Slow Sparse Ketamine Infusions Show Promise For Resistant Depression Interview with:
Theodore Henderson, MD, PhD
Neuroluminance Ketamine Infusion Centers What is the background for this study? What are the main findings?

Dr. Henderson: Depression is a widespread problem. Psychotropic medications or therapy are the standard treatments, but they are often disappointing. Some studies have shown that the response rate to antidepressant medications is only 12-17% better than placebo response rate. Newer non-pharmacetical treatments, like transcranial magnetic stimulation, appear to have only a 50% response rate at best. The seminal study by Berman and colleagues in 2000 showed that sub-anesthetic dose infusions of the anesthetic, ketamine, produced a rapid antidepressant response. Many clinics across the United States focus on these rapid effects.

Our clinic has been treating patients with treatment-resistant depression (defined as failing five or more antidepressants) for over three years. Our response rate is 80% based on multiple depression rating scales. We report here on 100 of the over 300 patients in our clinic who agreed to share their data in a research study. We treated patients with ketamine infusions no more frequently than once per week, unlike the clinical studies and many other ketamine clinics. We found our patients did equally well or better and received fewer treatments.

The neurobiology of ketamine and its mechanism of action hold the key. Ketamine is a potent activator of the growth factor, brain derived neurotrophic factor (BDNF). This growth factor reverses the damage that depression causes to the brain – loss of synapses, dearborization of dendrites, and neuronal death. Ketamine’s ability to activate BDNF over time is responsible for a persistent antidepressant effect upon the brain. What should clinicians and patients take away from your report?

Dr. Henderson: The striking difference between the formal research studies of ketamine and the real-world experience of our patients in our clinic is that ketamine can be a lasting solution to depression. Most clinic studies focus on single infusions or on giving multiple infusions over a brief period of time.

Our study also challenged several false beliefs about ketamine. First, many assert that a patient must hallucinate in order to derive antidepressant benefit from ketamine. This assertion is completely false. While 80% of our patients experience clinical improvement, only one patient has experienced hallucinations in over three years of service.

Second, the American Psychiatric Association warns of the risk of addiction with ketamine infusion therapy. Despite the APA warning that ketamine clinics could be setting off a firestorm of ketamine abuse/addiction in the United States, it seems ironic that none of our patients have pursued getting “extra” infusions. Indeed, multiple patients have approached us about getting a refund on the unused portion of a treatment package, citing that they had no need for additional ketamine. Now, while the multiple of “anecdote” is not “data”, our clinical experience is that patients undergoing our protocols do not become addicted to ketamine and the “slippery slope” from treating depression to creating a ketamine addiction is not so precipitous as Newport and colleagues (2015) would, in absence of real-world experience and in the presence of significant commercial affiliations (see disclosures – Newport et al., 2015), lead us to believe. What recommendations do you have for future research as a result of this study?

Dr. Henderson: I am encouraged by the recent work of Lenze and colleagues at my alma mater, Washington University in St. Louis, showing extended duration infusions of over 40 hours can lead to protracted antidepressant effects. This supports my assertion that “time on the receptor” is the key variable for activating BDNF with ketamine. Further work on how to maximize the benefit at the level of BDNF is encouraged. Is there anything else you would like to add?

Dr. Henderson: I am very concerned about the use of oral and intranasal ketamine out there. These methods deliver large doses of ketamine, but do not create that extended “time on the receptor” that is required for ketamine to ideally work. Oral and intranasal ketamine is also much less carefully supervised and the risk for misuse, abuse, or addiction is therefore higher. I have also seen a much higher frequency of bladder-related complications with intranasal ketamine. None of our infusion patients have developed ulcerative cystitis or other bladder-related complications, but I have heard of numerous intranasal ketamine patients in the Colorado area developing cystitis. Thank you for your contribution to the community.


Year : 2016  |  Volume : 11  |  Issue : 2  |  Page : 195-2
Practical application of the neuroregenerative properties of ketamine: real world treatment experience

Theodore A Henderson M.D., Ph.D.
Neuro-Luminance, The Synaptic Space, Neuro-Laser Foundation, Centennial, CO,


Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Dr. Theodore Henderson (2016). Slow Sparse Ketamine Infusions Show Promise For Resistant Depression

Last Updated on March 21, 2016 by Marie Benz MD FAAD