Ketamine is a medication that was patented in 1969 and put to medical use in humans in the 1970s. It has had many roles over the years, including as a general anesthetic in adults and children for surgery, a drug used in veterinary medicine for pain and anesthesia, as well as alternative roles abroad as a drug used in regression therapy and “spiritual discovery.” It has also been used as recreational drug in RAVEs in Europe and Canada and sold as Ectasy or MDMA.
Research on Ketamine’s use for chronic pain was first performed by Ronald Harbut, M.D., of Little Rock, Ark., sometimes called the father of Ketamine therapy who worked with Graeme Correll, B.E., M.B.B.S., of Australia. Harbut and Correll first successfully treated patients with intractable pain states in the 1990s, but it was not until 2002 that Dr. Harbut worked with the FDA to create a treatment protocol.
Dr. Harbut and Dr. Correll found that Ketamine was most effective for patients with burning, shooting pain that is neuropathic in nature and characterized as having a “centralized component.” Centralization of pain is an abnormal response and is characterized by changes that occur in the brain and the spinal cord as the result of a chronic peripheral painful stimulus. This process is potentiated by the mechanisms of “plasticity” and “wind up,” which ultimately result in a larger-than-normal receptive field in the brain. The exaggerated receptive field produces a greater-than-expected pain perception.
Examples of painful conditions that involve central sensitization are CRPS or RSD, post-herpetic neuralgia, causalgia, phantom limb pain, peripheral nerve injury and trigeminal neuralgia. Although many of these conditions may respond to Ketamine infusion therapy, most of the studies thus far have been performed on patients with CRPS or Complex Regional Pain Syndrome.
Ketamine’s mechanism of action is thought to be from its profound ability to block the NMDA receptor, the channel or gateway where a painful stimulus enters the central nervous system by way of the dorsal horn. It has been discovered that the longer a patient with centralized pain is exposed to Ketamine by way of infusion at the highest dose possible, the better the clinical outcome.
There are several approaches for Ketamine infusion for the treatment of neuropathic pain. In the United States, the treatment is administered as an inpatient in some facilities as well as outpatient in others. The inpatient method involves the patient’s admission to the hospital, where they are treated with 25 to 50mg of ketamine per hour for five days. The outpatient protocol varies, but it basically involves a one- to fourhour infusion of Ketamine at 25 to 300 mg per hour.
During the inpatient and outpatient infusions, a benzodiazepine is administered to avoid the negative side effects of Ketamine. The patient is continuously monitored and recovered before discharge. Outside the U.S., because it is not FDA-approved in the country, patients are placed into Ketamine comas for five to seven days. These patients are induced, intubated, ventilated and administered 500 to 700mg of Ketamine per hour.
The clinical research studies have shown success rates anywhere from 80 to 100 percent. The most effective method is the coma method followed by the inpatient and outpatient methods. One of the most concerning issues of the Ketamine infusion therapy is the failure of the pain resolution to last. Almost all patients treated with Ketamine infusion require the patient to return for a one- to two-day booster anywhere from two to six months following the initial treatment. The booster is an outpatient four-hour infusion of the patient’s greatest tolerated dose. Research is ongoing to resolve this issue and prolong the effects of the initial infusion.
In conclusion, Ketamine infusions are a welcome effective modality in the treatment of neuropathic pain syndromes. This treatment has shown amazing success in patients with the most intractable, unmanageable pain states where all other treatments have failed.