Ketamine is a prescription-only medicine that may be prescribed off-label by our medical team following a comprehensive assessment to assist in the psychotherapy.
Ketamine is a prescription-only medicine that may be prescribed off-label by our medical team following a comprehensive assessment to assist in the psychotherapy.
A CLINICIAN’S PERSPECTIVE
Psychiatry is in the middle of a significant rethink. The theoretical framework that has shaped the field for sixty years has brought real benefit to many people, but it has also left a substantial and well-documented gap behind.
This page explores where ketamine fits within that rethink, how it differs from conventional psychiatric treatment, and what its emergence may tell us about the future of mental healthcare.
Evidence-led
Built around current psychiatric and neuroscientific research.
Clinically relevant
Focused on what the evidence means for real-world treatment.
Regularly reviewed
Updated as the research and clinical landscape develop.
THE MONOAMINE HYPOTHESIS
The monoamine hypothesis emerged during the 1960s after researchers observed that medicines affecting serotonin, noradrenaline and dopamine could improve depression. It became an influential framework for understanding the illness and helped shape the development and use of MAOIs, tricyclic antidepressants, SSRIs and SNRIs.
These medicines have brought real relief to many people. Their immediate action increases or alters monoamine signalling, although their therapeutic effects are now understood to involve much more than simply correcting a shortage of serotonin or another neurotransmitter. Changes in receptors, stress systems, gene expression, neuroplasticity and communication between brain networks may all contribute.
The limitation of the original hypothesis is that depression cannot be explained reliably as a straightforward monoamine deficiency. In the STAR*D study, approximately 28–33% of patients achieved remission following an initial course of citalopram, while response and remission became less likely with each subsequent treatment step. More recent estimates suggest that at least 30% of people with depression may meet commonly used criteria for treatment-resistant depression.
For people who remain unwell despite appropriate treatment, the issue may not be that serotonin is irrelevant. It may be that monoamine signalling represents only one part of a far more complex illness involving stress, inflammation, learning, neural connectivity and the brain’s ability to adapt. Repeatedly adjusting the same system will not reach every process capable of sustaining depression.
A BROADER NEUROBIOLOGICAL MODEL
Ketamine’s rapid antidepressant effects forced psychiatry to look beyond traditional monoamine-based treatments. For the first time, a medicine acting primarily through the glutamate system was shown to reduce depressive symptoms within hours in some people, including patients who had not responded sufficiently to established treatments.
Glutamate is the brain’s principal excitatory neurotransmitter and plays a central role in learning, memory, communication between neurons and synaptic plasticity. Ketamine blocks NMDA receptors, initiating a more complex cascade involving glutamate release, AMPA-receptor signalling, BDNF and the strengthening or formation of synaptic connections. These processes may help explain why changes can emerge far more quickly than with conventional antidepressants.
Ketamine does not prove that depression is simply a disorder of glutamate, just as the effectiveness of SSRIs never proved that depression was simply caused by too little serotonin. Its importance lies in demonstrating that rapid improvement can arise through an entirely different biological pathway and that synaptic flexibility may be a crucial therapeutic target.
The glutamate model therefore does not need to replace the monoamine model. It broadens it. Depression is increasingly understood as a diverse group of conditions involving several interacting systems rather than one chemical imbalance with one universal solution. Ketamine has helped reveal why established antidepressants help many people, why they leave a substantial minority behind, and why a different mechanism may sometimes be needed.
Ketamine opened a door onto a broader understanding of depression — and what may still be possible when established treatments have not been enough.
COMPLEMENTARY MODELS
Ketamine-assisted psychotherapy does not replace psychiatry. It adds a different therapeutic dimension to it.
Conventional psychiatric care provides an essential framework for diagnosis, prescribing, medication review, risk management and the treatment of complex mental-health conditions. For many people, medication and established psychiatric interventions provide substantial relief.
The limitation is not that psychiatry operates only through a simplistic chemical model. It is that medication alone cannot always address the developmental experiences, relationships, beliefs and protective patterns that may continue to shape a person’s difficulties. Biological and psychological processes interact, and neither perspective fully explains every case.
KAP brings those perspectives together. Medical assessment, prescribing and monitoring provide the clinical framework. Preparation, therapeutic presence and integration help the person explore what emerges and connect the treatment experience with their history, relationships and everyday life.
As Dr Fernando Espi Forcen of McLean Hospital presented at the 2025 APA Annual Meeting: “Ketamine-assisted psychotherapy is not trying to compete with ketamine therapy. It is just trying to give patients a different option. A patient and their provider will decide which model is going to work better. These 2 models should coexist and complement each other”
Psychiatrists and psychotherapists are not addressing rival versions of the same problem. They contribute different forms of expertise. When those roles are clearly defined and properly integrated, treatment can address both clinical symptoms and the person experiencing them.
UNDERSTANDING THE DIFFERENCE
Ketamine infusion and ketamine-assisted psychotherapy both use the same medicine, but they place it within different models of care.
In an infusion clinic, ketamine is generally administered intravenously within a medical setting. The principal aim is usually symptom reduction through ketamine’s pharmacological effects, with monitoring and clinical support provided throughout treatment. This is a legitimate and evidence-based approach, particularly in treatment-resistant depression.
KAP places the medicine within a broader psychotherapeutic process. Treatment usually includes preparation beforehand, psychological support during or around the ketamine session, and integration afterwards. The intention is not only to observe whether symptoms improve, but to explore how changes in mood, perspective or psychological flexibility might be connected with longer-term therapeutic work.
Research into this combined model is encouraging, but it remains less mature than the evidence for ketamine as a medical treatment. Observational studies report improvements across several conditions, while early controlled work suggests that psychotherapy may help some people sustain or work with the response. Current research cannot yet establish precisely how much psychotherapy adds, which approaches are most effective, or which patients benefit most from the combination.
The distinction is therefore not that one model is valid and the other is incomplete. They have different aims. Infusion treatment centres primarily on ketamine’s medical effects; KAP deliberately combines those effects with an ongoing psychological process.
WHEN TO INVOLVE A PSYCHIATRIST
KAP is not a replacement for psychiatric care. Some presentations require psychiatric involvement before treatment can be considered, and continued psychiatric care throughout the programme may be essential.
People on complex medication regimes need careful assessment of interactions before treatment begins. Where a patient’s medication history is particularly complex, direct liaison with their prescribing psychiatrist is a normal and appropriate part of the process.
People with a history of psychosis or bipolar disorder require careful specialist assessment before KAP is considered. These presentations require psychiatric input — not as a procedural formality, but as clinical necessity.
People in acute psychiatric crisis need the level of care that a psychiatric service can provide. KAP is a planned, structured intervention — not an emergency treatment. The appropriate sequencing is stabilisation first, with KAP considered as a next step once acute risk has been managed.
At The Emerge Clinic, we work within the wider psychiatric and medical system, not around it. Where a specialist psychiatric intervention is indicated, we say so clearly. Where we don’t think KAP is the right next step for someone’s specific situation, we tell them that too.
WHO BENEFITS MOST FROM KAP
Although no assessment can predict an individual response, current evidence and clinical experience suggest several factors that may make KAP particularly relevant.
People who have not responded adequately to two or more antidepressant medication trials at therapeutic dose — the standard clinical definition of treatment-resistant depression — represent the clearest candidate group. People whose depression has a significant cognitive component — rumination, rigid self-critical thinking, psychological inflexibility — appear particularly likely to benefit, given ketamine’s default mode network and central executive network effects.
People whose difficulties involve deeply established emotional and relational patterns may also find the combined model relevant. Ketamine can temporarily alter perspective and psychological flexibility, while psychotherapy provides a structured way to understand and work with what emerges.
People who are ready to engage actively with the therapeutic process — not just to receive a pharmacological intervention, but to do the preparation and integration work that maximises the medicine’s benefit.
KAP is not for everyone. People with active psychosis, mania or acute psychiatric crisis require a different level of care first. People who are primarily looking for a standalone ketamine experience without the surrounding psychotherapeutic structure will find that what we offer is something different. Assessment exists precisely to answer the question of whether KAP is right for a specific person — honestly, thoroughly and without obligation.
THE FUTURE OF PSYCHIATRY AND KAP’S ROLE
Ketamine is widely regarded within psychiatry as the proof of concept for a new generation of treatments — but it is the opening move.
The success of ketamine in treatment-resistant depression has validated the glutamate hypothesis and spurred research into new-generation glutamate-targeting agents. Newer compounds are currently in clinical development, including pure R-ketamine, rapastinel, and NMDA-modulating agents. The therapeutic model developed around KAP — careful preparation, medically supervised experience, structured integration — is now being applied to emerging treatments including psilocybin and MDMA, both of which are in advanced clinical trials for depression and PTSD respectively.
What ketamine has demonstrated is that rapid neurobiological change is achievable — and that the conditions surrounding that change determine whether it translates into lasting psychological benefit. The future of psychiatry is not about replacing the medical model with a psychedelic one — it is about accurate neurobiological understanding, faster-acting interventions, and genuinely individualised care.
For someone considering KAP, the important point is this: it is not a fringe or purely experimental treatment. It sits at the developing edge of a broader approach to care — one that brings together medicine, psychology, context and the therapeutic relationship.
The question is not whether psychiatry or psychotherapy has the better answer. It is how medical and psychological expertise can be brought together around the needs of one person.
OUR POSITION
The Emerge Clinic operates as a specialist KAP provider — not as a psychiatric service, and not as a ketamine infusion clinic. That distinction is deliberate and clinically important.
We provide psychotherapy and programme coordination. Medical assessment, prescribing, and administration are provided under the oversight of Dr Adam Devany, our Medical Lead and Prescriber. This separation reflects the genuine distinction between psychotherapeutic and medical expertise, and ensures that both components of a KAP programme are delivered by the right people, within their own professional domains and regulatory frameworks.
We work alongside psychiatric services rather than instead of them. Where a patient has an existing psychiatric team, we communicate with them. Where we identify a presentation that requires psychiatric input before proceeding, we say so clearly — and we help them think about what next step would actually serve them.
Our aim is to provide clear, rigorous and balanced care, so that people can make informed decisions based on understanding rather than marketing.