Pharmacotherapy and Ketamine Assisted Psychotherapy for Treatment-Resistant Depression: A Patient With Lifelong Self-Doubt and Self-Criticism (Yeung, et al, 2023)
Ketamine, an NMDA receptor antagonist, is not considered a classic psychedelic. Yet, it has similar dissociative effects that have been observed to bring relief from negativity, increase openness, promote communication, provide access to difficult materials with less fear, offer relief from obsessive and depressive concerns, and integrate a sense of newness and healing.19 These properties make ketamine an excellent candidate for PAP, and, currently, ketamine is the only legal psychedelic medicine available to mental health providers for the treatment of TRD. Ketamine assisted psychotherapy (KAP) has been used for patients suffering from a variety of disorders, including MDD, PTSD, bipolar I and II disorder, obsessive-compulsive disorder (OCD), and substance use. While the literature on KAP is small, it shows promise as a novel intervention to be explored further in many treatment-resistant clinical conditions.23 Similar to PAP, KAP clinicians meet with patients for 1–3 preparatory sessions to educate them about potential effects of ketamine, inform them about what happens during medication sessions and how best to engage in treatment, and guide them to select the psychological issues they want to focus on during medication treatment. In the first session, ketamine is usually given at a low sublingual dose to gauge the patient’s response, such as emotional changes, access to memories, or gaining new insights. In subsequent ketamine sessions, the doses will be titrated to optimize the patient’s therapeutic outcomes, which are frequently related to the levels of consciousness change. The therapists will then meet with the patient for “integration” sessions to process their experience in the ketamine sessions, as well as generate meanings and insights to be integrated into their cognitive framework.
Ketamine as Psychoplastogen
Ketamine’s Role in Spirituality: How One Synthetic Drug Catalyzes a Natural Experience (Woods, 2020)
This article highlights the potential spiritual effects of a popular anesthetic, ketamine, and how these spiritual effects can be used to help promote the reconciliation of spiritual and physical health. Ketamine, like the prominent psychedelic, psilocybin, has reportedly caused feelings of spiritual revelation and “out of body experiences” that many physicians may not feel qualified to discuss with their patients. This reluctance to address ketamine-induced spiritual experiences may affect the health outcomes of the patient. The primary goal of this project is to bring academic validity to considerations of the spiritual health of patients. This paper (1) investigates the extent that ketamine-induced, non-ordinary experiences can help bring awareness to the compatibility of spiritual and physical health and (2) compares the mechanisms of ketamine and psilocybin, as well as their value to the medical community due to the spiritual experiences that they catalyze. Thus, this research seeks to demonstrate that understanding the spiritual value of ketamine may encourage better communication between the physician and patient and promote more holistic healthcare approaches.
Ketamine-Assisted Psychotherapy Provides Lasting and Effective Results in the Treatment of Depression, Anxiety, PTSD at 3 and 6 Months: Large Retrospective Effectiveness Study (Yermus, 2024)
KAP produced sustained reductions in anxiety, depression, and PTSD, with symptom improvement lasting well beyond the duration of dosing and integration sessions. These effects extended to as much as 5 months after the last KAP session. However, the high rates of attrition may limit validity of the results. Given the growing mental health care crises and the need for effective therapies and models of care, especially for intractable psychiatric mood-related disorders, these data support the use of KAP as a viable alternative. Further prospective clinical research should be undertaken to provide evidence on the safety and effectiveness of ketamine within a psychotherapeutic context.
Psychedelic assisted therapy for major depressive disorder: Recent work and clinical directions (McCartney, 2022)
This review has examined the psychedelic treatment of MDD from a multifactorial perspective. A comparison of recent clinical trials shows that the psychological component of psychedelic treatment is vital for sustaining antidepressant outcomes. This aligns with the emerging biological understanding of these substances, specifically, their capacity to induce a period of neural plasticity that enhances the opportunity for emotional, cognitive, and behavioural repatterning. Given the bias towards a medical treatment model caused by the socio-political history of psychedelics, as well as flat out ignorance of their longstanding medicinal uses in cultures across the world, future research would benefit from more deliberately considering the importance of combined psychological and psychedelic therapy. Arguably, as these substances become increasingly legalised in a medical context, and thereby accessible to the public, psychedelic therapy will become less stigmatised. Until then, acknowledgment in clinical research and by practitioners of the dual importance of biological and psychological factors, could help to present a united front that actively works to align public perception of psychedelic treatment with its true therapeutic potential.
Ketamina no parenteral para la depresión: una discusión práctica sobre el potencial de adicción y recomendaciones para una prescripción juiciosa (Swainson, et al, 2022)
La ketamina sublingual es más biodisponible (30%) que la ketamina oral (20%). Un estudio reciente describió la seguridad y eficacia de la ketamina intravenosa a dosis de 0,5 mg/kg y 1,0 mg/kg y ningún beneficio para dosis más bajas. Esto se traduce en 1,5 o 3,0 mg/kg si se administra por vía sublingual, y 2,5 o 5,0 mg/kg si se administra por vía oral. Con esto en mente, solo 24,5 de los 7 estudios retrospectivos de la revisión sistemática incluyeron pacientes con ketamina en dosis adecuadas. Todos los demás estaban por debajo de las dosis equivalentes esperadas de SL y orales. Dos estudios prospectivos también administraron una dosis insuficiente de ketamina a dosis de 25 mg dos veces al día o 0,5 mg/kg al día, y un estudio prospectivo utilizó una dosis diaria total potencialmente adecuada de 50 mg tres veces al día, pero las dosis divididas pueden haber contribuido a una respuesta de ketamina reducida o más lenta.
Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression (Parikh, et al, 2024)
Resultados clínicos del tratamiento con ketamina intravenosa para la depresión en el sistema de salud VA (Pfeiffer, et al, 2024)
Intravenous (IV) ketamine is effective for reducing symptoms of major depressive disorder in short-term clinical trials; this study characterized clinical outcomes of repeated infusions in routine clinical practice and the frequency and number of infusions used to sustain symptom improvement. Methods: Records of IV ketamine infusions for depression and associated Patient Health Questionnaire-9 (PHQ-9) scores were identified from Veterans Health Administration (VA) electronic medical records for patients treated in Fiscal Year 2020 and up to 12 months following the date of their first infusion. Results: Sample patients (n = 215) had a mean baseline PHQ-9 score of 18.6 and a mean of 2.1 antidepressant medication trials in the past year and 6.1 antidepressant trials in the 20 years prior to their first ketamine infusion. Frequency of infusions decreased from every 5 days to every 3–4 weeks over the first 5 months of infusions, with a mean of 18 total infusions over 12 months. After 6 weeks of treatment, 26% had a 50% improvement in PHQ-9 score (response) and 15% had PHQ-9 score ≤ 5 (remission). These improvements were similar at 12 and 26 weeks. No demographic characteristics or comorbid diagnoses were associated with 6-week PHQ-9 scores. Conclusions: While only a minority of patients treated with IV ketamine for depression experienced response or remission, symptom improvements achieved within the first 6 weeks were sustained over at least 6 months with decreasing infusion frequency. Further study is needed to determine optimal infusion frequency and potential for adverse effects with repeated ketamine infusions for depression. J Clin Psychiatry 2024;85(1):23m14984 Author affiliations are listed at the end of this article.