Many of you may follow the recent research in psychotropics, such as LSD, MDMA, and psilocybin for various mental health disorders. Ketamine, though used traditionally as an anesthetic, is commonly included in this group of drugs, and has some exciting new research for off-label use in the treatment of depression and also short-term pain management instead of opioids. For those of you who are following this research, or aware of it, this is a news release that was posted by Mass General on the dosing protocols for ketamine use for treatment-resistant depression. Please note, the administration of this protocol is intravenous (IV).
Study identifies 2 subanesthetic dosage levels of the anesthetic drug, ketamine, provides significant symptom relief to patients with treatment-resistant depression
A study led by Massachusetts General Hospital (MGH) investigators identifies two subanesthetic dosage levels of the anesthetic drug ketamine that appear to provide significant symptom relief to patients with treatment-resistant depression. In the October 2018 issue of Molecular Psychiatry, they describe finding that single intravenous doses of 0.5 mg/kg and 1.0 mg/kg were more effective than an active placebo in reducing depression symptoms over a three-day period. Two lower dosage levels that were tested did not provide significant symptom relief, although some improvement was noted with the lowest 0.1 mg/kg dose.
“Treatment resistance in depression is a major issue, with more than half of patients not responding adequately to standard, appropriate antidepressant treatment,” says Maurizio Fava, MD, executive director of the Clinical Trials Network & Institute in the MGH Department of Psychiatry and senior author of the Molecular Psychiatry paper. “There are only a few approved therapies that can help some patients with treatment-resistant depression, so we critically need more options to choose from.”
General anesthetic drug, ketamine, was used
Long used as a general anesthetic drug, ketamine has been found in several studies to rapidly relieve depression symptoms when given at low, subanesthetic doses. Most of those studies used a standard 0.5 mg/kg intravenous dose, leaving determination of the optimal dosage unclear. To investigate that question, the study tested four different ketamine dosages – 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg and 1.0 mg/kg – compared with an “active” placebo, a drug that induces side effects, the lack of which could lead participants to realize they are not receiving the medication being tested, potentially biasing their perception of symptom improvement.
Study enrolled 99 adults with treatment-resistant depression
The study enrolled 99 adults with treatment-resistant depression at 6research centers – MGH, Baylor College of Medicine/Debakey VA Medical Center, Icahn School of Medicine at Mt. Sinai, Stanford University School of Medicine, University of Texas/Southwestern Medical Center, and Yale University. Participants were randomized into five groups – the four dosage levels and the active control group, with neither they nor the research staff aware of group assignments – and continued taking their previously prescribed antidepressants during the study period.
Participants assessed with a standard depression rating scale
Participants were assessed with a standard depression rating scale the day they received the infusion and 2, 3, 5, 7, 14 and 30 days later. Additional instruments measured aspects of mood and suicidal thought. Dissociative symptoms such as memory loss and feelings of detachment from reality were assessed during and after ketamine infusion, and vital signs were measured after treatment and at all follow-up visits.
Participants receiving ketamine had significantly greater symptom improvement during the 3 days after infusion
On the standard depression scale, participants receiving ketamine had significantly greater symptom improvement during the 3 days after infusion than did those in the active control group. Comparison of dosage levels, after adjusting for multiple comparisons, found statistically significant improvement compared to the control group only for participants receiving 0.5 mg/kg and 1.0 mg/kg doses. The low 0.1 mg/kg dose produced significant relief only prior to adjustment, and the 0.2 mg/kg dose did not show any significant benefits. It is possible that the lack of efficacy at the 0.2 mg/kg level could reflect the small size of treatment groups and the fact that participants in that group tended to be more treatment resistant to begin with, the authors note.
Higher dose participants: benefits of ketamine treatment began to decrease on the third day after treatment
For most participants in the higher-dose groups, the benefits of ketamine treatment began to decrease on the third day after treatment and were no longer detectable after 5 days. There were no significant differences in the occurrence of adverse events among all study participants.
A tailored treatment plan that may include ketamine
Co-author Cristina Cusin, MD, who directs the MGH Psychiatry ketamine clinic, says, “These results support the clinical observation that one size – in this case the most studied dose of 0.5 mg/kg – does not fit all, as some patients may require a lower-than-average dose; and each patient needs a tailored treatment plan that may include ketamine, together with other medications and talk therapy. We still do not understand which factors play a role in determining lack of response to treatments or which is the best possible strategy for patients suffering from severe depression.”
‘Study also suggests that even lower doses may be effective in some patients’
Fava, the Slater Family Professor of Psychiatry at Harvard Medical School, adds, “Along with supporting the efficacy of intravenous ketamine for patients with treatment-resistant depression, our study also suggests that even lower doses may be effective in some patients. Further investigation should examine the efficacy of repeat doses of ketamine, as well as whether higher doses may require less frequent administration.”
News Release from: Massachusetts General Hospital
Razi Berry is the founder and publisher of the journal Naturopathic Doctor News & Review that has been in print since 2005 and the premier consumer-faced website of naturopathic medicine, NaturalPath. She is the host of The Natural Cancer Prevention Summit and The Heart Revolution-Heal, Empower and Follow Your Heart, and the popular 10 week Sugar Free Summer program. From a near death experience as a young girl that healed her failing heart, to later overcoming infertility and Chronic Fatigue Syndrome and Fibromyalgia through naturopathic medicine, Razi has lived the mind/body healing paradigm. Her projects uniquely capture the tradition and philosophy of naturopathy: The healing power of nature, the vital life force in every living thing and the undeniable role that science and mind/body medicine have in creating health and overcoming dis-ease. Follow Razi on Facebook at Razi Berry and join us at Love is Medicine to explore the convergence of love and health.