Ketamine, a Drug Encouraging Psychiatrists and Therapists to Join Hands.

There are a number of perspectives on Ketamine as a therapeutic agent. One is to marvel at its biological activity, being an agent that can provide rapid relief of depressive symptoms and suicidal ideation. This is essentially the somewhat static box that Spravato, the branded form of Ketamine, is locked into. Pharmaceutical guidelines require its use under a so-called risk management system that restricts its use to just two indications: treatment-resistant depression and suicidality.

These restrictions exist despite decades of research on the generic drug, which shows it has significant potential in a number of conditions, particularly PTSD and addictions. There is a strong clinical movement to integrate the psychological potential of Ketamine to enhance and broaden its therapeutic effect. Pharmaceutical guidelines restrict the maker of the branded product from even mentioning these dimensions of use due to a lack of research with the branded product. This is unfortunate because the large community of therapists in mental health does not have access to information that pharmacologists are aware of. On the other hand, there is plenty of exciting research to discuss. A therapist's participation is crucial to enhancing the effectiveness and breadth of Ketamine's action.

I attended the large psychedelic sciences conference in Denver in July and had the opportunity to hear an update on Ketamine from John Krystal, the well-known basic science psychiatric researcher who has been working with Ketamine for over 20 years. His talk emphasized the importance of integrating the drug with counseling in the treatment of PTSD.

The idea presented by Krystal is that one of the biological effects of Ketamine is to allow the possibility of activated memories during a treatment session to be reconsolidated in a tamed manner, providing therapeutic relief of PTSD symptoms, particularly hyperarousal. Patients with PTSD tend to have an overactive hypothalamus. Krystal and allied researchers, using sophisticated imaging tools, have been able to identify circuits that can favorably modulate this hyperactivity. One set of connections in the brain comes from the frontal lobes. These circuits are likely engaged when a patient experiences traditional counseling interventions for trauma. The benefits of these traditional psychological interventions, however, have often been disappointing. In contrast, Krystal has elucidated the biological underpinnings and the probability that Ketamine has a direct action on activated memories.

The researchers have identified specific proteins and nerve terminal changes during and after a Ketamine session that offer the promise of allowing disturbing memories to be reframed in helpful therapeutic ways. There appears to be a time-dependent window during which this can occur. It is here that therapists can facilitate the process of these memories being therapeutically reconsolidated.

During his talk, Krystal advocated a kind of exposure technique in which the patient is invited to invoke a traumatic memory as Ketamine is being administered. Reframing is encouraged as the patient is invited to reconsider the trauma in terms of the perspective that is available to them due to the changes in time and place from the actual event. For example, a soldier can be invited to reflect on the relative safety of civil society away from the battlefield, or an adult suffering the effects of childhood trauma can be reminded of the maturation and skills they have developed compared to the vulnerability that was their reality when harm originally occurred.

In a published paper referenced below, Krystal points out that there is a limited time period lasting only a couple of days within which therapists have the opportunity to take advantage of the possibility of memories being therapeutically reconsolidated.

In our practice, we are following Krystal's lead by having patients return for a post-Ketamine interview within 48 hours of exposure to the drug. The idea is that creative and healing perspectives that patients arrive at under the influence of the drug can be validated and reinforced during the therapeutic window when the patient is fully sober.

There is a large and growing movement of Ketamine-assisted therapy, or KAP, most of which is based on generic Ketamine. We are on the threshold of an era in which Ketamine and related drugs are likely to provide enormous benefits to patients by exploiting their psychological potential. This benefit will likely be most enhanced through an integration of biological and psychotherapeutic approaches. It is time for therapists and psychiatrists to deepen their embrace of this approach in treating patients.

Those wanting to dig down deeper can reference one of Krystal's papers below

Ref: https://doi.org/10.1038/s41386-023-01606-3