A new study suggests that a range of medications, including antidepressants and antipsychotics, could serve as alternatives to powerful opioids for pain relief in emergency departments.
The review paper examined non-opioid medications available at San Francisco General Hospital and analyzed existing medical literature to identify which ones might provide effective pain relief.
Opioids have a strong track record of reducing pain effectively, but loose prescriptions with insufficient attention to their addictive properties led to the first wave of the US opioid crisis, which began in the 1990s.
Akash Shanmugam, a medical student at the University of California, San Francisco (UCSF) and first author of the study, said the goal was to “create a very targeted list for specific pain conditions” to help expand the “toolboxes” physicians use to treat patients.
The study provides recommendations for the most common types of pain seen in emergency departments: abdominal pain, back pain, chest pain, fracture pain, and headache.
Shanmugam and Dr. Kathy LeSaint, an associate professor of emergency medicine at UCSF and another author, agree that opioids still have a place in medicine. “The desire to reduce opioids shouldn’t come at the expense of under-treating pain,” Shanmugam said.
However, alternatives are increasingly important as physicians become more aware of potential long-term consequences. LeSaint noted that beyond concerns about opioid addiction and overdose, having a variety of pain medications is crucial because what works best varies from person to person, often due to genetic differences. For example, “the enzymes responsible for metabolizing opioids can have different strengths in people,” LeSaint explained.
The type of pain also determines which medications work best. Common pain relievers like acetaminophen and non-steroidal anti-inflammatory drugs (e.g., ibuprofen) showed potential for all pain types examined. Other drugs had more targeted applications: ketamine, an anesthetic, showed promise for chest pain; a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant helped with back pain; and several antipsychotics showed promise for headache and abdominal pain.
Psychotropic medications have long been used for pain relief as well as psychiatric symptoms. Shanmugam pointed out that gabapentin was first approved as a “really mediocre” drug for epilepsy but “is now used a lot for neuropathic pain.”
The mechanisms making these drugs effective for pain are complex and not fully understood, but Shanmugam said their efficacy likely relates to the fact that “neural circuits that create the sensation of pain are also involved in the emotional experience of pain and the distress it produces.”
Neurotransmitters like dopamine, serotonin, norepinephrine, and glutamate, which regulate mood, also play a role in pain sensation. Gabapentin alters neurotransmitter release via calcium channels, while antidepressants and antipsychotics regulate them more directly. These medications help maintain the nervous system at a more even keel by altering how neurotransmitters send signals within the brain.
“In chronic pain conditions, the nervous system can become highly sensitive, and it’s thought that antidepressants and antipsychotics can reduce this heightened sensitivity,” LeSaint said.
Drugs that improve mood can also help the body cope with pain. “Chronic pain is often linked to poor sleep, depression, anxiety, and fatigue,” according to LeSaint. Medications that improve sleep and reduce anxiety may make pain easier to manage physically and mentally.
While these alternatives may help some patients, LeSaint emphasized that doctors must review both the evidence and the individual patient’s situation. “Talking to them and asking about their prior experience with opioids before prescribing can be really helpful in tailoring the pain regimen for that particular patient and pain syndrome.”
When prescribing psychiatric medications, it is important to ensure patients understand this does not mean the pain is in their head, according to Shanmugam. “I’ve seen many clinicians use a basic science approach, explaining the overlap between pain mechanisms and emotional understanding of pain, which really helps reassure patients.”
