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 and let it rest there as an agent that can provide rapid relief of depressive symptoms and suicidal ideation. This is essentially the somewhat static box that Spravado, the branded form of Ketamine, is locked into. Pharma 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 occur in the face of 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 drug to enhance and broaden its therapeutic effect. Pharma guidelines restrict the maker of the branded product from even mentioning these dimensions of use because of a lack of research with the branded product. This is a shame because the large community of therapists in mental health don't have access to information the pharmacologists are aware of. On the other hand, there is plenty of exciting research to talk about. A therapist's participation is crucial to enhance the effectiveness and breadth of potential of this Ketamine.

I attended the large psychedelic sciences conference in Denver in July and had the opportunity of hearing 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 in Krystal's talk is that one of the biological effects of Ketamine is to open up the possibility of activated memories during a treatment session being reconsolidated in a tamed manner providing therapeutic relief of PTSD symptoms, particularly hyper arousal. 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 benefit from these traditional psychological interventions, however, have been disappointing. In distinction to the above, Krystal has elucidated the biological underpinnings of a direct action of Ketamine on activated memories.

The researchers have been able to identify specific proteins and nerve terminal changes during and proximate to a Ketamine session that offers 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 where 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 the patient because of the changes in time and place from the actual event. The soldier can be invited to think of 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 s/he has in comparison to the vulnerability the was the 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 have the therapists have the opportunity to take advantage of the possibility of memories being therapeutically reconsolidated.

In our practice we are following up on 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 founded on generic Ketamine. We are on the threshold of an era in which Ketamine and related drugs are likely to provide enormous benefit to patients by exploiting their psychological potential. This benefit will likely be most enhanced via an integration of biological and psychotherapeutic approaches. It's time for therapists and psychiatrist to deepen their embrace in treating patients.

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