Combining ketamine with deep TMS: a new frontier in the treatment of depression

While combinations of therapies have long been part of my clinical practice, the specific modalities and medications used are still evolving. As research and innovation develop, so do the possible combinations. Recently, two approaches have attracted considerable attention for their potential to combine treatment of major depressive disorder (depression) and treatment-resistant depression (TRD): ketamine (including the FDA-approved intranasal form, esketamine/Spravato) and the FDA-approved deep transcranial magnetic stimulation (dTMS). Emerging evidence suggests that combining these interventions may improve treatment effectiveness and provide options for patients who have not responded to traditional treatments. To understand the promise of this approach, it is important to explore the mechanisms of each treatment, potential synergistic effects, limitations, and broader implications for mental health care.

How Ketamine and Deep TMS Work Together

Unlike commonly used oral antidepressants (often called selective serotonin reuptake inhibitors, or SSRIs), ketamine works through a different mechanism. It targets the glutamate pathway in the brain, which rapidly changes the balance of our brains. This unique approach can relieve symptoms of depression within hours, rather than the weeks typically required with traditional medications. Ketamine's rapid activation makes it particularly valuable for emergencies such as suicidal thoughts. However, its effects are often short-lived and require repeated treatments. This is where dTMS can have a synergistic effect.

Deep TMS is a non-invasive therapy that uses magnetic pulses to stimulate brain circuits involved in emotion regulation. Its benefits may take longer to show but can be longer-lasting, with some patients achieving complete remissions that can last from months to years. Together, these treatments offer complementary advantages: ketamine provides rapid symptom relief, while dTMS provides lasting improvements over time.

While the combination of these two treatments remains an area of ​​active research, growing evidence continues to push the field forward. Some key patterns are emerging that excite me as a physician who sees patients who want their suffering to end sooner rather than later!

Why traditional antidepressants are not enough

Despite advances in understanding and diagnosis, depression remains one of the most common mental illnesses in the United States. While there are a variety of reasons, the United States appears to be fighting an uphill battle against this disease, from provider shortages to a lack of access. One major reason is that many patients simply aren't receiving the right treatments. Thirty percent of people with depression suffer from TRD, which often indicates that medication alone isn't solving the problem or isn't enough.

If these needs are not met, the consequences go far beyond personal suffering. Depression has a significant impact on society, resulting in reduced productivity, increased healthcare costs, and a significant economic burden. Researchers estimate that 12 billion workdays and nearly $1 trillion are lost each year due to depression and anxiety alone.

As the global prevalence of depression continues to rise, increasing by 60% in the past decade, we can no longer wait or rely on solutions that we know are not enough.

Why don’t patients receive personalized mental health care?

I'm going to be blunt: lack of the best care is the single most important factor in patient suffering. Despite growing awareness of TRD and substantial clinical evidence supporting the use of therapies such as dTMS to treat TRD, insurance coverage remains inconsistent.

Many payers require a “fail-first” approach, meaning patients are forced to try and fail multiple standard antidepressants before more advanced treatments can be approved. Most worryingly, many patients with TRD are at increased risk for suicidal ideation and cannot afford multiple rounds of treatment.

Delays in accessing potentially life-saving care not only worsen patient outcomes but also place significant financial and emotional stress on those already struggling with severe depression. This also adds to the broader economic burden mentioned earlier.

The same challenges apply to ketamine treatment. While ketamine has been shown to have rapid antidepressant effects, coverage remains a barrier in many cases. While some policies allow the use of ketamine or dTMS alone, most do not cover combinations, which in many cases is a treatment option patients may need. We often refer patients to hospitals that do not offer either treatment. This is the worst of all possible worlds.

The next frontier of mental health

The combination of ketamine therapy and dTMS represents a possible future of neuromodulation, with innovative treatments that could improve quality of life and reduce costs. Clinical research is increasingly focusing less on whether depression can be treated and more on how care can be delivered more effectively than the current standard.

However, what is progress without a fair chance? That was a hollow victory. Payment models and healthcare infrastructure have failed to keep pace with scientific breakthroughs. This results in too many patients being left behind. Our challenge now is to align science, policy, and clinical practice so that innovative treatments like ketamine and dTMS are available to the patients who need them most, when they need them.

Photo: wildpixel, Getty Images

This article appeared in Medical City Influencers program. Anyone can share their thoughts on healthcare business and innovation on MedCity News through MedCity Influencers. Click here to learn how.