Combining Ketamine and Deep TMS: A New Frontier in Treating Depression

While a combination of therapies has long been part of my clinical practice, the specific modalities and medications used continue to evolve. As the research and innovation grow, so do the possible combinations. Recently, two approaches have drawn significant attention for their potential in treating major depressive disorder (depression) and treatment-resistant depression (TRD) when combined: ketamine (including its FDA-approved intranasal form, esketamine/Spravato) and FDA-cleared, Deep Transcranial Magnetic Stimulation (dTMS). Emerging evidence suggests that combining these interventions may enhance treatment outcomes and provide options for patients who have not responded to traditional therapies. To understand the promise of this approach, it is important to explore each treatment’s mechanism, potential synergistic effects, limitations, and broader impact on mental health care.

How ketamine and deep TMS work together

Unlike commonly used oral antidepressants (often known as selective serotonin reuptake inhibitors or SSRIs), ketamine works through a different mechanism. It targets glutamate pathways in the brain, which work rapidly to change the balance in our brain. This unique approach can relieve depressive symptoms within hours, rather than the weeks traditional medications often require. Ketamine’s quick activation makes it especially valuable for urgent situations such as suicidal thoughts. However, its effects are often short-lived, requiring repeated treatments. This is where dTMS can play a synergistic role. 

Deep TMS is a noninvasive therapy that uses magnetic pulses to stimulate brain circuits involved in mood regulation. Its benefits may take longer to appear but can be more sustained, with some patients achieving complete remission that is durable for months to years. Together, these treatments offer complementary advantages: ketamine delivers rapid relief, while dTMS supports lasting improvement over time.

While the combination of these two treatments remains an area of active investigation, mounting evidence continues to propel the field forward. Several key patterns have emerged that excited me, as a physician who sees patients who want their suffering to end sooner, not later! 

Why traditional antidepressants aren’t enough

Despite advances in awareness and diagnosis, depression remains one of the most common mental illnesses in the U.S. While there are several reasons, America seems to fight an uphill battle with this illness, from provider shortage to lack of access, a major reason is that many patients are simply not receiving the right treatment. 30% of depressed patients have TRD, often signalling that medication alone is either not the answer or not enough.

The consequences of leaving these needs unmet extend far beyond individual suffering. Depression significantly impacts society, contributing to lost productivity, higher healthcare costs, and a massive economic burden. Researchers estimate that 12 billion workdays are lost each year to depression and anxiety alone, at a cost of nearly $1 trillion.

With the global prevalence of depression continuing to rise, increasing 60% in the past decade, we can’t afford to wait, nor rely on the same solutions we know aren’t enough. 

Why aren’t patients receiving personalized mental health care? 

I’m going to be blunt: lack of access to the best care is the most important factor in why patients suffer. Despite the growing recognition of TRD and overwhelming clinical evidence supporting therapies like dTMS in treating it, insurance coverage remains inconsistent. 

Many payers require a “fail-first” approach, which means patients are forced to try and fail multiple standard antidepressants before approving coverage for more advanced treatments. What’s of most concern is that many patients with TRD are at higher risk for suicidal ideation and cannot afford to cycle through multiple rounds of treatment. 

Delays in access to potentially life-saving care not only worsen patient outcomes but also add significant financial and emotional strain to those already battling severe depression. This also further compounds the broader economic burden noted earlier. 

The same challenges apply to ketamine therapy. While ketamine has demonstrated rapid antidepressant effects, coverage is still a barrier in many cases. And while some policies allow ketamine or dTMS individually, most do not cover the combination, which in many cases is a treatment protocol the patient might need. We are often stuck referring patients to hospitals that offer neither treatment. This is the worst of all possible worlds.

The next frontier in mental health 

The integration of ketamine therapy and dTMS represents one possible neuro-modulated future, where innovative treatments can improve quality of life and reduce costs. Clinical research is increasingly focused not on whether depression can be treated, but on how to deliver care more effectively than the existing standard.

However, progress without equitable access? That is a hollow victory. Payment models and healthcare infrastructure have not kept pace with scientific breakthroughs. This is leaving too many patients behind. Our challenge, now, is to align science, policy, and clinical practice so that innovative therapies like ketamine and dTMS are available to the patients who need them most – when they need them.

Photo: wildpixel, Getty Images

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