvard University. Distributed by Tribune Content Agency, LLC.