- M.E.G. Kongress 2025, Vortrag „Ketamin-augmentierte Psychotherapie (KAP)“ von Prof. Dirk Revenstorf, 30.03.2025
Ketamine, originally developed as an anesthetic, has gained increasing attention in recent years as a promising treatment for treatment-resistant depression (TRD) and other psychiatric disorders. Currently, ketamine is the only psychedelic drug that can be used legally.1
While ketamine alone can provide rapid symptom relief, evidence suggests that combining it with psychotherapy, known as ketamine-augmented psychotherapy (KAP), can lead to more sustainable and comprehensive treatment outcomes.1
The number of publications on the use of ketamine in a therapeutic context has also been growing in recent years.2 Is this just a new hype from the past, or is there something to the new trend in drug therapy? Prof. Dirk Revenstorf presented current data and analyses in his lecture at the M.E.G. Annual Congress.
In general, psychedelics such as psilocybin, mescaline, LSD, MDMA, or ketamine affect the brain by altering serotonin and dopamine release and thus the level of arousal in the brain.
Ketamine acts primarily as an NMDA receptor antagonist, leading to increased glutamate release and subsequent AMPA receptor activation. NMDA receptor blockade also affects pain transmission. Furthermore, these mechanisms can promote synaptic plasticity and increase neuronal connectivity, possibly explaining its antidepressant effects.3 Furthermore, ketamine increases levels of brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of neurons.
One study showed that ketamine (and other psychedelic substances) causes increased activity in certain brain regions, particularly the occipital-parietal area.4
These neurophysiological processes induce dissociative effects and influence the filtering of external stimuli as well as the integration of sensory input. Furthermore, there is an increase in the production of internal stimuli, so that expanded physical experiences can usually be had and an increased number of internal images arise. Overall, the experience and processing of mental processes are more imaginative and associative. During the session, patients can experience a "time-out" from everyday thinking, a break from negativity, and access to an expanded understanding of themselves and their relationship to the world.1 This can open up space for new evaluations.
Cahart-Harris et al. (2014) state that the brain normally creates "models" of the environment in order to predict actions and reactions of the environment. Psychoactive substances could intervene at this point and increase entropy in the brain, thus explaining the described disintegration of the structure and boundaries of the ego.5
Traditional selective serotonin reuptake inhibitors (SSRIs) block the reuptake of serotonin or dopamine. These medications generally tend to dampen patients' emotions. In contrast, psychedelics like ketamine enhance synaptic signaling and boost BDNF levels, thus acting more as emotion enhancers.
Some meta-analyses also show that traditional antidepressants are barely more effective than placebo.6,7,8 This topic remains controversial in the scientific community. What is certain is that the effectiveness of SSRIs may depend heavily on the severity of depression, that the placebo effect can play a major role in the treatment of depression, and that the effectiveness of SSRIs is likely to vary greatly from person to person.
SSRIs therefore have limited efficacy. Increasing numbers of patients in need of therapy and long waiting times for therapy places make it understandable why new-old hopefuls such as psychedelics are being (re)investigated.
Ketamine therapy is currently legalized off-label in Germany for TRD, post-traumatic stress disorder (PTSD), substance use disorders, anxiety disorders, and obsessive-compulsive disorders.
Contraindications for the use of ketamine include psychotic illnesses, severe cardiovascular disease, substance dependence, and pregnancy. It should also be noted that there are so-called non-responders who cannot benefit from ketamine therapy at all.
Ketamine can be administered intravenously, intramuscularly, sublingually, or intranasally. Intravenous administration is considered standard.9 Therapeutic support before and after the session is important for sustained integration of the experience and promoting acceptance of the results.
Psychotherapeutic support for KAP usually involves CBT, sometimes also mindfulness-based behavioral therapy or depth psychology. Therapy sessions can be preparatory, subsequent to, and/or during, the ketamine session.10
Studies show a significant decrease in depression and anxiety parameters after KAP compared to before therapy.11 Severely depressed patients also showed significant improvements in symptoms after KAP compared to treatment as usual (TAU).9
Patients report major changes in their lives after ketamine-augmented psychotherapy, a changed perspective, and the transformation of internal conflicts that have sometimes persisted for years.
Ketamine-augmented hypnotherapy can also be an approach. The hypnotic trance is similar in some aspects to dreams and psychedelic experiences and can be used therapeutically in a targeted and supportive way to work regressively or biographically and to activate resources.
The antidepressant effect of ketamine lasts for a few days to weeks. Similar data, but from fewer studies, have also been found for anxiety disorders, obsessive-compulsive disorder, and bipolar depression.
Therapeutic support can prolong the effects, but relapses are common.9
Ketamine can cause a number of side effects, including dissociation, increased blood pressure and heart rate, nausea and vomiting, insomnia, sleep disturbances, and anxiety and panic. In rare cases, psychotic symptoms may also occur.
Long-term use may cause bladder problems due to ketamine's toxicity to bladder cells.12
KAT represents a promising approach for the treatment of TRD and other psychiatric disorders. While the body of evidence continues to grow, available data suggest that combining ketamine with psychotherapy can lead to more sustainable and comprehensive treatment outcomes. Careful patient selection, education, monitoring, and psychotherapeutic support are crucial for the safe and effective use of KAT in clinical practice.
Further studies are needed to investigate the long-term added value of KAT. While the existing data suggest a certain therapeutic potential, the extent to which ketamine use produces long-term effects and the associated safety profile require further investigation. However, the results to date warrant further research, particularly in treatment-resistant cases.