A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings

This retrospective analysis (n=537) assessed the effectiveness of intravenous ketamine therapy in community-based practices i.e real-world care settings. Over half of the participants showed a response at 14-31 days post-infusion and 28.9% remitted while 73% exhibited a reduction in suicidal ideation. However, remission status was weakly inversely correlated with depression severity.

Abstract

“Background: Outcomes of ketamine intravenous therapy (KIT) for depression in real-world care settings have been minimally evaluated. We set out to quantify treatment response to KIT in a large sample of patients from community-based practices.

Methods: We retrospectively analyzed 9016 depression patients who received KIT between 2016 and 2020 at one of 178 community practices across the United States. Depression symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). The induction phase of KIT was defined to be a series of 4–8 infusions administered over 7 to 28 days.

Results: Among the 537 patients who underwent induction and had sufficient data, 53.6% of patients showed a response (≥ 50% reduction in PHQ-9 score) at 14–31 days post-induction and 28.9% remitted (PHQ-9 score drop to < 5). The effect size was d = 1.5. Among patients with baseline suicidal ideation (SI), 73.0% exhibited a reduction in SI. A subset (8.4%) of patients experienced an increase in depressive symptoms after induction while 6.0% of patients reported increased SI. The response rate was uniform across 4 levels of baseline depression severity. However, more severe illness was weakly correlated with a greater drop in scores while remission status was weakly inversely correlated with depression severity. Kaplan-Meier analyses showed that a patient who responds to KIT induction has approximately 80% probability of sustaining response at 4 weeks and approximately 60% probability at 8 weeks, even without maintenance infusions.

Conclusion: KIT can elicit a robust antidepressant response in community clinics; however, a small percentage of patients worsened.”

Authors: L. Alison McInnes, Jimmy J. Qian, Rishab S. Gargeya, Charles DeBattista & Borris Heifets

Notes

Given the legal status surrounding ketamine, it is widely available as an ‘off-label’ treatment for a range of mental health disorders. As a result, numerous clinics exist across the globe offering ketamine-assisted therapy for the treatment of mental disorders like depression and anxiety. While many clinical trials have taken place to prove the effectiveness of using ketamine to treat the aforementioned disorders, little attention has been paid to how these clinical research findings have translated into real-world practices.

The present study sought to address this research gap by analysing the data from depressed patients who received ketamine-infusion therapy (KIT) at community-based practices in the U.S. from 2016-2020. Care providers used the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms. Patients received 4-8 ketamine infusions over 7 to 28 days.

The real-world findings:

• 537 patients who had undergone induction had sufficient data and were included in the final analysis.
• 53.6% of these patients showed a response (≥ 50% reduction in PHQ-9 score) at 14–31 days post-induction and 28.9% remitted (PHQ-9 score drop to < 5) (115/537 patients remitted).
• The overall effect size was large as measured using Cohen’s d, yielding an effect size of 1.5 (d=1.5).
• Among the patients with suicidal ideation (SI), 73% had a reduction in SI.
• Negative effects inlcuded a subset (8.4%) of patients experienced an increase in depressive symptoms after induction while 6.0% of patients reported increased SI.

The present study is the largest published analysis to date that examines the effectiveness of a standard KIT induction protocol in depressed patients treated at community clinics across the U.S i.e a real-world setting. The findings of the study are roughly in line with that of previously reported results in the clinical setting. The authors do acknowledge some limitations to their findings. For example, unblinded clinicians who want to see their patients improve as well as the patients themselves who paid for KIT expecting positive outcomes may have positively skewed results. Furthermore, it was not assessed if patients were ketamine naive.

Overall, the present paper is one of the first to address the effectiveness of ketamine-assisted therapy in a real-world setting. As other psychedelic-assisted therapies become available, similar studies will be needed to assess how treatment protocols designed in the clinical setting can translate into real-world practices. In an ideal world, these protocols and therapies should directly translate into therapeutic outcomes observed during research. Therefore, studies will be needed to determine if this is true.