Targeted Non-Opioid Alternatives for Emergency-Department Pain Management

The researchers at San Francisco General Hospital reviewed the ED formulary and peer-reviewed evidence to compile a targeted list of non-opioid drugs for five common acute pain types—abdominal, back, chest, fracture and headache.

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Since the 1990s, loosely regulated opioid prescriptions sparked the first wave of the U.S. opioid crisis, driving clinicians to seek safer analgesics that balance efficacy with addiction risk and prompting policy reforms.

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The study was led by Akash Shanmugam, a UCSF medical student and first author, and Dr Kathy LeSaint, associate professor of emergency medicine at UCSF, both based at San Francisco General Hospital.

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The authors rated acetaminophen and ibuprofen as effective for all five pain categories. Ketamine was highlighted for chest pain; an SNRI for back pain; antipsychotics for headache and abdominal pain; and gabapentin for neuropathic pain. Genetic variability in opioid metabolism supports personalized selection.

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The review notes that psychotropic agents affect dopamine, serotonin, norepinephrine, glutamate and calcium-channel activity, influencing both sensory and emotional pain pathways. Gabapentin modulates calcium channels; antidepressants and antipsychotics regulate neurotransmitter release, potentially reducing central sensitization.

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Adopting these alternatives could lower opioid exposure while preserving analgesia. Matching drugs to specific syndromes and patient histories may curb central sensitization and address co-morbid sleep, anxiety and depression. Clinicians should discuss prior opioid use and individual concerns before prescribing.

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If adopted widely, the toolbox could shape hospital protocols and inform national pain-management guidelines, supporting broader efforts to curb opioid prescribing, reduce addiction-related morbidity, and improve patient safety in emergency care.

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Shanmugam emphasized that the aim was to create a concise, condition-specific toolbox for ED physicians, stressing that opioid reduction must not lead to under-treatment. LeSaint highlighted the need to review evidence and each patient’s prior opioid experience before prescribing, and noted that psychotropic agents modulate pain-related neural circuits.

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Both authors acknowledge opioids still have a therapeutic role and caution that alternatives require careful evidence appraisal and patient counseling to avoid implying pain is ‘all in the head.’ They stress any shift must be evidence-driven.

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• “create a very targeted list for specific pain conditions” — Akash Shanmugam, Medical Student, UCSF

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• “The desire to reduce opioids shouldn’t come at the expense of under-treating pain,” — Akash Shanmugam

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• “the enzymes that are responsible for metabolizing opioids can have different strengths in people” — Kathy LeSaint, MD

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• “Talking to them and asking about their prior experience with opioids prior to giving opioids can be really helpful in tailoring the pain regimen for that particular patient, for that particular pain syndrome,” — Kathy LeSaint

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