The Benefits of Ketamine Therapy for Treatment Resistant Depression
If you’ve been dealing with depression that just won’t lift, despite trying medication, therapy, or making healthy lifestyle changes, you’re definitely not the only one. And more importantly, there are other options. One that’s gaining traction is ketamine therapy, a fast-acting treatment that’s offering real hope to people who feel like they’ve tried everything else.
Originally developed as an anesthetic, ketamine has found a new role in mental health treatment, and for good reason: it works quickly. Unlike traditional antidepressants, which can take weeks or even months to show results, ketamine can ease symptoms within hours. For someone stuck in a long cycle of hopelessness, that kind of speed can make a huge difference.
In this guide, we’ll walk you through what ketamine therapy is, how it works, and why it’s helping so many people.
What Is Ketamine Therapy?
Let’s start with the basics.
Ketamine was first used in hospitals to help patients stay asleep during surgery. These days, in much smaller doses and under medical supervision, it’s being used in a very different way to help people with treatment-resistant depression (TRD).
So, what makes ketamine different? Instead of focusing on brain chemicals like serotonin or dopamine (like most antidepressants), ketamine works with a different chemical called glutamate. Glutamate is involved in how we think, feel, and adapt and plays a big role in mood regulation.
There are two primary forms used in therapy:
Generic ketamine (usually delivered through an IV or lozenge)
Spravato (a nasal spray version of esketamine, which is closely related)
Spravato is FDA-approved for treating depression and is only given under a doctor’s supervision in a clinic.
How Does Ketamine Therapy Work?
Ketamine helps the brain “reset” by boosting glutamate and encouraging it to form new, healthier connections. In people with depression, parts of the brain can get stuck in patterns that make it hard to feel joy or motivation. Ketamine helps break that cycle, often in just hours or days.
Depending on the form, treatment may involve a nasal spray (Spravato), IV infusion, or lozenge. It’s always done in a medical setting, with a trained provider monitoring the process.
What Is Treatment-Resistant Depression (TRD)?
We all go through challenging seasons in life, but TRD is different.
Treatment-resistant depression refers to a condition in which symptoms persist despite trying at least two different antidepressant medications at adequate doses and durations, often alongside therapy or lifestyle modifications, without achieving significant relief.
It can show up as:
Feeling emotionally flat or persistently down
Low energy or trouble focusing, even with treatment.
Suicidal thoughts that don’t ease up
A sense that nothing is working, even though you’re trying
Roughly 1 in 3 people with depression experience TRD. It’s frustrating, discouraging, and draining, but it can be treated.
So, Why Is It Called “Resistant”?
TRD means:
You’ve tried at least two antidepressants
At proper doses, for 6–8 weeks or more
And your symptoms didn’t improve, or only got slightly better
Even though you’ve taken the proper steps, medication, therapy, and lifestyle changes, the depression is still showing up and making life more complex than it needs to be. That doesn’t mean you’ve failed; it means your journey might require a different path forward, and there is still hope for relief and healing.
Signs You May Have TRD
If you’re wondering whether you or someone close to you might be dealing with TRD, here are a few clues:
You’ve tried multiple antidepressants without real improvement
You still feel down, numb, or disconnected.
You struggle with low energy and can’t focus on or enjoy things in ways you used to.
Suicidal thoughts haven’t gone away, even with therapy or medications.
Why Does TRD Happen?
There’s no single reason, but here are a few possible contributors:
Genetics: Everyone responds to medication differently, and genetics can play a significant role. Some people may have genetic differences that affect how their body absorbs, processes, or responds to antidepressants, which can make those medications less effective or even cause unwanted side effects.
Brain Chemistry: Traditional antidepressants are designed to target certain brain chemicals, like serotonin or dopamine. But in some people, depression may be linked to other pathways, such as glutamate or inflammation, making standard treatments less helpful. The brain may also struggle to form or repair connections between neurons, which affects how it responds to stress, emotions, and treatment.
Other Health Issues: TRD often exists alongside other mental health issues like anxiety, PTSD, or bipolar disorder. Physical health conditions like chronic pain, hormonal imbalances, or sleep disorders can also interfere with how well depression treatments work. When multiple conditions overlap, treating depression becomes more complex.
Trauma or Chronic Stress: Unresolved trauma, such as abuse, loss, or major life disruptions, can profoundly affect the brain and body.. Even with medication, the emotional effects of trauma or chronic stress may continue to fuel depressive symptoms. In these cases, medication alone often isn’t enough to bring about the life changing relief that we desire. full relief.
These factors make depression more complicated to treat in the usual way. But newer therapies like ketamine are opening doors for people who felt stuck.
What Can You Do?
If you think you might be dealing with TRD, don’t give up. You still have options:
Trying a different combination of medications
Exploring therapy types like CBT, DBT, or ACT
Considering innovative treatments like ketamine therapy
Looking at whole-person care, including lifestyle support
Why People Are Turning to Ketamine Therapy
As more research comes out, ketamine therapy is gaining popularity for its unique benefits, especially when other treatments haven’t worked. Here’s what makes it stand out:
1. Relief When Nothing Else Has Worked
For people with TRD, ketamine offers a new way forward when traditional antidepressants and therapies haven’t provided results. It works differently from standard medications by targeting glutamate, a brain chemical linked to mood and learning. This alternative approach gives hope to those who have spent months, or even years, trying to feel better without success.
2. Rapid Improvement in Mood
Unlike most antidepressants that take weeks to kick in, ketamine can start to ease symptoms in just hours to days. This is especially important for people stuck in deep, prolonged depressive episodes. Fast relief can break the cycle of hopelessness and help people re-engage with life and treatment. In one study, about 71% of participants showed improvement within one day, and 35% maintained the response for at least one week.
3. Reduces Suicidal Thinking
Ketamine has shown strong effects in lowering suicidal thoughts, often quickly and noticeably. This benefit is vital for those in crisis who need immediate support, especially when other medications are too slow to help. For people with TRD who often feel trapped in their depression, this quick reduction in suicidal ideation can be life-changing. In one study, a single infusion of ketamine significantly reduced suicidal thoughts in depressed patients within 24 hours.
4. Improves Brain Connectivity and Healing
Chronic depression can damage the brain’s ability to function at its best, impacting memory, focus, and emotional regulation. Ketamine helps restore these connections by encouraging the brain to build new neural pathways. Over time, this may help people with TRD feel more emotionally stable, mentally clear, and open to healing.
5. Creates Space for Long-Term Recovery
While ketamine isn’t a cure, it can create a window of relief where other treatments, like talk therapy, self-care, or lifestyle changes, become more effective. For someone with TRD, this can be the breakthrough moment they’ve needed to begin healing truly. It’s not just about feeling better temporarily, it’s about opening the door to more profound, lasting progress.
Who Might Benefit?
Ketamine therapy may help if you’re dealing with:
Treatment-resistant depression
Major depressive disorder
Suicidal thoughts
Anxiety disorders
PTSD
OCD
Bipolar depression (with supervision)
Chronic pain (e.g., fibromyalgia, CRPS)
Emotional distress in palliative care
Are There Side Effects?
Most people respond well to ketamine therapy, though it can sometimes cause brief, mild effects such as:
Dizziness or nausea
Changes in blood pressure or heart rate
Temporary confusion or disorientation
Blurred vision or lightheadedness
Fatigue or emotional sensitivity afterward
A brief feeling of being “disconnected” from your body or surroundings
Working with licensed professionals is equally important. Ketamine-assisted psychotherapy (KAP) should never be done casually or without trained supervision. At Stanford Psychological Services, your safety and emotional well-being are at the heart of what we do.
Why Choose Stanford Psychological Services?
At Stanford Psychological Services, we believe in personalized, compassionate care. Ketamine therapy isn’t one-size-fits-all, and neither is our approach. We take the time to understand your unique experience and walk with you every step of the way.
If you’re curious about whether ketamine therapy could help, we’d love to talk. You don’t have to do this alone; healing is possible, even if it hasn’t felt that way in a long time.
Let’s take that first step together.
