Ketamine and Other Promising Alternatives to Opioids

Ketamine may be a promising alternative to opioids

Pain expert Steven Richeimer, MD, believes ketamine should be more widely used as an alternative to opioids. Research has shown that in controlled doses and environments, ketamine can play an important role in human pain management.

Dr. Richeimer is Chief, Division of Pain Medicine and Professor of Anesthesiology & Psychiatry at the University of Southern California Keck School of Medicine. He recently prepared a lecture on this topic for the California Society of Anesthesiologists annual medical conference in April. Although the conference was canceled due to COVID-19 concerns, Dr. Richeimer graciously shared some of his lecture’s key takeaways with SpineUniverse.

Ketamine Background

Ketamine is an NMDA receptor antagonist, along with several other commercially available drugs including memantine, amantadine, and dextromethorphan. Ketamine is an old drug: synthesized in 1962, approved by the U.S. Food and Drug Administration (FDA) in 1970, and used as a field anesthetic during the war in Vietnam. It is still widely used as an anesthetic in human and veterinary practice, but it has gained notoriety as a recreational drug for its potentially dissociative effects.

How Ketamine Relieves Pain

There are several mechanisms by which ketamine may mitigate pain. Research suggests it can:

• Reduce central sensitization
• Reduce opioid-induced hyperalgesia
• Reduce opioid tolerance
• Inhibit serotonin and dopamine reuptake
• Reduce pain-induced depression

Ketamine in Current Medical Practice

Ketamine, in low doses, may be used postoperatively to reduce opioid use and decrease nausea and vomiting. In some cases it provides primary postop pain relief, particularly in patients who do not tolerate opioids.

Ketamine is also administered in infusion centers for patients with intractable pain from several conditions, including:

• Chronic regional pain syndrome
• Other neuropathic conditions
• Refractory headache

Oral ketamine can be prescribed for pain management, but it is not commercially available; prescriptions must be sent to compounding pharmacies. Physicians who have not previously prescribed ketamine may want to work with a pain management specialist who is familiar with the drug.

Risks and Considerations

All drugs, particularly powerful pain relievers, come with a long list of potential side effects. Ketamine is no exception, and therefore should be avoided in patients with:

• Severe cerebrovascular and cardiovascular diseases
• Psychosis or delirium
• Severe liver disease / hepatitis
• Active substance abuse
• Glaucoma / increased intraocular pressure
• Hyperthyroidism or pheochromocytoma

Other Promising Opioid Alternatives

NMDA receptor antagonists, not just ketamine, are being studied for their potential role as opioid alternatives. They increase dopamine release and block dopamine reuptake, which can confer numerous benefits in a range of conditions.

Consider amantadine, originally approved by the FDA in 1966 as an antiviral. It was later found to be useful in Parkinson’s disease treatment and as an analgesic in veterinary practice. Research published in Pain Medicine found that in young adults undergoing elective spine surgery, amantadine reduced fentanyl use during the procedure, reduced postoperative pain, and decreased morphine consumption.

Memantine, first synthesized in 1968, is FDA-approved to treat Alzheimer’s disease. It may improve memory, attention, language, and other systems affected by this form of dementia. Early research also suggests it may have a role in neuropathic pain – including mastectomy-related pain.

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