Ketamine: A Different Approach
Dore, J., Turnipseed, B., Dwyer, S., Turnipseed, A., Andries, J., Ascani, G., Monnette, C., Huidekoper, A., Strauss, N., & Wolfson, P. (2019) Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy, Journal of Psychoactive Drugs, 51(2), 189-198.
Ketamine’s potential to treat psychiatric and psychological problems was identified in the 1970’s, but it wasn’t until the mid 2000’s that psychiatrists began administering ketamine in conjunction with psychotherapy. This article explores how we can leverage ketamine’s ability to expand openness and provide a break from the normal thinking mind to enhance psychotherapy and produce more meaningful outcomes than with ketamine alone. An analysis of over 200 patients suggests ketamine assisted psychotherapy is effective in treating depression, anxiety, PTSD, and substance use:
- Patients with severe symptoms demonstrated significant improvements in well-being scores and reductions in anxiety, depression, PTSD, and substance use scores.
- Patients with developmental trauma demonstrated the greatest improvements in anxiety and depression scores.
- Older age correlated with greater improvement in depression and anxiety.
- More visits and longer duration of treatment correlated with greater improvements in depression.
Calabrese, L. (2019). Titrated Serial Ketamine Infusions Stop Outpatient Suicidality and Avert ER Visits and Hospitalizations, International Journal of Psychiatry Research 2(6), 1-12.
219 adults and adolescents with treatment resistant depression and other co-occurring psychiatric disorders received up to 6 ketamine infusions at real world outpatient clinic. Of the patients who presented with suicidal ideation, suicidal ideation was significantly lower in 79% and ceased completely for 59%. No patients attempted or completed suicide, visited the ER, or were hospitalized. Depression scores decreased significantly, although the decrease in suicidality was observed even in patients who remained depressed.
Feder, A., Parides, M.K., Murrough, J.W., Perez, A.M., Morgan, J.E., Saxena, S., Kirkwood, K., aan het Rot, M., Lapidus, K.A., Wan, L.B., Iosifescu, D., & Charney, D.S. (2014). Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial, JAMA Psychiatry, 71(6), 681-688.
This small-scale study explored the possibility of using ketamine to treat symptoms related to Post Traumatic Stress Disorder (PTSD), a condition for which existing pharmacological interventions are rarely effective. This small-scale study showed that PTSD symptom severity significantly and rapidly improved after a single IV ketamine infusion. Benefits were maintained for at least two weeks in several patients. Participants also experienced a reduction in depressive symptoms, but the effect on PTSD was more significant.
Wei Y., Chang L., Hashimoto K. (2020). A historical review of antidepressant effects of ketamine and its enantiomers. Pharmacology Biochemistry and Behavior, 190 , art. no. 172870.
This paper covers the historical context around ketamine use in clinics to treat depression and explores the important discoveries in mood research regarding ketamine. While ketamine has been used off-label in the United States for treatment-resistant depression, the FDA and European Commission recently approved a nasal spray in 2019.
Despite its potential, there are concerns about the efficacy and long-term safety of the ketamine. There is a growing body of data suggesting that certain organic configurations, called enantiomers, of ketamine may have different antidepressant effects. Specifically, the enantiomer (R)-ketamine has been shown to have greater potency, longer lasting antidepressant effects, and fewer detrimental side effects than (R,S)-ketamine and (S)-ketamine. More research is needed to understand the differences between these enantiomers.
Ketamine interacts with several protein pathways in the brain important for memory, plasticity, and learning. Below are several key highlights outlined in the paper:
- Ketamine has been shown to inhibit the NMDAR (N-Methyl-D-aspartate receptor), a glutamate and ion channel protein receptor found in neurons, resulting in antidepressant effects.
- Rapid-acting effects of ketamine are also dependent on the synthesis of BDNF (brain-derived neurotrophic factor), an important protein involved in the plastic changes related to learning and memory. Prolonged activation of BDNK-TrkB cascade is responsible for the long-lasting antidepressant effect of ketamine.
- Combined ketamine with rapamycin therapy may also lead to prolonged antidepressant effects. Rapamycin (mTOR) is a protein that serves as a core component of a protein called kinase that regulates cell growth, proliferation, motility, and survival.
- The transforming growth factor (TGF)-β1, a protein that performs many cellular functions, likely plays a role in antidepressant effects of (R)-ketamine and could be a novel therapeutic target for depression.
- Finally, ketamine might also influence the brain–gut–microbiota axis, a bidirectional link between the central nervous system (CNS) and the enteric nervous system (ENS) of the body. It involves direct and indirect pathways between cognitive and emotional centers in the brain with peripheral intestinal functions.
More on Ketamine Therapy
Over the past 20 years and in dozens of studies, ketamine has been shown to produce remarkably fast antidepressant effects. As a result, it has become a life-changing treatment for many suffering from treatment-resistant depression, MDD, PTSD and suicidal ideation.
More on Ketamine Research and Resources
Since the early part of this century, there have been mounds of research performed about the efficacy of ketamine. Here, you can access some of the most definitive pieces of ketamine research and resources. Educate yourself, get the facts.
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