More Non-Opioid Drugs Recommended for ER Pain Relief
/By Pat Anson
Would you take an anti-depressant for back pain?
An anti-psychotic medication for headache?
What about an anti-anxiety drug for stomach pain?
Those are some of the non-opioid alternatives being recommended for pain relief in emergency rooms, as the healthcare industry continues to move away from using opioids for pain care.
The latest example is a study by researchers at University of California, San Francisco (UCSF), who recommend over a dozen non-opioid medications for five acute pain conditions commonly treated in emergency departments: back pain, abdominal pain, chest pain, fracture pain and headache.
The findings are published in the Western Journal of Emergency Medicine.
Researchers initially screened 246 clinical studies to prepare their non-opioid list, but narrowed it down to 23 of the most promising studies. First author Akash Shanmugam, a UCSF medical student, told The Guardian that the goal was to “create a very targeted list for specific pain conditions,” to add to the medical toolboxes used by ER physicians.
Many of the drugs that made the list, such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are already widely used for acute pain. But some of the selections are puzzling, as they are psychotropic drugs not typically used to treat pain.
For example, the anti-psychotic drug haloperidol is recommended for both headaches and abdominal pain. Haloperidol is usually prescribed for schizophrenia or acute agitation, and is sometimes used off-label for conditions like psychosis and Tourette's syndrome.
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is typically used to treat depression and anxiety, but UCSF researchers think it could be used for back pain.
Other oddities that made the non-opioid list are ketamine for chest pain, abdominal pain and headache; benzodiazepines for abdominal pain; and the anti-nausea drug metoclopramide for headaches.
Gabapentin would have made the list of non-opioid alternatives, but researchers decided the evidence was too weak to support its use for the five conditions they evaluated.
“Our findings hold significant implications for pain management approaches in the ED and public health efforts aiming to address the opioid epidemic. By providing alternatives to opioid prescriptions, this review supports efforts to reduce opioid overexposure in the ED while helping to manage patient pain,” researchers said.
“Encouraging the use of these alternatives aligns with broader initiatives aimed at optimizing pain management practices, improving patient outcomes, and contributing to the overall mitigation of the ED’s contribution to the opioid crisis.”
‘Made Me Feel Worse’
But are the drugs effective for pain? Posters on Reddit are skeptical that antidepressants and anti-psychotics would be helpful.
“This is ironic because codeine does a better job of making my brain quiet than any antidepressant I've tried so far,” said one poster. “I've never developed an addiction to codeine and it's also never induced suicidal thoughts, unlike a couple of the antidepressants I've tried. It also didn't make me so physically sick that I almost went to hospital, unlike the SNRI I stopped taking.”
“Tried tons of antidepressants for pain and depression, nothing worked in fact many made me suicidal. And then had tramadol prescribed for my back pain, low dose but my depression also improved a huge amount,” wrote another.
“These types of medications have made me feel worse than anything else I’ve ever taken. If I had to choose between pain and feeling like that again, I would choose the pain. But maybe that’s what they’re after since doctors don’t like prescribing pain medicine anyway,” said another Reddit poster.
“That's just ridiculous. Antidepressants and antipsychotics are not going to do anything at all to relieve pain,” said another. “The war on drugs has gone too far.”
But researchers say there’s frequently an overlap between physical and emotional pain that justifies the use of psychotropic drugs.
“Chronic pain is often linked to things like poor sleep, depression, anxiety, fatigue,” co-author Kathy LeSaint, MD, Associate Professor of Emergency Medicine at UCSF, told The Guardian. “In chronic pain conditions, the nervous system can become highly sensitive, and it’s thought that antidepressants and antipsychotics can maybe reduce this heightened sensitivity in the brain.”
Although the risk of addiction and overdose are often cited as reasons to use non-opioids, that risk is often exaggerated. A 2024 study found that the risk of long-term opioid use after being treated with intravenous opioids in the ER is quite low – less than two-tenths of one percent (0.19%).
That mirrors the findings of a 2017 Mayo Clinic study, which found that the risk of long-term opioid use is only 1.1% for ER patients — less than it is for patients treated in other medical settings.
Nevertheless, some pharmaceutical companies are betting that non-opioids are the future of pain relief. Eli Lilly today announced the purchase of 4E Therapeutics, a biotechnology company that’s developing MNK inhibitors, which block enzymes involved in the peripheral nervous system. 4E is the second non-opioid drug developer to be acquired by Lilly in a little over a year.
