Two well-controlled studies demonstrate the long-tem benefits of outpatient ketamine infusions.

One study is from the Netherlands and the other is from the USA




Title: Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1

Marnix J. Sigtermansa, Jacobus J. van Hiltenb, Martin C.R. Bauera, M. Sesmu Arbousc, Johan Marinusb, Elise Y. Sartona, Albert Dahana


Published in the October 2009 issue (Vol. 145, Issue 3, Pages 271-272)

"We conclude that CRPS-1 patients with severe pain treated with 4days of continuous infusion of low-dose ketamine using an individualized stepwise tailoring of dosage have a clinically relevant reduction in pain lasting for 11weeks. Although the incidence of side effects in the treatment week was high, they were relatively mild and well accepted by the patients and disappeared upon the termination of infusion. In contrast to pain, there was no improvement in functional status."






Title: Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study





Robert J. Schwartzman, MD

Guillermo M. Alexander, Ph.D.

John R. Grothusen, PhD.

Terry Paylor RN

Erin Reichenberger MS

Marielle Perreault BS

This recent controlled study with a relatively low-dose ketamine (maximum 25 mg/hour) in an outpatient setting demonstrated a statistically significant (p<0.05) reduction in many pain parameters. The study also demonstrates the importance of higher doses ketamine for treating CRPS. This is the first study utilizing an active placebo as a control.

The report is published in PAIN.


Volume 147, Issue 1, Pages 107-115 (15 December 2009)


Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. The pathophysiology of CRPS is not known but both clinical and experimental evidence demonstrate the important of the NMDA receptor and glial activation in its induction and maintenance. Ketamine is the most potent clinically available safe NMDA antagonist that has a well established role in the treatment of acute and chronic pain. This randomized double-blind placebo controlled trial was designed to evaluate the effectiveness of intravenous ketamine in the treatment of CRPS. Before treatment, after informed consent was obtained, each subject was randomized into a ketamine or a placebo infusion group. Study subjects were evaluated for at least 2weeks prior to treatment and for 3months following treatment. All subjects were infused intravenously with normal saline with or without ketamine for 4h (25ml/h) daily for 10days. The maximum ketamine infusion rate was 0.35mg/kg/h, not to exceed 25mg/h over a 4h period. Subjects in both the ketamine and placebo groups were administered clonidine and versed. This study showed that intravenous ketamine administered in an outpatient setting resulted in statistically significant (p<0.05) reductions in many pain parameters. It also showed that subjects in our placebo group demonstrated no treatment effect in any parameter. The results of this study warrant a larger randomized placebo controlled trial using higher doses of ketamine and a longer follow-up period.



Patients and some physicians wrongly believe we need FDA (Food & Drug Administration) approval for the ketamine coma procedure in order for patients to receive reimbursement for this expensive and high-risk treatment.

There will never be FDA approval for the ketamine coma procedure to treat CRPS no matter how effective and safe the procedure. This issue needs to be viewed in relation to the problems and conflict of interest associated with the FDA approval process.

In the United States, the FDA will never approve a disease specific indication for ketamine such as CRPS because there is no patent protection and, therefore, no money to be made by a drug company in going forward with the FDA approval process for a specific disease state / diagnosis.


If there is no money to be made by drug companies, there is no incentive for them to seek FDA approval. Therefore, there is no financial incentive for the FDA to approve ketamine because more than 60% of FDA’s budget for approving drugs comes from drug companies.

Learn more ......   FDA


In effect, the FDA has already approved ketamine to treat CRPS. Thirty years ago, the FDA approved ketamine for a specific route of administration (IV) and dosage range up to and including general anesthesia to treat breakthrough pain regardless of the underlying disease state / diagnosis.


Third party payers (e.g., insurance companies, governments) are likely to reimburse patients for ketamine treatments with the publication of control studies like those referenced above.


 It is unlikely that a study with an active placebo control (e.g. midazolam, fentanyl) conducted in the ICU will ever take place from an ethical standpoint given that ketamine has already been proven effective at a low dose for treating CRPS on an outpatient basis and, as noted above by Schwartzman et al, higher doses of ketamine are likely to be more effective. Under this circumstance, many patients with CRPS would not volunteer to be intubated and mechanically ventilated for 5 days in the ICU with an active placebo control instead of ketamine. Moreover, an active placebo would likely worsen CRPS. Schwartzman et al showed no beneficial effects of midazolam on CRPS and other studies have shown that opioids (fentanyl) can cause hyperalgesia.  

Recently, NATIONAL GEOGRAPHIC presented a documentary on the early research on hallucinogens before the US GOVERMENT banned the research on LSD. In the 45-minute video researchers provide valuable information. For example, suggestions are given on how to achieve a high dose of a hallucinogen without causing adverse hallucinations. The video "Inside LSD" has been uploaded to the Foundation's server at the following site:



Anthony  Kirkpatrick, MD, PhD

The International Research Foundation for RSD / CRPS

December 22, 2009