In psychiatry, ketamine is considered a substance with a rapid onset of antidepressant action, with administration potentially leading to clinical improvement within hours to days. In addition to its pharmacological use, ketamine-assisted psychotherapy (KAP) has developed in recent years. This approach combines the biological effects of the substance with targeted psychotherapeutic work and aims to prolong and deepen the antidepressant response.
At subanesthetic doses, ketamine is used for its rapid antidepressant and anti-suicidal effects. Unlike conventional antidepressants, symptom relief often occurs within a few hours after administration. However, this effect is time-limited; in most patients it persists for days to weeks. Without a follow-up strategy, symptoms typically gradually return, necessitating repeated intervention.
The mechanism of action of ketamine includes NMDA receptor antagonism, modulation of glutamatergic neurotransmission, and subsequent activation of pathways associated with synaptic plasticity and the weakening of rigid cognitive and emotional patterns. After the acute effects subside, a period of increased neuroplasticity lasting 1–2 weeks follows, referred to as the afterglow, characterized by improved mood, greater optimism, increased energy, and openness.
KAP utilizes the pharmacological effects of ketamine as a means of facilitating the psychotherapeutic process. The altered state of consciousness induced by ketamine is viewed in this context as a potential facilitator of introspection, emotional processing, and work with maladaptive patterns of experience and behavior. KAP thus differs from purely biological ketamine administration, where the altered state of consciousness is regarded primarily as an undesirable side effect.
KAP is structured into three phases. The preparatory phase serves to define therapeutic intentions, educate the patient, and establish a safe therapeutic environment. This is followed by the ketamine session itself, during which significant emphasis is placed on appropriate environmental settings and patient support throughout the substance’s effects (set and setting).
For example, music may be used during the session to support introspective experiences, guide attention, and deepen the therapeutic process. In some cases, patients are given the same playlist to listen to at home to support subsequent therapeutic work. The third phase, integration, focuses on processing the experience and incorporating it into longer-term therapeutic goals.
In the Czech Republic, psychedelic-assisted therapy includes not only ketamine—registered as a medicinal product and used off-label in psychiatry—but also psilocybin, which is a controlled substance with strictly defined indications. Unlike dissociative ketamine, the antidepressant effects of serotonergic psilocybin persist significantly longer, lasting weeks to months. These effects and their duration in treatment-resistant depression are being compared in an ongoing study at the National Institute of Mental Health (NIMH-CZ).
Ketamine is most commonly considered for patients with treatment-resistant depression. Current scientific evidence further suggests its efficacy across a broader spectrum of mental disorders, including anxiety disorders, post-traumatic stress disorder, obsessive-compulsive disorder, and eating disorders. This is where KAP may have a clinical role.
However, relatively few scientific studies have examined ketamine in the context of psychotherapy, likely due to high financial demands and the difficulty of standardizing methodologies for such evaluations.
In clinical practice, ketamine—and especially its psychotherapeutically assisted use—is generally indicated only after standard treatment approaches have failed. KAP should be conducted at specialized centers with appropriate professional expertise and clearly defined indication and safety criteria.
Available data provide a sufficient basis for the off-label use of ketamine in affective and anxiety disorders and indicate promising potential for its psychotherapeutically assisted application.
Further development of KAP will depend on systematic clinical research, methodological standardization, the development of specialized teams, and the establishment of a clear organizational and economic framework that would enable its full integration into clinical practice.
Editorial Team, Medscope.pro
Sources:
1. Tylš F. Ketamine-assisted psychotherapy in clinical practice. Psychiatrie 2025;29(1):15–22. 2. Psilocybin versus ketamine: strategies for rapid antidepressant response in treatment-resistant depression (PSIKET_001CZ). NIMH-CZ. Available at: www.nudz.cz/vyzkum/centrum-vyzkumu-psychedelik/granty-a-projekty/psilocybin-versus-ketamin-strategie-rychle-antidepresivni-odpovedi-u-deprese-rezistentni-k-lecbe 3. In detail about KAT treatment with psychologist and therapist Mgr. Vojtěch Viktorín. Psyon. Available at: www.psyon.cz/bst-podcast-podrobne-o-lecbe-kat-s-psychologem-a-terapeutem-mgr-vojtechem-viktorinem
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