How Does Ketamine Therapy for Depression Work? Our Clinician Reflects on 1000+ Treatments
By Bri Bendixsen, MA, Psychotherapist and Psychedelic-Assisted Therapist
The vast majority of ketamine research looks at its use for treating depression. Although ketamine has been proven to improve symptoms of PTSD, anxiety and other conditions, it’s treatment-resistant depression (TRD) where ketamine takes center stage. Clinical studies report 60–70% positive response rates with a single dose of ketamine for depression.
Ketamine produces fast-acting antidepressant effects by acting on the brain’s glutamate system, rather than targeting serotonin or dopamine pathways. This leads to rapid changes in brain connectivity, which leads to a quick therapeutic response.
Many ask “how fast does ketamine work for depression?” Well, the most significant improvements are seen in those who receive ketamine-assisted psychotherapy (KAP) sessions versus just ketamine alone.
So, how does ketamine therapy work? In this piece, we’ll explore different ketamine treatments for depression, what to expect from the medicine experience, integration considerations, and when you know it’s the right time to consider ketamine-assisted psychotherapy.
For more general information, visit Reflective Healing’s ketamine therapy in Colorado page.
Ketamine Treatment vs. Ketamine-Assisted Psychotherapy (KAP) for Depression
You may be familiar with ketamine treatment with the boom of independent IV clinics, where clients receive ketamine intravenously over several weeks. It has shown effectiveness in individuals experiencing suicidal ideation, and has been extensively used for treatment-resistant depression. Ketamine isn't necessarily a first-option treatment for depression, but it can help when more longstanding treatments haven't been effective.
Ketamine by itself already has a pretty rapid antidepressant effect. That’s why direct-to-door deliveries of ketamine are thriving too, prized for their cheaper and more convenient model, but also dubbed “ketamine candy.” These treatments may run the risk of falling into the Western medical models again: The “take medication daily for symptoms” mentality, without psychotherapy (which is generally key for people recovering from depression).
Some clients are not open to trying therapy, but, in our practice, it’s a necessary step of treatment. Some say ketamine only improves symptoms of depression and “doesn’t offer a cure.” But a more sustainable antidepressant effect can only really occur with ongoing psychotherapy and adequate integration – but many clinics fail to provide that.
How Ketamine Therapy Supports Individuals Struggling With Depression.
Many living with depression feel a general sense of apathy about their life, and a lack of joy or connection. Ketamine has been shown to minimize these symptoms of depression quickly after ingestion. In one animal study, researchers discovered that ketamine “quickly restored the coordinated activity of prefrontal neural circuits that were disrupted by chronic stress.” Moreover, they found that ketamine helped the brain rebuild healthy neural pathways by encouraging new connections between brain cells.
They also stated that interventions aimed at “enhancing synapse formation” could more likely sustain the antidepressant effects of ketamine. Integration and psychotherapy after the sessions are likely what help to support and maintain these neurobiological changes. This includes promoting healthy habits such as consistent physical activity, balanced nutrition, and social engagement, as well as setting healthy boundaries, reassessing relationships, building work/life balance, and more.
Ketamine allows people to come back to their own inner intuition or wisdom, to discover what they want to do. Perhaps you are stuck in a job you hate or in the monotony of day-to-day life and not able to engage with anything of deeper meaning or value. Maybe you’ve abandoned a hobby that you can rediscover through new self-care practices. Ketamine can help people separate obligations and expectations from what they genuinely want for themselves. Clients are generally able to tune into a deeper sense of self-trust.
I’ve found ketamine to be particularly helpful for clients that seem to be functioning on a day-to-day basis, where their life may look good on paper, but they still feel disconnected and deeply sad.
The distinctive dissociative anesthetic effect
Ketamine’s dissociative anesthetic effect makes it unique compared to other psychedelics. The medicine provides distance between the thoughts and the emotional experiences that arise, letting them show up and pass without attachment. Usually traumatic memories appear in the medicine at some point, but clients are able to analyze them without the anger or sadness that may show up in a traditional psychotherapy session.
Instead of "I'm so angry, I'm so sad," it could look like: "Oh, I'm noticing anger about that experience" or “I’m noticing that thought hooks my attention, how does that make me feel?”
I’ve also noticed that, with ketamine, the vast majority of clients don't start looping or get stuck; it gently pulls them out of rumination. You may experience a certain memory, trauma, or thought, it may be accompanied by a realization, and, then, most likely, it will shift into something different. I often tell people ketamine is like the Colorado weather: If you don't like what's happening, just give it a minute because it's going to change. With other psychedelics, the same content may be regurgitated over and over, which can be hard for some clients to shift out of.
What To Expect From Your Therapist in Ketamine Sessions
If you’re wondering how many ketamine treatments for depression are typically needed, this is the typical KAP treatment protocol:
Generally, we start with at least three sessions of psychotherapy to build a strong client-therapist relationship. More sessions may be needed to build rapport.
In my practice, I ask people to commit to at least two KAP medicine sessions, but ideally we would follow the six-session protocol (following IV ketamine research). If clients don’t feel a connection to the medicine and they're not noticing any benefit, then there's no pressure to continue. After the sixth session (or we may choose to do eight), we have a one-month break for integration. During the medicine sessions, KAP providers generally take a back seat, offering non-directive support where necessary. We don’t bounce off questions, dig into verbal therapeutic material or intervene; your inner healing intelligence is our guide. The dialogue, questions, and reflections (characteristic of traditional therapy) are saved for integration and the psychotherapy sessions.
We continue psychotherapy weekly or bi-weekly after the KAP sequence, and continuously reassess. If relieved of some depressive burdens, people can sometimes confront past trauma, abandonment, or loss. This can be an incredibly healing process, but it can be difficult to navigate on your own. Therefore, the vast majority of clients choose to continue with psychotherapy with providers that understand the ketamine context.
Why Integration Matters in Ketamine Therapy for Depression
A possible unintended consequence of KAP therapy is something that Dr. Jessica Katzman calls the “therapeutic bends.” It is when people rapidly ascend from the depths of depression, which can look almost hypomanic – but it's not something to be pathologized. It could be a sign of someone coming into the fullness of their life expression.
However, rapid growth or depression remission can be destabilizing, not only for the clients but also for their therapists, family, and friends. People close to someone with long-term depression may struggle to adjust when improvement happens suddenly. And, unfortunately, surprised reactions from support networks can encourage clients to return to their previous baseline. That’s where integration and ongoing psychotherapy are really helpful during that period of “recovery.”
Katzman wrote in Psychedelics Today that the reactions post-KAP can range from “over-reliance on older coping styles that no longer match one’s current state, to the distress that comes from the loss of a habituated identity (‘I don’t even know who I am anymore, without my old buddy, Depression’).” Sometimes, as clients recover, they realize the damage their illness caused (e.g., lost time, broken relationships, financial strain), which can be deeply painful to process.
That’s why it’s vital that KAP providers set expectations with clients that even good change, like feeling better in yourself, can be some of life’s most stressful events.
“Though we think about depression as “sadness” and recovery as “happiness,” the reality is often not as simple. Depression can present with a numbing or flattening of emotions, and recovery may mean regaining access to a wide range of different feeling-states.” - Dr. Jessica Katzman
Do I Have To Consider Tapering Off Antidepressants?
It is not necessary to taper off antidepressants or anti-anxiety medications with ketamine, which also differentiates it from other psychedelics. Ketamine is one of the psychedelic medicines where people can continue their medication like normal.
However, adding some KAP sessions during a medication tapering process can be really helpful in reducing withdrawal side effects. Clients may choose to do so during or after the KAP sequence, depending on guidance from their prescriber.
There are certain medications that clients may need to pause the day before a KAP session, such as lamotrigine (Lamictal) and ADHD or stimulant medications. They can be resumed afterward. And benzos have been seen to blunt some of the therapeutic effects of ketamine.
Who Is a Good Candidate for Ketamine Therapy? Knowing When It’s Time to Try KAP for Depression
If you are starting to explore psychedelic medicines, that's usually the first sign that it is worth you having an initial conversation with a KAP provider. KAP is a tool in my therapeutic toolkit, but it's definitely not the only tool. Know that most KAP providers are happy to explore psychotherapy for quite some time, and try KAP at a much later date. It’s important to establish a strong relationship with a therapist before entering an altered state.
I’ve also seen clients turn to ketamine after trying multiple different medications for depression with few benefits or changes. Or perhaps they’ve been on medication for years and feel a blunted affect; they are no longer very depressed or actively suicidal but also not able to tap into the joy, awe, and highs of life.
There are some grand claims in the media about the promise of psychedelics as a “miracle cure.” I never want to oversell ketamine to anybody. Sometimes clients can have experiences that really shake up their lives, but that doesn't happen across the board. I definitely do not promise that, but I want people to know that it could happen too.
Usually, it's never anything that you don't know already, but you’ve been trying to ignore it. Perhaps something about a long-term relationship, a job you are miserable in, your sexuality. After a ketamine experience, clients should be aware that sometimes it is hard to unsee certain things. You usually can't just put the genie back in the bottle.
A ketamine experience may lead to massive life decisions and clients need to be aware of that if they think something is simmering under the surface. It’s important to set expectations for all involved that recovery may involve unearthing unanticipated feelings and memories.
If you’re looking for ketamine therapy in Colorado, our skilled KAP providers at Reflective Healing Center are ready to support you on your journey. Book a 30-minute KAP consultation with one of our therapists today.
Ketamine Therapy for Depression: FAQs
How fast does ketamine work for depression?
Many people notice improvement in mood within hours to 24 hours after a treatment, though effects can vary and build over a series of sessions. The most significant improvements are seen in those who receive ketamine-assisted psychotherapy (KAP) sessions versus just ketamine alone.
How many ketamine treatments are recommended for depression?
A common starting protocol is six sessions over six weeks, followed by maintenance sessions as needed based on client response. With ketamine-assisted psychotherapy (KAP), providers usually start with a few psychotherapy sessions to build rapport and set integration goals, followed by a series of ketamine sessions. After the initial course of about six treatments, ongoing therapy is typically recommended.
Who is a good candidate for ketamine treatment?
Ketamine is often considered for people with treatment-resistant depression or those who haven’t responded well to antidepressants or therapy. A full medical and psychological evaluation is needed to ensure it’s appropriate and safe for the individual’s situation.
How can I find a ketamine clinic near me?
The best way is to get referrals from friends or family. Another way is to search online for clinics offering ketamine-assisted psychotherapy (KAP) in your area. Be sure to read the information carefully; who’s the provider, what’s their background, where did they train, etc. And, of course, have a consultation call. Feel the person out, and make sure you feel comfortable with them as a human.
