A recent study found that ketamine infusion therapy was associated with a significant reduction in self-reported symptoms of anxiety, depression, and suicidality, with stable effects observed during the maintenance phase. The study, published in the Journal of Affective Disorders, provides valuable insights into the real-world effectiveness of ketamine therapy, providing evidence that it can lead to significant and lasting improvements in symptoms.
Ketamine intravenous therapy is a treatment for depression that involves administering ketamine through an intravenous drip. It has been shown to be a fast and effective treatment for depression. Studies have found that a single infusion of ketamine can rapidly reduce depressive symptoms in 50-70% of patients, but most patients relapse within two weeks.
Ketamine clinics have opened across the United States, offering various infusion regimens. A recent analysis of real-world outpatients treated at one hospital suggested that repeated ketamine therapy was associated with improvement in about 20% of patients. However, detailed data on the effectiveness of ketamine intravenous therapy in real-world settings is limited. This study aimed to measure the impact of ketamine intravenous therapy on both depression and anxiety symptoms.
“I am interested in this topic because as ketamine intravenous therapy has not been FDA approved for depression, there have been few randomized controlled trials to assess the efficacy and safety of this treatment,” said study author Alison McInnes, the Vice President of Scientific Affairs at Osmind. “Therefore, it is essential that we generate real-world evidence from patients treated with ketamine intravenous therapy in community settings to convince insurers that the treatment is effective and should be covered.”
To conduct the study, the researchers gathered data from 2,758 patients who received ketamine intravenous therapy at ten locations across the United States. The patients were treated between August 2017 and March 2020, and the data was collected from electronic health records. The researchers collected demographic information such as age and sex, as well as clinical diagnoses and outcome measures including the Generalized Anxiety Disorder 7-item (GAD-7) and Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) scales.
However, approximately 40% of patients dropped out before completing the minimum required number of infusions, which means that the reported effectiveness of ketamine therapy may be overstated. To address this issue, the researchers analyzed data from two independent datasets: one included patients who were evaluated for ketamine therapy but did not receive it, and the other included patients treated with conventional antidepressants.
By comparing the results with these control groups, the researchers aimed to determine if ketamine intravenous therapy provided superior treatment effects.
During the induction phase, which involved 4-8 infusions over 28 days, the researchers found that ketamine intravenous therapy led to a significant reduction in depression and anxiety symptoms. The mean QIDS score decreased from 18.0 at baseline to 9.6 post-induction, representing a change from severe to mild depression. Similarly, the mean GAD-7 score decreased from 15.2 to 8.6 post-induction.
A significant proportion of patients responded to treatment, with 49.2% responding for depression and 47.5% responding for anxiety. The reduction in symptoms was statistically and clinically significant.
In comparison to the control groups, the ketamine intravenous therapy group had a significantly greater reduction in depression symptoms and was less likely to have worsened symptoms at follow-up. The results also showed that ketamine intravenous therapy had a greater reduction in depression symptoms compared to standard antidepressant monotherapy at every follow-up time point.
“Ketamine intravenous therapy has a robust effect size for treatment resistant depression and for anxiety. The majority of patients seeking ketamine intravenous therapy in this dataset had suicidal ideation and after an initial course of treatment over two weeks, 70% of these patients experienced improvement and 50% had no more suicidal ideation. Patient response to ketamine intravenous therapy was stable over months of follow up maintenance treatment.”
The new findings are in line with a previous study in which the researchers analyzed data from 9,016 patients who received ketamine intravenous therapy. They found that most clinicians followed similar treatment regimens, including an initial induction phase with 4-8 ketamine infusions over 2-4 weeks, followed by maintenance infusions at varying intervals.
“We were not so much surprised as gratified to identify a population of late responders who achieved a response after infusions 10-12 rather than after the traditional 6 infusion induction. This finding replicated a previous real-world study by Oliver et al. 2022 and it means that ketamine intravenous therapy needs to be personalized to individual patients. ”
“It is really fantastic to be able to replicate other studies as it makes the data even more convincing. At Osmind we are working to discover the clinical characteristics that could predict which patients will need more infusions than the standard 6 infusion induction protocol.”
The new study has some limitations. The researchers used strict inclusion and exclusion criteria, resulting in a smaller sample size that may lead to overestimating response and remission rates. Data missingness, a common issue in real-world studies on ketamine therapy, also limits the ability to assess the reasons for patient dropouts. It is unclear whether patients dropped out due to side effects during the induction phase or a perceived lack of efficacy in the maintenance phase.
“Some caveats are that we did not have safety data including dosing and side-effects. There is still concern from some members of academia that ketamine intravenous therapy administration may lead to tolerance and dependence. Osmind plans to address this in a future study. This type of data is important for patient safety and for payers who need to fully understand the potential risks of treatment.”
“At Osmind, we make an EHR designed to capture structured clinical and outcomes data on real-world patients. As such we are able to generate important research projects such as the ones we have discussed and permit clinicians to practice evidence generating medicine.”
The study, “The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis“, was authored by Tuuli M. Hietamies, L. Alison McInnes, Andrew J. Klise, Matthew J. Worley, Jimmy J. Qian, Leanne M. Williams, Boris D. Heifets, and Steven P. Levine.