Ketamine: Another Pandora’s Box or Viable Treatment for Pain?

In the wake of the opioid crisis, some physicians are seeking to utilize ketamine, a highly addictive drug, to treat chronic pain and depression. Ketamine is a generic name for Ketalar (ketamine hydrochloride) and belongs to a class of drugs known as dissociate anesthetics. Ketamine’s FDA label warns of the potential emergence of psychological issues with potentially dangerous drug interactions with barbiturates and narcotics. Ketamine has already proven its high potential for abuse and is well-known as a “recreational drug,” “club drug,,” and “date rape drug” due to its hallucinogenic and dissociative effects.

Its Chemistry

Ketamine’s chemical structure is similar to phencyclidine, otherwise known as PCP or“angel dust,” and reportedly causes a trance-like state. Ketamine targets and blocks the N-methyl-D-aspartate (NMDA) receptor which is responsible for the pharmacologic properties. By blocking this NMDA receptor, ketamine does not target the same brain activities as antidepressants like fluoxetine (Prozac), venlafaxine (Effexor), and sertraline (Zoloft). Ketamine is eliminated through the kidneys with a half-life of two-to-three hours but continues to have a prolonged effect after elimination.

Treatment of Chronic Pain

Ketamine is prescribed as “off –label” for chronic pain and has not undergone rigorous clinical trials for the treatment of neuropathic chronic pain. It is certainly not the first- or second-line treatment for neuropathic pain. Certain studies recognize that the drug could be utilized to address severe neurological conditions like complex regional pain syndrome (CRPS) and fibromyalgia with severe reservations.

Niesters, in Ketamine for chronic pain: risks and benefits, Br. J. Clin. Pharmacol Feb 2014; Vol. 77(2), pg. 357-367, studied treatment of various chronic pain syndromes by using ketamine. The study concluded that short-term infusions provided potent analgesia during administration only, while prolonged infusion (four to 14 days) demonstrated effects up to three months following infusion. The study documented numerous side effects (psychedelic symptoms, hallucinations, memory defects, panic attacks, nausea/vomiting, somnolence, cardiovascular stimulation, and hepatoxicity) and, of concern, increased recreational use of ketamine. The study recommended severe limitation of ketamine to those individuals with severe neuropathic pain and as a last resort after all other treatments failed. Other authorities, including the American Society of Regional Anesthesia and Pain Medicine, urge caution on using ketamine to treat chronic pain as the risks may not outweigh the benefits received by the treatment. The Centers for Disease Control and Prevention (CDC) and American Medical Association (AMA) agree that chronic pain should be addressed in a multimodal disciplinary approach inclusive of psychological treatment and cognitive behavioral treatment; yet, many still seek the quick and easy path to eliminate pain. Ketamine remains only authorized by the FDA for an anesthetic for diagnostic and surgical procedures, but it is undeniable that the FDA, by failure to comment, has allowed the rampant “off-label” use for chronic pain and depression.

Treatment of Depression

Several small clinical trials (sample size 30-50 people) suggest that ketamine could be an effective therapy for depression. For example, Nolan Williams, Boris Heifets and Christine Blasey, in Attenuation of Antidepressant Effects of Ketamine by Opioid Reception Antagonism, American Journal of Psychiatry, August 29, 2018, concluded that,

“[t]he findings suggest that ketamine’s acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.”

The researchers caution that repeated use of ketamine could lead to increased risk for dependency as ketamine remains highly addictive with severe withdrawal symptoms. These nascent studies reveal that ketamine’s usage to treat depression is experimental presently and should not be authorized. Concerns remain as to the impact of withdrawal on individuals already severely depressed, and we will likely see, as in chronic pain studies, an increase in recreational usage, as well as a potential corresponding increase in civil (and criminal) claims involving ketamine.

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