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Antidepressants: pain, no gain

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Antidepressants are the only drug that doctors are advised to prescribe for chronic pain—but a new study has discovered they don’t work

Getting something for our aches and pains is one of the most common reasons we visit the doctor. But instead of leaving with a prescription for a painkiller, we’re just as likely to be given an antidepressant.

Doctors have been using antidepressants as pain relievers since the 1960s, but the practice has exploded in recent years with the opioid scandal, which has resulted in whole towns in the US addicted to the analgesics.

Today, antidepressants are the only drugs that doctors should be prescribing for chronic pain, according to best-practice guidelines drawn up by the UK’s NICE (National Institute for Health and Care Excellence), which determines how doctors treat. Standard painkillers, such as the NSAIDs (non-steroidal anti-inflammatory drugs), paracetamol or acetaminophen, and benzodiazepines, shouldn’t be prescribed because there’s no evidence they work.

Even then, antidepressants such as amitriptyline, citalopram, fluoxetine and sertraline don’t reduce the pain, but they help the patient cope with the life-destroying consequences of chronic pain, such as insomnia and psychological distress, the NICE has determined.

Doctors don’t entirely agree. Yes, antidepressants can ease psychological issues with chronic pain, but the tricyclic antidepressants (TCAs)—and, more recently, the tetracyclic antidepressants (TeCAs)—work on the same chemical pathways that influence pain, which suggests they could have pain-relieving qualities.

The drugs don’t work

But even this last stool has just been kicked from under the doctor. An independent analysis agrees with the NICE that antidepressants don’t relieve pain, which suggests that any positive effect is imagined by the patient; in other words, they are a placebo.

A research team from the Cochrane Collaboration took another look at 176 studies that had measured the effectiveness of 25 different antidepressants on a total of nearly 30,000 chronic pain sufferers who had fibromyalgia, neuropathic pain or musculoskeletal pain, such as from arthritis. A successful drug was one that could at least halve pain levels, the researchers determined.1

All the drugs they reviewed were being prescribed purely as pain relievers, and not because the patient was also suffering from depression.

But none of the drugs—bar one—came up to scratch. Duloxetine, an SNRI (serotonin-noradrenaline reuptake inhibitor) antidepressant, was the only one that came even close, achieving “mild to moderate” pain relief. Ironically, duloxetine, marketed as Cymbalta, is so expensive that doctors rarely prescribe it. In the US, duloxetine is the only antidepressant that has been approved by the FDA (Food and Drug Administration) for use as a painkiller.

Risks and rewards

The risks may not be worth the slight reward, however. Around 1 percent of antidepressant users suffer hallucinations, constant headache and stomach bleeds and cough up blood, although none of the studies the Cochrane researchers looked at had followed the patients long enough to witness any serious side effects.

There was no evidence that the most frequently prescribed antidepressant—amitriptyline, a tricyclic marketed as Elavil—had any positive effect on pain relief at all. But it’s the cheapest antidepressant on the market, and so was probably selected for that reason rather than for its potential pain-relieving qualities. In just one year in England, 15 million doses of amitriptyline were prescribed to treat pain.

The Cochrane reviewers have some sympathy for the doctor. Relief from joint problems, backache, and headaches and migraine are three of the top 10 reasons people see their doctor—but doctors have a narrowing field of possibilities to work with, and it got narrower once opioids became a no-go drug.

“What doctors are left with as this funnel gets narrower and narrower is antidepressants, and the prescription of antidepressants for people with chronic pain is on the rise,” said Tamar Pincus from the University of Southampton, one of the Cochrane researchers.

In the beginning

How were antidepressants ever considered for pain relief? Chronic pain and depression are often fellow travelers. Around 10 percent of the adult US population has been diagnosed with depression, and as many as 90% of them report chronic pain.2

This suggests that depression and pain have psychological and biological similarities, as the clinical definition of chronic pain suggests: “Chronic primary pain has no clear underlying condition, or the pain (or its impact) appears to be out of proportion to any observable injury or disease.”3

Leading psychiatrist Sir Simon Wessely put it more prosaically. “Many chronic pain sufferers have mental health disorders, such as anxiety and depression,” he wrote in a newspaper article.

The biological connection focused on serotonin, a neurotransmitter. A serotonin imbalance was suspected as a cause of depression—a theory now discredited—and its dysregulation was also a factor in chronic pain.

Early studies of the pain-relieving qualities of antidepressants seemed to support the theory. In one, back and shoulder pain eased “significantly” when the depressed patient took duloxetine,4 while another study concluded that the antidepressant had a major impact on pain severity, although 20 percent of the patients suffered from insomnia as a consequence.5

Only SNRI antidepressants, such as duloxetine, reduced pain; the more common SSRIs (selective serotonin reuptake inhibitors) didn’t have the same effect, according to a review by US Pharmacist.

Ties that bind

Unfortunately, the evidence can’t be trusted. When researchers from the Sydney School of Health reviewed published studies of antidepressant use for pain relief, they discovered that 45 percent of them had direct ties to the pharma industry. The manufacturer of the antidepressant had paid for the research and was likely to have influenced the result.6

Of the studies influenced by drug company funding, 68 percent had reviewed SNRIs, which is probably why the family of antidepressants is considered the most effective painkiller.

Just as the Cochrane reviewers found, the Australian team couldn’t see any clear evidence that antidepressants work as painkillers, and there was only a possibility that the SNRIs might ease back pain, pain after surgery, fibromyalgia and neuropathic pain. In an earlier study, the same researchers said the evidence that SNRIs helped ease any pain was just not there.7

None of this is good news for the chronic pain sufferer—and with a quarter of the US adult population experiencing long-lasting pain, it’s a problem that needs resolving. More of us will eventually be sufferers; by 2050, an estimated 843 million people around the world are expected to have low back pain, a 36 percent rise over today’s figures.8

It’s clear that drug-based medicine doesn’t have any answers to the epidemic of chronic pain. But that doesn’t mean there aren’t solutions (see below), it just means your first port of call shouldn’t be the doctor.

What you can do instead

Doctors should forget the drug approach altogether, says NICE. Instead, they should be encouraging the chronic pain sufferer to try exercise programs, stay active and even consider “thought therapies” such as CBT (cognitive behavioral therapy).

Here are some non-drug approaches that could ease chronic pain:

  • Medical marijuana: Medical marijuana has become one of the most popular ways to treat pain, and it’s justified, to an extent. One major review has found that it offers short-term pain relief.1
  • TENS (transcutaneous electrical nerve stimulation): TENS delivers small shocks through patches placed on the skin. The electrical impulses can relieve pain. According to one review, it’s the most promising treatment for arthritis of the knee.2
  • Exercise: Core-stabilizing and core-strengthening exercises can help relieve low back pain,3 and they’re especially effective if complemented with several sessions of Pilates every week.4
  • Diet: A diet that eliminates nightshades and restricts inflammatory foods such as red meat and refined carbohydrates can reduce pain levels. One study found that an anti-inflammatory diet reduced symptoms of osteoarthritis.5
  • Cognitive behavioral therapy (CBT): CBT teaches you to think differently about pain and gives you ways to cope. One study of back pain sufferers concluded that it was a more effective therapy than conventional care, as was mindfulness meditation.6
  • Body therapies: Occupational therapy, which teaches you to do everyday tasks differently, and physical therapy, which teaches exercises that stretch and strengthen the body, can reduce pain. A review of 76 studies of occupational therapy found that it effectively reduced shoulder pain,7 while physical therapy eased lower back pain.8
  • Acupuncture: Acupuncture is such an effective, and proven, pain reliever that doctors are advised to recommend it to patients, although researchers say the evidence is patchy and contradictory. One review found that it was very effective in relieving dental pain but that results weren’t so conclusive about the treatment of chronic pain and back pain.9
  • Aromatherapy: Aromatherapy is an ancient therapy that uses aromatic plants and essential oils to treat a range of conditions. One review found that it reduces anxiety and labor pains.10
  • Biofeedback: Biofeedback is a way to “read” your body and help influence heart rate, breathing and muscle tension. One review of 21 studies found it reduced pain intensity as well as depression, disability and muscle tension in the short and long term.11
  • Hypnotherapy: Hypnotherapy alters our awareness levels and helps us respond differently to stimuli. It is a “viable” way to manage pain, one study concluded, and should be considered as a non-drug option.12
  • Reiki: Reiki is an energy healing system that uses the energies around us to heal, de-stress and relax. One review of four studies concluded it is an effective way to relieve pain.13

Bryan Hubbard




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Main story
  1. Cochrane Database Syst Rev, 2023; 5: CD014682
  2. Am J Public Health, 2005; 95: 998–1000
  3. BMJ, 2021; 373: n907
  4. J Psychiatr Res, 2005; 39(1): 43–53
  5. J Clin Psychopharmacol, 2004; 24(4): 389–99
  6. BMJ, 2023; 380: e072415
  7. BMJ, 2021; 372: m4825
  8. Lancet Rheumatol, 2023; 5(6): e316–29
What you can do instead
  1. Ann Intern Med, 2022; 175(8): 1143–53
  2. Osteoarthritis Cartilage, 2015; 23(2): 189–202
  3. BMC Musculoskelet Disord, 2021; 22(1): 998
  4. J Orthop Sports Phys Ther, 2022; 52(8): 505–21
  5. Aging Clin Exp Res 2019; 31(6): 807–13
  6. JAMA, 2016; 315(12): 1240–9
  7. Am J Occup Ther, 2017; 71(1): 7101180020p1–11
  8. J Orthop Sports Phys Ther, 2021; 51(11): CPG1–60
  9. Ann Intern Med, 2002; 136(5): 374–83
  10. Ethiop J Health Sci, 2020; 30(3): 449–58
  11. Int J Behav Med, 2017; 24(1): 25-41
  12. J Am Psychiatr Nurses Assoc, 2020; 26(2): 157–61
  13. Complement Ther Clin Pract, 2018; 31: 384–87
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