Ketamine may be an effective treatment for severe depression, according to the results of a recently published clinical trial. The research, which was published in the peer-reviewed Journal of Affective Disorders, found that participants with major depressive disorder showed a significant improvement in symptoms including suicidality after receiving intravenous ketamine infusion therapy.
Major depressive disorder, also called clinical depression, is a mental health disorder characterized by persistent feelings of sadness and a loss of interest, according to information from the Mayo Clinic. The condition affects about 5% of the adult population globally, according to data from the World Health Organization, and can lead to difficulties in all aspects of life including home, work and school.
Depression is often treated with antidepressants and mood stabilizers, but these treatments have shown only limited success. Some patients do not respond to these options at all, while many others fail to achieve remission.
In prior studies, ketamine, which is commonly used as a dissociative anesthetic, has shown promise as a treatment for depression in patients who have not shown improvement with other therapies. The drug’s effects are particularly rapid and have shown the potential to reduce suicidal ideation in subjects with major depressive disorder.
The new research was conducted at four leading medical institutions across the United States as part of a larger study to determine blood-based biomarkers of depression treatment response. While the effects of ketamine can be dramatic, it is not well understood who can benefit the most from the drug. With the study, researchers hope to identify blood-based biomarkers to help predict who will benefit the most from ketamine therapy.
“The main purpose of the study is to find a blood test that can help predict who will benefit from intravenous ketamine,” study author Sagar V. Parikh, a professor of psychiatry at the University of Michigan, explained to PsyPost. “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.”
The study was conducted between May 2017 and March 2020 and involved participants from the Mayo Clinic, the University of Michigan, Johns Hopkins University and Pine Rest Christian Mental Health Services in Michigan. To qualify for the study, prospective participants were required to be between the ages of 18 and 65 years old and diagnosed with major depressive disorder or bipolar I or II disorder. Participants also were required to have a history of treatment resistance to traditional antidepressant therapies.
Participants who were selected for the research continued taking their existing medications throughout the trial. Researchers monitored the participants using diagnostic tests to assess factors such as depressive symptoms and suicidal ideation.
The study participants received a total of three ketamine infusions over 11 days. Each infusion was administered over 40 to 100 minutes, depending on individual responses and concerns for potential side effects. Researchers closely monitored cardiac activity and side effects during treatment.
Half of Study Participants Achieved Remission
About half (52%) of study participants achieved remission as determined by a marked reduction in their scores on the diagnostic tests. Researchers noted that the rate of remission was significant given the participants’ history of treatment resistance.
Participants also showed a marked reduction in suicidal ideation. At the onset of the study, 81% of participants had notable suicidal ideation. Following the ketamine treatment, two-thirds of participants showed a reduction in suicidality of at least 50% as measured by the diagnostic tools.
“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,” said Parikh. 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.”
During or after the infusion treatments, some participants experienced notable side effects, which were monitored using the Ketamine Side Effects Scale. Most side effects, however, had largely subsided after 60 minutes. Researchers recorded only one serious adverse event, an episode 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.”
The researchers noted the limitations of the study, including the lack of a control group that would have allowed for comparison to a placebo or alternative treatment.
“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.”
