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Ketamine Isn't Just for Pets and Ravers Anymore; People Living in Extreme Pain Are Trying It as a Remedy

Infusions of ketamine now represent last-resort therapy for those with the intractable disease known as complex regional pain syndrome.

Ketamine has captivated physicians and teens ever since 1970 when the FDA approved the drug as a surgical anesthesia, and young adults started getting high on it. First marketed as a veterinary anesthetic, ketamine -- which is chemically related to PCP and encourages psychological and physical dependence -- quickly caught on with drug abusers. By 1981 the U.S. Department of Health and Human Services recommended ketamine's reclassification as a controlled substance, but the DEA rejected the idea until 1992 when it received 775 reports of ketamine abuse, including veterinary clinic burglaries and hospital emergency room visits.

Despite an association with date rape and other hallucinatory drugs, infusions of ketamine now represent last-resort therapy for those with the intractable disease known as complex regional pain syndrome. The only drawback to treatment is patients literally may be betting their lives against this unorthodox, and potentially excessive, use of the drug.

"It's a crappy disease," said Philip Getson, clinical associate professor of neurology at Drexel University College of Medicine in Philadelphia. The syndrome ranks No. 1 in painful chronic conditions, according to the McGill Pain Index, and its symptoms include unbearable burning and sensitivity, muscle spasms, inflammation and problems with concentration and memory.

Like many pain management experts and despite the dearth of controlled studies, Getson uses ketamine off label. The most powerful of a set of anesthetics known as the NMDA (for N-methyl-D-aspartate) antagonists, ketamine blocks the sensitization process in the central nervous system, allowing pain cells to normalize.

Despite its awful symptoms, complex regional pain syndrome (also called reflex sympathetic dystrophy) remains difficult to diagnose. While the nonprofit RSDHope estimates 1.5 to 3 million with the syndrome in the United States, Getson believes that's a gross undercount, and that the true number is closer to 6 million, with women experiencing it disproportionately.

Plus, disagreement over number and type of diagnostic criteria (i.e. should statisticians factor in fibromyalgia as an indicator) can hurt recruitment for trials, said Jim Broatch, executive director of the RSD Syndrome Association. "Insurers don't want to diagnose it because it's costly to treat."

That reluctance echoes on the treatment side, as promising therapies involving ketamine have faced obstacles. "The FDA has taken a hands-off attitude [on ketamine]," says Getson, referring to the agency's trend toward less control of off-label use. Randall S. Stafford, associate professor at the Stanford Prevention Research Center in Palo Alto, Calif., believes that laxness discourages evidence-based practice -- medicine's gold standard. The option of off-label use sends the wrong message to drug manufacturers: Why bother conducting hard, costly studies on pharmaceutical products already in the pipeline if later you can seek approval for secondary applications and run clinical trials that are much cheaper, simpler -- and patient centered?

Enmeshed in the conflict between investigational science and sympathetic intervention is ketamine researcher Dr. Anthony Kirkpatrick, chairman of the Scientific Advisory Committee of the Tampa, Fla.-based RSD Foundation. Kirkpatrick performs three-day, low-dose outpatient procedures using ketamine. But he reserves a sort of secret weapon, the "ketamine coma cure" -- a high-risk procedure in which patients placed in a medically induced coma receive a continuous five-day, 600-mg-to-900-mg infusion -- for RSD victims with "catastrophic" conditions and "no alternative, no recourse."

"Many are suicidal," Kirkpatrick says, musing over the ethical implications of denying possible relief in those circumstances. Is it morally correct, for example, to randomize patients into two groups (one group receiving ketamine, the other put on temporary hold) or to administer a placebo or a different anesthesia such as propofol for the sake of science?

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