Researchers Urge Caution on Ketamine Infusions

By Pat Anson, PNN Editor

With many chronic pain patients losing access to opioid medication, some are turning to ketamine as an alternative. Ketamine is approved by the FDA for depression, anesthesia and post-surgical acute pain, but a growing number of clinics provide off-label infusions of ketamine to treat difficult chronic pain conditions such as Complex Regional Pain Syndrome (CRPS).

Researchers at Duke University say doctors and pain patients should be cautious in their use of ketamine. In a study of nearly 300 patients who received ketamine infusions, over a third reported significant side effects such as hallucinations and visual disturbances.

The study findings were presented this week at the annual meeting of the American Society of Anesthesiologists (ASA).

"Despite the U.S. Food and Drug Administration's approval of ketamine for multiple uses, including general anesthesia and treatment of depression, the effects of using the drug at low doses to treat pain have not been extensively studied," said lead author Padma Gulur, MD, a  member of ASA's Committee on Pain Medicine and a professor of anesthesiology at Duke.

"Our research aimed to determine both short- and long-term side effects of low dose ketamine when used for pain treatment."

Gulur and her colleagues found 20 percent of the pain patients who used ketamine alone had side effects, while 15% experienced side effects from using ketamine in combination with other drugs.

Side effects directly linked to ketamine include hallucinations, vivid dreams, out-of-body experiences and unusual thoughts; while those who used ketamine and other drugs experienced sedation, visual disturbances and urinary dysfunction.

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"More than one in three patients reported significant side effects from ketamine infusions that required ongoing monitoring or resulted in discontinuation of therapy. More research on the impact of ketamine use for pain on the population is needed," said Gulur.

Guidelines from the ASA, the American Society of Regional Anesthesia and Pain Medicine, and the American Academy of Pain Medicine only support ketamine infusions for CRPS and short-term acute pain. There is weak or no evidence from clinical trials to support ketamine infusions for spinal cord injury pain, neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache or low back pain.

“Excluding CRPS, there was no evidence supporting ketamine infusions for intermediate or long-term improvements in pain," the guidelines warn.

The FDA recently approved a ketamine-based nasal spray to treat depression, even though 2 out of 3 short term trials failed to prove its effectiveness. The Spravato nasal spray was effective in a longer trial, but only when taken with a conventional antidepressant.

Because of the risk of abuse and side effects, Spravato can only be administered in a doctor’s office, where patients can be observed for two hours after taking a dose. A single dose will cost about $900. Spravato is not recommended for pain.

There is some debate in the medical community about whether ketamine is an opioid, because it acts on opioid receptors in the brain. Stanford researchers urge caution about the long-term use of ketamine until more can be learned about possible side effects such as addiction. Some depressed patients taken off ketamine have shown signs of withdrawal and became suicidal.  

A recent review of ketamine found that it was a “superb drug” for short-term medical procedures that require anesthesia and was relatively safe as a treatment for chronic pain.

“There is a wealth of evidence indicating the value of ketamine in the treatment of severe pain including conditions such as trauma, fractures, abdominal and flank pain, low back pain, and extremity pain,” said lead author Jorge Palacios, MD, an anesthesiologist at Kaweah Delta Medical Center in Visalia, CA.  

“It is safe and effective to use in combination with injectable nonsteroidal pain medications as well as opioids and has gained greater acceptance as concern has grown with regard to opioid use.”