Ketamine Assisted Psychotherapy vs. IV Ketamine Infusions: Understanding Your Treatment Options

Living with depression can feel exhausting. Some people come to ketamine treatment after trying several medications, months of therapy, or years of doing everything they were “supposed” to do yet still feeling stuck. If you’ve been researching alternatives, you may have come across the term Ketamine-Assisted Psychotherapy (KAP) and wondered what it means and how it compares to IV ketamine infusions delivered in a medical clinic.

It’s completely natural to feel uncertain. Information available online is often overwhelming, and the word “ketamine” can bring up questions about safety, legitimacy, and whether this care is right for you. At Ember Health, our goal is to offer clear, calm, and honest guidance, grounded in evidence and shaped by individual needs.

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What is Ketamine-Assisted Psychotherapy (KAP)?

The term Ketamine-Assisted Psychotherapy (KAP) has become common, but definitions vary widely. Psychology Today uses a broad definition: “utilizing ketamine to help patients struggling to find relief from mental health symptoms.” Under this umbrella, many different models exist, ranging by the mental health issue area in focus, route of administration and clinical oversight, and how psychotherapy is integrated.

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How we practice "KAP" at Ember

At Ember Health, we consider our model a form of KAP, with specific, evidence-aligned choices that emphasize medical safety, clinician supervision, and collaboration with an ongoing therapist.

Issue area in focus: Depression

While there is promising research looking at ketamine for a range of mental health conditions, about 90% of the research on ketamine relates to major depressive disorder (MDD) and depressive episodes of bipolar disorder. Ember therefore specifically focuses on treating depression with close consideration of this evidence base, and does not position ketamine as a broad substitute for comprehensive psychiatric care (Yavi et al. 2022).

Route of administration: IV ketamine delivered 1:1 by clinicians

Ketamine can be administered in several ways, via intravenous (IV), intranasal (esketamine), oral, or sublingual. Among these, IV ketamine offers the greatest safety, efficacy, and precision, allowing clinicians to control dosing moment-to-moment and provide continuous onsite monitoring. This level of oversight matters for both safety and dose optimization, especially for individuals with treatment-resistant depression.

At Ember Health, we only administer ketamine intravenously (IV). This is for two reasons: First, 87% of all studies on ketamine to date have been conducted using IV ketamine (Peyrovian et al 2020). Second, those studies have shown that IV ketamine has the highest efficacy rate among all routes of administration for addressing depression; with markedly better outcomes than oral lozenge (troche), intranasal, intramuscular, or sub-cutaneous injection.

Data supports that IV ketamine helps 75% people with treatment resistant depression (TRD) (Kryst et al. 2020) whereas intranasal helps around 40% (Lapidus et al 2015), oral helps 30% (Meshkat et al 2023), and intramuscular helps around 50% (Andrade, 2017).

Perhaps most importantly, only IV ketamine has long term outcome data supporting its use over time (Conley et al. 2021).

Why IV ketamine works best remains unclear. The current theory is that IV ketamine provides the most consistent blood/brain plasma ketamine levels during administration, and by delivering it this way, clinicians can prevent the body from breaking ketamine down before it gets to where it is needed (Glue et al. 2020).

Unlike KAP models that rely on oral or intranasal ketamine administered in non-medical settings, Ember provides IV ketamine within a specific evidence-supported dosage window, delivered exclusively by emergency-medicine–trained physicians. This setting ensures that therapists do not bear the risk of a rare but serious adverse event, should the patient react negatively to the medicine.

Timing of therapy: Before and after treatment, not during

At Ember Health, our treatment care model integrates medical safety, psychological support, and close coordination with a patient’s existing care team. 

While we do not provide or allow for therapy during sessions, we’ve structured in-office infusion care to ensure both clinical and psychological safety and support. Our in-office infusions include:

Intention-setting in a calming preparatory environment
Before each infusion, clinicians work with you and your therapist (if applicable) to set intentions and tailor the environment (music, brief breathing or grounding practices, calming cues).

IV infusion with 1:1 medical monitoring
Every infusion includes: board-certified emergency medicine physician oversight, a dedicated clinician present for the full visit, and continuous monitoring of vitals (blood pressure, oxygenation, heart rate). This 1:1 monitoring ensures safety and allows dose adjustments during the visit. 

Supportive recovery and holding of space post infusion
After infusion, Ember clinicians remain with patients until the acute effects resolve and the patient is medically stable. This ensures supervision for transient dissociation or cardiovascular effects and provides a calm, reassuring recovery environment.

We then strongly recommend that patients engage in therapy between sessions in the hours and days following infusion treatment care (not during the acute dissociative state), as evidence suggests post-infusion therapy during the neuroplastic window may extend and consolidate benefits (Kopelman et al. 2023). Ember provides training and resources for collaborating therapists so they can support patients optimally during the 24–72-hour window after infusion.

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Alternative KAP Models of Care

Many KAP offerings differ from Ember Health’s practices in important ways.

Issue areas in focus: ranges widely

Some models of KAP broaden indications beyond depression (for trauma, anxiety, existential distress, or growth-oriented work). With that said, the strongest and most consistent trial evidence remains concentrated in depression and the depressive state of bi-polar disorder (Yavi et al. 2022). There is growing evidence for ketamine’s efficacy among those living with OCD, substance use disorder, PTSD and complex trauma, and eating disorders. While ketamine has not been shown to be harmful for other mental health issue areas, there is not yet enough evidence to perform evidence-based care with clear protocols that lead to evidence-supported outcomes for these diagnoses when a person does not also have a co-diagnosis of depression.

Route of administration: Usually oral, less safe and efficacious

Many ketamine-assisted psychotherapy (KAP) programs administer ketamine orally or sublingually, usually as lozenges or tablets, which are often compounded formulations rather than the FDA-approved products used by Ember Health and other IV infusion centers. Oral ketamine has variable absorption, slower onset, and less predictable dosing compared with IV administration. Research reflects this variability: published response rates for oral ketamine in treatment-resistant depression (TRD) are modest, with approximately 30% of patients showing significant improvement. Intranasal ketamine shows somewhat higher efficacy, with response rates around 40%, but still falls short of IV ketamine.

At Ember Health, we provide IV ketamine within a defined dosage window, based on data showing response rates of 75% in TRD. IV administration allows for more rapid, reliable, and clinically predictable antidepressant effects, supporting safer and more effective treatment planning. The evidence base for oral ketamine is still developing and largely consists of small randomized trials, case series, and heterogeneous dosing protocols, which contributes to the wide variability in outcomes.

A 2025 randomized controlled trial and meta-analysis published in Journal of Affective Disorders (Silberbauer et al., 2025) evaluated oral ketamine for major depressive disorder (MDD) and bipolar depression. In the clinical trial of 45 patients, oral ketamine did not meet its primary endpoint at one week, although early improvements favored ketamine, with a number-needed-to-treat (NNT) of 4.6. A larger meta-analysis including 592 patients found that oral ketamine could be effective, with an NNT of 4.89 for response and 9.16 for remission. These findings suggest that oral ketamine can be effective, but the evidence is still limited and more variable compared with IV ketamine.

By contrast, IV ketamine has the strongest and most consistent evidence, supported by multiple controlled trials and large real-world datasets demonstrating rapid, robust, and reliable antidepressant effects. IV administration bypasses the digestive system, achieves predictable blood levels, and generally produces higher and more consistent response rates than oral ketamine, even though the 2025 meta-analysis focused on oral formulations.

Overall, oral ketamine shows meaningful potential but is less predictable and less well-studied. It also bears potential for abuse, given that it is frequently dispensed to the patient to self-dose by telehealth providers. IV ketamine remains the preferred route for treatment-resistant depression, offering greater dose control, pharmacokinetic reliability, and clinical support.

Timing of therapy: During the altered state

Some KAP programs include psychotherapy during the altered state, despite the lack of evidence for benefit from that model of care. At Ember Health, we emphasise intention‑setting and preparation before infusions, followed by structured integration therapy within 24‑72 hours after the infusion, to take advantage of the neuroplastic changes ketamine appears to induce. Human imaging studies show grey‑matter and connectivity changes within hours after infusion, suggesting a biological window when therapy may be more effective (Duek et al. 2023); (Kopelman et al. 2023). . (Moore et al, 2025)

In many KAP protocols, a therapist remains in the room throughout the acute ketamine experience. While case reports and program descriptions suggest potential clinical benefit, the scientific evidence is limited. Most studies are small, uncontrolled, or use different methods, and no large randomized trials have shown that psychotherapy delivered during the altered state is more effective than therapy conducted before or after ketamine administration.

Evidence for therapy delivered during the acute, dissociative state is limited; without clear published evidence for incremental benefit over IV ketamine by itself. Most importantly, high‑quality, randomized trials directly comparing “during” versus “after” therapy haven't been conducted. We hope that more studies on this combination will be published over time, and are eagerly awaiting any new information that could improve the quality of care we provide. 

Therefore, claims that in-session psychotherapy during ketamine infusions is superior should be considered cautiously. Current research supports structured preparation and post-infusion integration as the most evidence-informed approach (Drozdz et al. 2022).

Further, from a clinical safety standpoint, therapists often do not have the clinical experience, licensure, or training to ensure the safe administration of ketamine. While dangerous side effects of ketamine consumption are rare, they are not zero. To ensure safety, the FDA states that all ketamine administration should be monitored by a clinician with the proper clinical skills to intervene in the unlikely event of a blocked airway or heart rate spike.

Patients often tell us that therapy sessions scheduled 24 – 72 hours after an infusion feels like the right time frame to explore important topics that surfaced during the sessions with a trusted mental health professional. This also aligns with when the brain starts to be most highly neuroplastic following care. Most studies related to the benefit of structured therapy following IV ketamine care that have shown measurable benefit have been conducted in this time frame.

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Other Considerations

Safety & FDA guidance on compounded/oral ketamine

Ketamine is generally safe when administered appropriately, but it is not without risk. A key concern with many alternative ketamine-assisted psychotherapy (KAP) programs is that providers may not have the medical training to manage potential complications. This creates risk not only for patients, but also for providers and their professional licensure.

The FDA explicitly states that ketamine should only be used under the supervision of a licensed medical provider in a medical setting. The agency has also warned against the use of compounded ketamine, which includes essentially all oral forms. Because KAP typically involves oral ketamine administered with a therapist during the altered state, it does not meet FDA requirements for safe medical care.

In short, while oral KAP may be marketed as a therapeutic option, it carries significant safety and regulatory considerations that patients and providers should understand before pursuing treatment.

Efficacy Differences

• IV ketamine has been shown to be approximately 75% effective in reducing depressive symptoms in treatment-resistant depression (Silberbauer et al., 2025).
• Oral ketamine, in contrast, demonstrates a response rate of around 20%, reflecting variable absorption, slower onset, and less predictable dosing.
• Patients and provider partners should be aware of these differences in efficacy when evaluating which treatment route may be appropriate.
  
  

Data and Research Considerations

• IV ketamine has been well studied over decades, with multiple randomized controlled trials, large real-world datasets, and long-term follow-up supporting both safety and antidepressant effectiveness.
• Oral ketamine has far fewer studies, and the evidence base is limited to small trials, case series, and heterogeneous dosing protocols.
• Regarding therapy timing, there is no substantive research showing that psychotherapy during the altered ketamine state is more effective than therapy integrated before or after IV ketamine infusions. Alternatively, structured integration sessions after IV ketamine have been shown to help extend the benefits of care, supporting the collaborative model used at Ember.

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Comparing Models

Ember’s IV Ketamine + Collaborative Care

• Issue area in focus: Depression (MDD, bipolar depression), within Ember’s evidence-based scope
• Route of administration: IV ketamine in-clinic with real-time medical monitoring
• Efficacy for depression: 75%
• Therapy timing: Preparation + structured integration sessions (typically 24–72 hours post-infusion)
• Provider types: Emergency-medicine physicians and trained clinical staff; coordination with therapists for integrated care
• Monitoring & safety: Continuous 1:1 medical monitoring and EM oversight; structured protocols
• Evidence base: Extensive literature on IV ketamine for depression, including decades of clinical trials and real-world studies; response rates frequently reported as 75% for treatment-resistant depression (Schwartz et al. 2016).
• Typical cost (per treatment): ~$550 per infusion (therapy billed separately). Because infusions are typically spaced every 4–6 weeks, the overall treatment course can be more cost-efficient over time compared with frequent oral dosing.

Typical Oral KAP Model

• Issue area in focus: Varies (depression, trauma, anxiety, personal growth)
• Route of administration: Oral / sublingual lozenges (often compounded; FDA approval may be lacking)
• Efficacy for depression: 20–30%
• Therapy timing: Often includes therapy during the altered state, though timing and integration vary widely
• Provider types: Therapists and prescribers; medical oversight varies and may be limited
• Monitoring & safety: Often limited; variable medical backup and safety protocols
• Evidence base: Smaller, heterogeneous literature; case series and small trials suggest benefit, but randomized controlled evidence is limited (Al Shirawi et al., 2017). KAP is not clinically safe or advisable by the FDA, nor does it have supportive data.
• Typical cost (per treatment): ~$500–$1,200+ per session; oral ketamine often requires weekly dosing to maintain effects in the ~20% of patients who respond, which can make cumulative costs substantially higher over time.

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The “False Choice” Between KAP and IV Ketamine

Some patients feel pressured to pick one model as exclusively “right.” At Ember, we consider this a false choice: our IV infusions are delivered within a KAP-informed model (intentional preparation, in-clinic psychological support, and structured integration with a patient’s existing therapist). We emphasize evidence-aligned practice, medical safety, and collaboration with psychiatrists and therapists rather than presenting KAP as a standalone, unregulated alternative.

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Which Model Is Right for You? 

Choosing a ketamine provider is a significant decision and should be made with your therapist, psychiatrist, or primary care clinician. Together, we recommend considering the following questions before making decisions about how to proceed:

• What condition are you treating? Evidence is strongest for major depression and depressive episodes in bipolar disorder (Yavi et al. 2016). 
• What is the route of administration? IV (in-clinic) offers the greatest efficacy for treating depression (75%) vs. intranasal (esketamine, REMS required for Spravato) at 30%-40% vs. oral (often compounded) 20-30%. Ask how dosing is determined, who monitors vitals, and whether clinicians are trained to manage dissociation and cardiovascular changes. 
• How is psychotherapy integrated? If you prioritize therapy during the altered state, ask about the evidence the provider uses to support that approach and how medical safety is ensured. If you prefer therapy focused on integration after biologic treatment, ask how the provider coordinates with outside therapists and supports the post-infusion neuroplastic window (Kopelman et al. 2023). 
• Who is present during the altered state and what are their medical credentials? We advise that you ensure that a knowledgeable clinician with advanced airway management is present at all times to ensure both clinical and psychological safety. 
• What are the safety protocols and emergency procedures? Is there a plan for unexpected psychiatric reactions?
• What is the cost and dosing scheduling? What is the full, out-of-pocket cost (including therapist fees)? How often will dosing be necessary for your chosen protocol? Consider long-term cumulative costs and insurance reimbursement options.
  
  

Disclaimer 

This information is for educational purposes and does not replace medical advice. IV ketamine for depression is an off-label use of an FDA-approved medication. Ember Health requires patients to work with a licensed mental health provider. Treatment outcomes vary by individual, though 84% of our patients experience meaningful relief. All treatments are administered in medically supervised settings with 1:1 patient-to-clinician ratios.

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