Charting a remarkable path across the terrain of mental health, Dr. Toby Marton, M.D., PhD., has bridged the gap between neuroscientific research and clinical psychiatry. With his dual MD and Ph.D. from UC San Diego, a residency at UCSF, and subsequent research as an NIMH-funded fellow, Toby has not only expanded our understanding of mental health but also contributed immensely to its practical application.

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In this conversation with Dr. Tobias Marton, we delve into a range of topics at psychiatry's frontier:

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• His career path to become CMO of a major national mental healthcare company.

• Perspectives on the relative strengths and shortcomings of 3 major interventions for treatment-resistant depression (TRD) and PTSD.

• Age and Patient Responsiveness to ketamine: Gain insights into how patient age impacts the response to ketamine infusions.

• Tech Solutions in Mental Health Care: Discover the role technology can play in scaling the provision of psychedelic-assisted therapy.

• Toby’s vision of the future of psychiatry.

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Join us as we uncover Dr. Marton's unique vision for the future of psychiatry.

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Career: from clinician to scientist to CMO at Minful Health Solutions

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Inspired by shows like ER and his stint at a biotech firm, Toby's initial pull towards medicine was infused with a deep fascination for the human brain. This interest guided his journey through pre-med at UC Berkeley, leading him to specialize in neuroscience research and ultimately culminating in his choosing psychiatry as his path. The allure of psychiatry lay in its unique blend of narrative understanding of patients and grappling with the intricacies of human consciousness.

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After medical school and a PhD in neuroscience, Toby pursued his vision of becoming a research-based resident at UCSF, exploring the world of optogenetic investigations of neural circuitry. Despite his intention to remain in the lab, an elective in ECT during his residency shifted his perspective. The transformative potential of psychiatric interventions was laid bare as he witnessed severely depressed patients make remarkable recoveries. This powerful experience contrasted starkly with the despair he'd sensed within the field, rooted in the limited effectiveness of existing interventions.

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Following his residency, a postdoctoral role seemed a natural fit, continuing his lab work while also giving him space to explore patient care. His curiosity led him towards the emerging fields of TMS and ketamine therapies. Intrigued by these new, potentially revolutionary treatments, Toby began to envision himself as an 'interventional psychiatrist,' determined to pioneer these methods despite his unfamiliarity with them.

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A golden opportunity arose when a position opened at the VA. Toby leapt at the chance, demonstrating his unyielding determination to build a TMS and IV Ketamine clinic from the ground up. Despite initial setbacks, he tirelessly reached out to experts, attended numerous conferences, and found invaluable mentorship. His unwavering dedication bore fruit as the programs at the VA flourished.

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Toby's time at the VA wasn't just about implementation, though. His scientist's curiosity drove him to collect and analyze extensive patient outcome data, leading to a series of research publications. This real-world impact on patients rekindled the spark that had initially drawn him to psychiatry, offering a fresh perspective on a field that had previously seemed mired in despair.

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As the global pandemic unfurled, Toby saw it as an opportunity for change, a catalyst for a shift from academia to the private sector. The dire need for effective treatments was undeniable. This realization, coupled with his firsthand experience with the transformative impact of new interventions, made Toby understand that he could make a more immediate impact in the clinical field than in academia.

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With this in mind, he joined Mindful Health Solutions, formerly TMS Health Solutions, a clinic quickly establishing itself as one of the largest esketamine providers in the country. Toby and his team were quick to adapt to emerging treatments, incorporating s-ketamine rapidly after its FDA approval in 2018. Their goal was simple yet ambitious: to remain at the forefront of psychiatric treatments while working within the framework of insurance-covered interventions.

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Here, Toby found the perfect setting to marry his passion for innovative treatment with the desire for patient-centric care. The emphasis was not on being a one-size-fits-all clinic but on carefully evaluating each patient and determining the best course of treatment.

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But this personalized approach was not without its challenges. As the field expanded to include treatments like psychedelics, Toby and his team had to navigate the complexities of deciding treatment sequences and combinations in the absence of clear-cut clinical algorithms. Factors such as patient preference, physician preference, cost, and logistics all had to be considered. However, Toby saw these challenges as opportunities, paving the way for fascinating studies in effective treatment algorithms and predictive models.

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Misconceptions Around Ketamine as an Opioid

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According to Toby, the representation of ketamine as an opioid often arises from misunderstandings and mischaracterizations. "Ketamine does interact with the opioid system weakly, but it isn't an opioid," he clarified, expressing his concerns about the "hysterical direction" the media took from a single study that hasn't been widely replicated.

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Toby underlined the need for further investigation, especially considering that patients treated with ketamine, including those on methadone and other opioid blockers, showed no difference in outcomes compared to patients not on these drugs. In his view, while ketamine may have some degree of agonism with the opioid system, it's not a straight line to categorizing it as an opioid.

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Patient Responsiveness to Ketamine Infusions and the Impact of Age

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On the topic of patient responsiveness to ketamine infusions, Toby reflected on his experiences with different patient trajectories. He spoke about patients responding to infusions in various ways — some showing rapid responses after the first infusion, while others might not show any response until the fourth infusion. However, Toby mentioned that they all eventually reached the same endpoint, albeit via different routes.

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He also noted a correlation between a patient's age and the speed of their response to treatment, indicating that older patients tended to respond slower.

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"What we found was that essentially as a function of age, you responded slower... Everyone that responded, responded. It just was a matter of time," he said, sparking curiosity about what these differing journeys could imply about individual neurobiology and neuroplasticity.

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Comparative Effectiveness: Ketamine vs. TMS vs. ECT for PTSD

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Toby then turned his attention to the effectiveness of various treatments for PTSD, particularly in the veteran population. He acknowledged that both Transcranial Magnetic Stimulation (TMS) and Electroconvulsive Therapy (ECT) had their merits, but in his experience, these treatments often didn't effectively address PTSD symptoms. According to Toby, "one of the real powers of IV ketamine" is its potential to treat cohorts of patients with severe PTSD symptoms.

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He further explained that, based on his experience, patients undergoing ketamine treatment often required maintenance or relatively frequent re-treatment. Toby stressed the temporal dynamics of depression and PTSD scale dropping in parallel for patients undergoing ketamine treatment, which he observed to be a powerful intervention for those with trauma.

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Shifting Landscapes: Insurance Approval for TMS and Esketamine

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A significant factor in the provision of mental health treatments is navigating the intricacies of insurance coverage. In recent years, the approval process for treatments like esketamine and Transcranial Magnetic Stimulation (TMS) has witnessed dynamic shifts. Notably, initially, it was considerably easier to secure approval for esketamine than for TMS, despite TMS' high bar of requiring four antidepressant failures—a benchmark that is frankly not evidence-based.

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However, as the landscape continuously evolves, there is evidence of increasing alignment amongst major payers. This shift represents a positive development, moving us closer to a reality where the complexities of insurance approval are less of a hindrance to patient care.

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Are ketamine and esketamine destined for a chronic care model? The Operational Challenge of scaling Mental Health Interventions

Delivering effective mental health treatments on a large scale poses operational challenges, particularly for interventions that require ongoing or chronic care. The current esketamine care model is a notable example, with the maintenance or regular re-treatment often needed, particularly for patients with severe PTSD symptoms.

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The Search for a Balanced Approach

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Providing inclusive care to numerous patients demands strategic planning. There’s no logical tree-chart-like  method to determine the optimal order and mix of treatments given the variety of effective options available and patient diversity.

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A pragmatic approach might involve starting with a treatment like TMS that has a (relatively) clear beginning and end, before transitioning to ongoing treatments like esketamine.

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The rate of new patients coming in for treatment can quickly outpace the rate of those completing their treatment. Without a systematic approach to discharge or extend treatments, an operation could gradually become overwhelmed, limiting its ability to provide comprehensive care to all its patients.

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Can we Harness Tech Solutions to Scale Psychedelic-Assisted Therapy?

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Turning to tech solutions, Toby expressed optimism for their potential to scale psychedelic-assisted therapy. The utilization of technology holds great promise in broadening the reach of psychedelic-assisted therapy. 

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Recent studies, like the one conducted by Rebecca Price, have begun exploring the impact of computer-based interventions like implicit association tasks on patients. Imagine the potential of integrating this training post-ketamine infusions or during TMS sessions to boost treatment durability.

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While further research is needed to replicate these initial findings, the prospect is thrilling. Technological interventions could dramatically improve the scalability of treatments.

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Looking forward, advances in AI-based therapy and coaching tools could help solve for obstacles inherent to providing psychedelic-assisted therapy, which often requires a full day's engagement per patient.

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Osmind is already exploring these possibilities, utilizing their patient-facing app to digitally deliver specific psychological or psychotherapy interventions. Osmind also has a dedicated journaling section in the patient app—a simple, yet potent tool for enhancing the therapeutic process.

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The Practial Way Psychedelics Could Streamline Mental Healthcare

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Finally, Toby touched on the potential benefits of psychedelics, expressing the hope that they could lead to less intensive treatment cycles in the long run. The promise of psychedelics, he noted, is the prospect that "you do this eight hours, but then maybe you're done for three or four months," an intriguing idea that challenges current models of mental health care delivery.

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Dr. Gul Dolen’s research supports the idea that longer subjective experiences, while intensive, may lead to more enduring antidepressant effects.

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The demand for face-to-face psychotherapy, especially within the psychedelic realm, often feels like a constraint, especially with the pressing need for on-site therapists.

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Summary and Conclusion:

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Dr. Toby Marton's multifaceted journey spans from an initial pull towards medicine due to shows like ER, through academia and neuroscience, to a pivotal role as CMO at Mindful Health Solutions. Driven by groundbreaking experiences in treating depression and a deep curiosity, Toby's work highlights:

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1. Ketamine is not strictly an opioid, and age affects responsiveness to ketamine treatments.
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2. Ketamine has shown promising potential in treating PTSD, often more effectively than TMS or ECT.
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3. The complexities of insurance approvals and the challenges in operational scaling of mental health interventions remain.
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4. Technological solutions, including AI-based tools, impliciat association tasks, and platforms like Osmind, promise to scale psychedelic-assisted therapies and potentially enhance treatment durability.
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5. The transformative potential of psychedelics lies in their ability to offer less frequent yet more intensive treatment sessions, potentially revolutionizing mental health care models.
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Want to delve deeper? Listen to the full discussion here:
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Shownotes/Timestamps:

3:00: Toby’s inspiration for pursuing Psychiatry and his choice for an MD in Psychiatry and a PHD in Neuroscience over neurology. His interest in consciousness as a complex subject.

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6:45: Toby discusses the prevalence of learned helplessness and nihilism in Psychiatry.

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7:40: Insights Toby gathered about the brain from Electroconvulsive Therapy (ECT).

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9:00: The motivations behind Toby's shift from bench research to clinical work.

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12:30: Exploration of Toby’s research on rapid-acting antidepressants and testing new treatments at the VA.

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14:16: Delving into the misleading interpretations of a Naltrexin paper which suggested that ketamine's action was akin to that of an opioid. This conclusion was drawn from a single study with a small sample size.

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18:31: Characteristics of patients who didn’t respond as quickly to ketamine treatments for Depression


29:14: The payer/operational decisions on which treatment to try first between ketamine, TMS, and esketamine

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37:57: Cosmetic psychiatry and discussion on if the dissociative experience is paramount to the antidepressant effects of ketamine

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42:40: Preparing for MDMA-assisted therapy45:02: Challenges of scaling psychedelic-assisted therapies and how tech can help.