A recent study provides additional evidence that ketamine may be effective in treating severe forms of depression. Conducted across four major U.S. medical institutions, the study found that ketamine infusions led to significant improvements in depressive symptoms, including suicidality, in individuals who had not responded to conventional treatments. The research is part of a larger project that seeks to uncover blood-based biomarkers of treatment response.
The new findings were recently published in the Journal of Affective Disorders.
The Driving Force Behind the Study
Major depressive disorder is a common condition globally, affecting a significant portion of the adult population. It’s not just a health issue but also has considerable economic implications due to its role in long-term disability and associated costs.
Traditional antidepressants and mood stabilizers have shown limited effectiveness. Only a portion of depression patients achieve remission with these treatments, and many do not respond at all. This situation is particularly challenging in bipolar disorder, where depression is a predominant issue, but few effective pharmacological treatments are available.
Intravenous ketamine, a potent NMDA antagonist, has shown promise in several controlled trials. It has demonstrated effectiveness in treating symptoms of depression in patients who have not responded to other treatments. Notably, ketamine’s effects are rapid, and it has shown a potential in reducing suicidal ideation.
Despite the encouraging results with ketamine, there’s a lack of understanding about who benefits most from this treatment. Identifying predictors of response, including potential blood-based biomarkers, could significantly enhance the effectiveness of treatment by targeting those most likely to benefit.
“The main purpose of the study is to find a blood test that can help predict who will benefit from intravenous ketamine,” explained study author Sagar V. Parikh, a professor of psychiatry at the University of Michigan. “This first publication looked at whether three infusions were capable of causing remission (it was in 52% of people in less than two weeks, which is wonderful news). We believe that ketamine will be a standard and highly effective treatment for people who don’t respond to traditional antidepressants.”
Study Design and Methodology
The “Bio-K” study, an open-label, single-arm trial, was conducted from May 2017 to March 2020 and involved participants from the Mayo Clinic, the University of Michigan, Johns Hopkins University, and Pine Rest Christian Mental Health Services. To participate, individuals had to be between 18 and 65 years old and diagnosed with major depressive disorder or bipolar I or II disorder. Importantly, they needed to have a history of treatment resistance, meaning traditional antidepressants had failed them.
During the study, participants remained on their existing medications. Researchers meticulously monitored their symptoms using a range of measures. The Montgomery Åsberg Depression Rating Scale (MADRS) was employed to assess depressive symptoms, while the Beck Scale for Suicidal Ideation (BSS) gauged suicidal thoughts. Anhedonia, the inability to feel pleasure, was measured using the Snaith-Hamilton Pleasure Scale (SHAPS). Cognitive function and mood elevation risks were also evaluated.
Participants received three ketamine infusions over an 11-day period, with careful monitoring of their cardiac activity and side effects. The doses were administered over 40 to 100 minutes, depending on individual responses and side effect concerns.
Key Findings of the Study
Approximately 52% of the study’s participants achieved remission, which was determined by a marked reduction in their scores on the MADRS. This result was particularly striking given that all participants had previously not responded to traditional treatments for depression.
The researchers also observed a substantial decrease in suicidal thoughts among participants. At baseline, 81% of the participants had notable suicidal ideation. Following the ketamine treatment, there was an average reduction in BSS scores of 67%, with two-thirds of the participants experiencing at least a 50% reduction in suicidality.
The results indicated a significant decrease in anhedonia, with 92% of participants showing abnormal SHAPS scores at baseline, which reduced to 41% post-treatment. This reduction suggests that ketamine not only alleviated depressive symptoms but also helped improve the overall quality of life and emotional well-being of the participants.
The findings of this study corroborate previous research demonstrating the antidepressant properties of ketamine. Crucially, the study provides a substantial participant base, paving the way for future analyses focused on identifying biological markers associated with treatment response
“There is great hope that ketamine is a new and highly effective treatment, and that it might be possible to find a blood test to tell us if ketamine is the right choice for a particular person,” Parikh told PsyPost. The long-term objective of this line of research is “to find fast and effective treatments for depression, so people don’t have to wait months and use trial and error to find the right treatment.”
Regarding the side effects, the Ketamine Side Effects Scale (KSES) captured various side effects during and after the infusions. Although some participants experienced notable side effects during the infusion, these largely subsided by 60 minutes post-infusion. The study reported only one serious adverse event related to ketamine administration, involving a case of hypoglycemia in a participant with diabetes.
“The treatments were extremely well-tolerated,” Parikh said. “We also tried to see if even slower infusion would make it more tolerable, and if the speed of infusion (slow at over 100 minutes versus standard over 40 minutes), and found that slower did not have any advantages.”
Caveats
However, as promising as these results are, there are limitations to consider. The study did not include a control group, making it difficult to compare the effects of ketamine against a placebo or other treatment. The open-label nature of the trial also means that both researchers and participants knew they were receiving ketamine, which could introduce bias.
“These are the clinical findings, we are still waiting to publish our reports on various biomarkers found in the blood,” Parikh explained. “Those findings will come out over the next year.”
The study, “Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression“, was authored by Sagar V. Parikh, Jennifer L. Vande Voort, Anastasia K. Yocum, Eric Achtyes, Fernando S. Goes, Louis Nykamp, Balwinder Singh, Daniela Lopez-Vives, Cortney E. Sera, Daniel Maixner, Vijay Tarnal, Jennifer Severe, Steven Bartek, Susannah J. Tye, Jose Rico, Cynthia J. Stoppel, Alexis Becerra, LeAnn Smart, Christina R. Miller, Mark A. Frye, John F. Greden, and William V. Bobo.
