Summary: Yes, new research shows there is a way to improve ketamine treatment for people with severe, treatment-resistant depression: it works by adding one simple step to the treatment process.
Key Points:
- Ketamine is a powerful medication currently in use off label for the treatment of severe depression and treatment resistant depression.
- A ketamine derivative, SPRAVATO®, has FDA approval and can also help patients with severe depression.
- When a person has clinical depressive disorder and does not respond to at least two attempts at treatment with psychotherapy and standard antidepressants, they have treatment-resistant depression (TRD).
- Ketamine and SPRAVATO® can help people with severe depression and TRD, with a new study showing a simple way to improve ketamine treatment for people with severe, treatment-resistant depression.
Ketamine Treatment + Positive Images: Can Adding Something Simple Improve Results?
We should start this article by ensuring we’re all on the same page, with an answer to this basic question:
What is ketamine?
Medical scientists developed ketamine in the 1960s as an anesthetic and pain reliever. Ketamine received FDA approval for medical use in humans in 1970. Interest in the used of a less powerful derivative of ketamine began around the year 2000. Currently, a derivative of ketamine called racemic ketamine – brand named SPRAVATO® – is FDA-approved for the treatment of several mental health diagnoses. Ketamine itself – in the form of intravenous infusions (IV ketamine) – is used as an off-label treatment for treatment for treatment-resistant depression (TRD), major depressive disorder (MDD) with suicidal thoughts or behaviors, bipolar depression (BD-I & BD-II), anxiety disorders (AD), post-traumatic stress disorder (PTSD, and other mental health conditions.
The importance of ketamine and SPRAVATO® is their effectiveness in helping reduce symptoms in people with treatment-resistant diagnoses quickly, with positive results that persist longer than typical antidepressants, whose effect fades when a patient stops taking the medication.
That’s significant because roughly 30 percent of people with severe depression do not experience relief from a traditional treatment approach, which involves a combination of psychotherapy and antidepressant medication.
We’ll say that again: almost a third of people who engage in treatment for depression do not experience any improvement.
In many cases, ketamine can help people with TRD. Some people report symptom relief within hours. However, some people who engage in treatment with ketamine report symptom relief fades within a month of a ketamine infusion.
A standard course of treatment with IV ketamine infusions involves six (6) ketamine infusions over 2-3 weeks, with booster infusions scheduled as needed. Some patients do not require boosters at all, while some require them monthly or every six months: the schedule depends on the patient.
That’s where this research comes in. To keep costs for patients down and extend the duration of symptom relief, they experimented with a simple idea: after a single ketamine infusion, show patients positive images paired with positive words about themselves and track the results.
Let’s see how they set up the study, and what they found.
First, we’ll take a moment to share the latest statistics on depression and treatment resistant depression in the U.S.
How Many People Have Severe Depression and/or TRD?
The 2025 National Survey on Drug Use and Health (2025 NSDUH), an annual survey with over 70,000 participant, shows the following prevalence of depression among adults 18+ in the U.S.
Major Depressive Episode (MDE) in 2025: Prevalence and Treatment
- Total: 19.7 million
- Received treatment: 12.9 million
- Received prescription medication: 10.2 million
- With severe impairment: 13.8 million
- Received treatment: 9.5 million
- Received prescription medication: 7.6 million
Based on the fact that around a third of people with depression develop TRD, those figures close to six million adults in the U.S. had TRD in 2025. Those are the people this article is for, and the group who may benefit most from any way to improve ketamine treatment for severe, treatment resistant depression.
Now – with the scope of the problem clear in our minds – let’s take a look at that study.
Ketamine, Positive Self-Image, and Symptom Relief
To conduct the study – “A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial” – researchers recruited 154 adults between the ages of 18 and 60 with a diagnosis of treatment-resistant depression (TRD). They divided the participants into three groups:
- The treatment group. This group of patients received one infusion of ketamine. The next day, they participated in an intervention called ASAT, or “automated self-association training,” which we’ll describe below.
- Control group 1. This group received ketamine and no ASAT intervention.
- Control group 2. This group received the ASAT intervention, but instead of a ketamine infusion, received a saline placebo.
Let’s talk about the ASAT intervention. Previous research showed that following a ketamine infusion, patients were capable of experiencing “rapid shifts in implicit self-association” that suggests “ketamine creates the requisite malleability in information processing” that may enable therapists “…to capitalize on this plasticity and to shift self-associations in a positive direction.”
Here’s how the ASAT intervention worked. Beginning the day after the ketamine infusion, patients received:
- Eight 15- to 20-minute sessions, delivered twice a day for 4 consecutive days
- Sessions were designed to reinforce implicit associations between positive traits and self-referential stimuli, as described above.
We’ll explain that last bullet point. During an ASAT session, participants viewed words such as “happy, sweet, attractive” alongside pictures of themselves. In addition, they viewed pictures of other happy, smiling, people, which were also paired with positive words or phrases. Note: the ASAT sessions were supervised by a clinician, but were fully automated, and can be delivered via electronic media and do not require any return, in-person visits.
Let’s take a look at the results.
Ketamine + ASAT (Automated Positive Reinforcing Words and Images)
Treatment Group:
- One day (24 hours) post-treatment: Significant symptom relief for all patients
- One month (30 days) post-treatment: Significant symptom relief persisted for the entire month
Ketamine + No ASAT:
- One day (24 hours) post-treatment: Significant symptom relief for all patients
- One month (30 days) post-treatment: Symptom relief faded to pre-treatment levels
Placebo + ASAT:
- One day (24 hours) post-treatment: Moderate symptom relief for all patients. Symptom relief was less robust than the treatment group.
- One month (30 days) post-treatment: Moderate symptom relief persisted for the entire month
We’ll discuss these results below.
A Simple Addition Improves Results
This study is relevant for several reasons.
First, it’s responsive to the current mental health environment in the U.S. We need research like this to address the increase in rates of mental health diagnoses nationwide. These increases began before the COVID-19 pandemic, were exacerbated by the pandemic, and have not decreased since. Therefore, this research meets a clear and demonstrated need in the general population.
Second, it builds on a new and innovative approach to treatment-resistant depression – IV ketamine – which evidence shows can relive the symptoms of treatment-resistant depression.
Third, it shows that a cost-effective addition to ketamine treatment – ASAT – can significantly extend the effects of ketamine symptom reduction after only one infusion. That’s an important finding, because most courses of treatment with IV ketamine involve 2-3 sessions, with additional boosters as needed. The addition of an automated component that a patient can engage in via computer – at home – may be a way to reduce costs and improve treatment efficacy at the same time. Here’s how the study authors describe the results of this research:
“The global burden of depression is extremely high and is expected to continue to increase within the current context of a significant pandemic. There is an urgent need for novel treatment approaches, particularly those that can provide relief efficiently and at scale. If the present results can be replicated, this novel, integrative treatment may provide a method to urgently bring relief and to efficiently extend this relief via safe, low-cost, portable techniques.”
What We Can Do and Where We Can Go From Here
In the U.S in 2025, experts estimate that over six million people have treatment-resistant depression. That means they’ve all developed depression, and tried treatment – at least two times with different medication – and didn’t get any better.
They’re ready for what’s next. They’re ready for a treatment that will help them reduce their symptoms and live a self-directed life
We’re ready for what’s next too. We’re ready to meet the increased mental health needs of our population in this new era. And one way we can meet that need is by staying current on the latest, most innovative ways to offer treatment and support to people who need it the most. Treatment-resistant depression, and other treatment-resistant mental health disorders, can make typical daily life almost impossible for people with severe and disruptive symptoms.
What we can do for patients is offer them the most effective, innovative treatments available. Where we go from here is forward. We can use the latest evidence-based strategies to offer symptom relief to people with treatment-resistant disorders who may have given up hope on finding relief and reclaiming their lives.
The results of the study we discuss above tell us that we now have another tool at our disposal, which we can use to help people with treatment-resistant depressive disorders start the road to recovery, when previous efforts at recovery fell short. This new treatment can offer something very important: the hope that real recovery from severe, treatment-resistant depression is possible.
Gianna Melendez
Jodie Dahl, CpHT