Summary: A new multi-site study of 74 participants shows strong potential for intravenous (IV) ketamine to rapidly relieve severe depression and bipolar disorder that have not responded to standard treatments.
The Bio-K study found that after three IV ketamine infusions delivered over 11 days, 52% of participants reached remission. Among those who had frequent suicidal thoughts at baseline, half experienced a substantial reduction in suicidal ideation. These results reinforce ketamine’s role as a fast-acting option for some of the most treatment-resistant and high-risk psychiatric patients.
By combining clinical outcomes with blood-based molecular analyses, the study also seeks biomarkers that could predict who will benefit from ketamine, paving the way for more personalized treatment strategies.
Key Facts:
- The Bio-K study reported that 52% of severely ill patients with treatment-resistant depression or bipolar disorder reached remission after three IV ketamine infusions.
- Among participants who often had suicidal thoughts, approximately half experienced a marked decrease in suicidal ideation after treatment.
- The study is collecting biological data to identify biomarkers that may predict individual response to ketamine, supporting more tailored care for severe mood disorders.
Source: University of Michigan
Introduction
Once an anesthetic used largely in surgical settings, ketamine has transitioned in recent years into a promising option for people with severe, treatment-resistant depression and bipolar disorder. IV ketamine clinics have proliferated, and a related nasal spray formulation has gained attention as another clinically available approach. Despite growing use, clinicians and patients still face critical questions about who benefits most, why responses vary so widely, and how different delivery methods compare in effectiveness, safety, access and cost.
The Bio-K study adds meaningful evidence about IV ketamine’s potential to produce rapid, substantial improvements for people with severe mood disorders who have not improved after multiple prior treatments, including many patients who reported frequent suicidal thoughts.
Bio-K enrolled 74 participants across four clinics in Michigan, Maryland and Minnesota. After three infusions over an 11-day period, 52% of participants met remission criteria on a standard depression scale; an additional 15% achieved a partial response. Notably, among participants reporting significant suicidality at baseline, about two-thirds had at least a 50% reduction in suicidal ideation.
Who responds and why?
Not everyone benefits: roughly one-third of participants did not respond by the end of the three-infusion course. Identifying differences between responders and non-responders is central to Bio-K’s goals. The research team conducted in-depth interviews with non-responders and is analyzing blood samples to find molecular signals—such as inflammatory markers, cell signaling proteins and measures of mitochondrial metabolism—that might predict who will benefit from ketamine.
Early clinical patterns also proved informative. An early response after the first infusion was a strong predictor of later remission: two-thirds of those who improved after infusion one went on to reach remission after three infusions. Conversely, participants who showed no measurable response after two infusions were unlikely to respond to a third.
From research to clinic
The positive clinical outcomes from Bio-K contributed to the establishment of an IV ketamine clinic at University of Michigan Health. That program accepts referrals for patients with treatment-resistant depression who have already tried multiple medications. Patients typically attend several infusion visits over a month and are monitored by a multidisciplinary team including psychiatrists and anesthesiologists. The investigators have also prepared guidance to help other medical centers develop comparable programs.
Coverage and cost considerations
Insurance coverage for IV ketamine varies. Some insurers cover part of the treatment, while many patients pay out-of-pocket or rely on hospital financial assistance programs. The IV form of ketamine lacks a specific FDA approval for depression—because the generic drug is no longer patent-protected—so coverage policies differ across payers and public programs. In parallel, commercial clinics charging substantial fees for infusions have grown, though such costs place treatment out of reach for many patients. Public systems like the Veterans Health Administration are beginning to expand access for eligible veterans, reporting encouraging outcomes in early programs.
Esketamine nasal spray and comparisons
A commercial nasal spray formulation (esketamine) received FDA approval for treatment-resistant depression and has been used under careful monitoring. Unlike generic IV ketamine, esketamine is a patented formulation that went through company-sponsored trials to secure regulatory approval. University of Michigan investigators were involved in early esketamine research and plan to offer both IV ketamine and the nasal spray in clinical settings where appropriate.
Direct comparisons between IV ketamine and esketamine in routine practice remain limited. A new randomized comparative study funded by the Patient-Centered Outcomes Research Institute will enroll up to 400 people across multiple sites to compare IV versus nasal spray treatment for several weeks, with longer follow-up. That head-to-head evidence should better inform clinicians, patients and payers about relative benefits, risks and cost-effectiveness.
More about the Bio-K results
Bio-K was a collaborative effort including University of Michigan, Johns Hopkins, the Mayo Clinic and Pine Rest Christian Mental Health Services. The trial accepted participants with significant suicidality (a group often excluded from antidepressant trials) but excluded individuals with active substance use disorders, current cannabis use, schizophrenia or psychosis. Enrolled participants had failed at least two adequate medication trials or multiple sessions of electroconvulsive therapy (ECT).
The study compared different infusion durations—short (40 minutes), long (100 minutes), or a mix—and found similar safety and efficacy across those approaches. On average, participants’ depression scores on the MADRS scale fell from 28 at baseline to 11 twenty-four hours after the third infusion. By study definitions, 67% met the threshold for response (≥50% reduction), and 52% reached remission (MADRS ≤10).
About this psychopharmacology research news
Author: Kara Gavin
Source: University of Michigan
Contact: Kara Gavin – University of Michigan
Image: The image is credited to Neuroscience News
Original Research: Open access. “Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression” by Sagar Parikh et al., Journal of Affective Disorders.
Abstract
Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression
Objective
Bio-K was an open-label clinical trial testing three IV ketamine infusions for treatment-resistant unipolar and bipolar depression, with the dual aim of documenting clinical outcomes and identifying blood-based biomarkers associated with remission.
Methods
Across four U.S. sites, 75 patients aged 18–65 with refractory depression received three IV ketamine infusions over 11 days. Key exclusions included psychotic symptoms, significant substance use disorders, active cannabis use, and unstable medical conditions. Ongoing antidepressant medications were continued. Primary outcome measured remission on the Montgomery-Asberg Depression Rating Scale (MADRS); secondary outcomes included reductions in suicidal ideation. The study also compared different infusion durations and monitored safety closely.
Results
After three infusions, 52% of participants achieved remission (MADRS ≤10) and 67% met response criteria (≥50% reduction). Early improvement after the first infusion predicted later remission: 66% of those who responded after one infusion reached remission by infusion three, while only 20% of participants who had not responded after two infusions achieved remission later. Most participants (81%) reported significant suicidal ideation at baseline; two-thirds of these experienced at least a 50% reduction in suicidality. Side effects were generally minimal, and infusion duration (40 vs. 100 minutes) did not materially affect outcomes.
Conclusions
The Bio-K clinical outcomes across multiple sites demonstrate notable acute efficacy and tolerability of IV ketamine for severe, treatment-refractory depressive episodes. Early clinical response appears predictive of eventual remission. While the open-label design limits causal conclusions, these real-world findings support further investigation and ongoing biomarker analyses to guide individualized treatment strategies.