Food fell out of the refrigerator. For most people, this is mildly annoying. For Dr. David Feifel's patient, it used to be catastrophic.

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This man's depression showed up as irritability. Any small frustration triggered yelling, profanity, hours of dysregulation. Then during TMS treatment, the refrigerator spilled. He picked up the food, put it back, moved on.

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His wife stood there in shock. She'd been bracing for the explosion that never came.

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That's impulse control returning. That's the prefrontal cortex doing its job again. That's just one of the things TMS does. But it's only half the story.

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On a recent discussion hosted by the Psychedelic Medicine Association (PMA), Will Sauvé, MD, Osmind's Chief Medical Officer, and David Feifel, MD, founder of Kadima Neuropsychiatry Institute, explore how combining two breakthrough treatments—ketamine and TMS—can provide what neither offers alone: immediate relief plus lasting resilience.

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Here's what you'll learn:

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• How ketamine and TMS work through different mechanisms (psychological flexibility vs. executive function)
• Which patients benefit most from combination therapy (acute crisis, trauma-based depression, partial responders)
• The optimal sequencing strategy based on clinical urgency and insurance coverage
• Why patients attribute different benefits to each treatment
• Insurance coverage realities and the Spravato access equation
• Clinical decision frameworks for real-world implementation

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Should I Combine Ketamine and TMS for Treatment-Resistant Depression?

Combining ketamine and TMS for treatment-resistant depression is clinically appropriate when patients need both rapid symptom relief (ketamine's strength) and sustained improvement (TMS's strength). Ketamine provides relief within hours to days but requires maintenance, while TMS takes 3-6 weeks to show results but produces longer-lasting effects. This combination works best for acute crisis patients, trauma-based depression, and those with partial response to either modality alone.

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How do ketamine and TMS work differently for depression?

Ketamine provides rapid relief by creating psychological flexibility—patients can access and process emotions that were previously blocked. TMS works more gradually by stimulating the dorsolateral prefrontal cortex, strengthening executive function, impulse control, and mood regulation through repeated daily sessions over 3-6 weeks.

Dr. Will Sauvé calls it "cookies and milk"—(when indicated), they're just better together.

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What ketamine does: Opening the window

Dr. Feifel describes a patient who'd tried everything—multiple medications, therapy programs. Nothing worked. Then during one ketamine treatment, he felt pleasure for the first time in decades. His response: "Oh my God, for the first time I know why people would go out to dinner."

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He'd spent his entire adult life wondering why people bothered with restaurants or movies. The effort seemed pointless. There was no reward on the other side. Even if that relief doesn't last permanently, he now knows his brain has that capacity. The switch exists. It worked once. That knowledge alone can be transformative.

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What TMS does: Building the infrastructure

TMS is like physical therapy for your brain. An electromagnetic field stimulates specific brain regions—usually the left dorsolateral prefrontal cortex for depression. No surgery, no pain, just a tapping sensation on the scalp.

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This region controls executive function, mood regulation, and impulse control. Patients don't report sudden mood changes day to day. But then something happens that would have derailed them for hours, and they just handle it.

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Back to that refrigerator moment: That's neural circuitry rewiring. It took three to six weeks of daily sessions to build, but once it's there, it sticks around. One patient told Dr. Sauvé: "All the TMS in the world isn't gonna make your boss less of a jerk. But now I have the guts to tell people how it's gonna be."
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Ketamine vs Spravato vs TMS: Timeline and Mechanism

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Which patients benefit most from combining ketamine and TMS?

Combination therapy is most beneficial for: (1) patients in acute crisis with chronic depression who need immediate stabilization while building long-term resilience, (2) trauma-based depression where ketamine provides psychological flexibility for processing while TMS strengthens executive capacity, and (3) treatment-resistant patients with partial response to either modality alone.

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Treatment-resistant depression doesn't equal severe depression. Failing two SSRIs doesn't make you twice as sick as someone who responds to the first medication. Someone can be treatment-resistant with manageable symptoms. Someone else can be severely depressed on their first episode.

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The distinction matters because it changes which interventions you deploy and when.

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Acute crisis + chronic depression

"Severe inpatient depression is a psychiatric emergency," Dr. Sauvé says. "That's a brain that's inflamed, swimming in cortisol, dying in front of you." You can't wait 3-6 weeks for TMS to work when someone's in danger. Start ketamine immediately for crisis stabilization while TMS builds long-term resilience in parallel.

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Trauma-based depression

TMS won't make you forgive your ex or reprocess childhood abuse. It's not going to resolve the content of trauma. But it will strengthen your capacity to implement the insights you gain. Ketamine can shift your relationship to traumatic experiences from "this controls my life" to "this happened to me." It creates the psychological flexibility to actually process difficult material.

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Combined, ketamine provides the window for processing while TMS builds the executive infrastructure to translate insights into sustained behavioral change.

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Treatment-resistant depression without acute severity

Someone failed four SSRIs but isn't in crisis. Start with TMS as the foundational treatment. Save ketamine for if/when you need faster intervention or if TMS produces partial but incomplete response. This sequencing maximizes insurance coverage (TMS is covered, ketamine often isn't) while building durable improvement first.

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What's the optimal sequence for combining these treatments?

For acute cases: start ketamine immediately for crisis stabilization, then initiate TMS within 1-2 weeks while continuing ketamine maintenance. For non-acute treatment-resistant depression: start with TMS as the foundational treatment, adding ketamine if partial response or if faster relief becomes necessary during the treatment course.

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The sequencing depends on four clinical factors:

1. What does this patient need right now? (Speed vs. durability)
2. What will they need in three months? (Crisis management vs. long-term stability)
3. What's the primary pathology? (Trauma processing vs. executive dysfunction)
4. What can they access? (Insurance coverage vs. out-of-pocket capacity)

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Not everyone needs both. But when both fit the clinical picture, combination therapy offers what neither provides alone: immediate support while building lasting infrastructure.

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Do you offer ketamine, Spravato, and/or TMS at your practice or want to? Learn how Osmind proactively relieves administrative burden and helps your practice grow.
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Are ketamine and TMS covered by insurance?

TMS is covered by most commercial insurance plans, Medicare, and Medicaid—typically requiring documentation of two failed antidepressant trials.

IV/IM ketamine is generally not covered and remains out-of-pocket ($400-800 per session). Esketamine (Spravato) is FDA-approved and insurance-covered, making it more accessible for combination therapy.
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The coverage disparity creates a predictable problem: patients delay ketamine treatments longer than optimal because of cost. They stretch time between sessions, compromising benefit to manage budget.

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Spravato changed this dynamic. Dr. Feifel calls it "the tortoise to ketamine's hare"—it works more slowly and less dramatically in his experience. But because patients can afford consistent visits every 2-3 weeks for months, they show gradual baseline lifting that sometimes surpasses sporadic ketamine.

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"It's never just about the drug," Dr. Feifel says. "It's about the context of the drug." Consistency often matters more than peak intensity. Access determines outcomes as much as mechanism.

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Does rapid improvement from ketamine carry psychological risks?

Rapid improvement from ketamine does not appear to carry significant psychological risks in clinical practice. Some patients experience disorientation when symptoms improve quickly—they may interpret a single bad day as treatment failure rather than normal mood variation.

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Dr. Feifel sees the theoretical concern but hasn't watched it materialize in his practice.

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Someone depressed for 20 years doesn't immediately understand that feeling down on Tuesday doesn't predict Wednesday. That reprogramming takes time. It's not a complication of the treatment—it's part of the recovery process.

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But rapid improvement offers something invaluable: proof the brain can still feel good. Many patients have wondered if they permanently lost that capacity. One ketamine session that produces even temporary relief shows them the switch still exists.

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That knowledge changes everything, even if the effect fades. It reframes the goal from "learn to live with this" to "figure out how to access that state consistently."

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What do patients report when doing both treatments?

Patients consistently attribute different benefits to each treatment: TMS improves executive function and impulse control ("I didn't explode at my boss"), while ketamine restores hedonic capacity and emotional access ("I understand why people enjoy concerts now"). This suggests genuine complementarity rather than redundant mechanisms.

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After TMS: "I would've exploded at my boss. Instead, I just walked away and handled it later."

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After ketamine: "I understand why people enjoy concerts now. The experience was actually pleasurable."

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These represent different dimensions of recovery—executive control versus emotional access, cognitive resilience versus hedonic capacity. Both matter for functional recovery, but they're not the same thing. "We need treatments that do different things," Dr. Feifel says. "We don't want 20 things that are essentially the same with different brand names."

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Frequently Asked Questions about combining ketamine and TMS

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Can a patient do ketamine and TMS on the same day?

Yes, there are no known contraindications to receiving both treatments on the same day. Many clinics schedule them separately (e.g., TMS in morning, ketamine in afternoon) to allow monitoring between sessions and avoid patient fatigue.

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How long should a patient continue each treatment when combining them?

TMS typically involves 30-36 sessions over 6-9 weeks for initial treatment. Ketamine maintenance varies by patient but often ranges from weekly to monthly sessions. Your psychiatrist will adjust frequency based on sustained response.

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Will insurance cover both treatments simultaneously?

Insurance typically covers TMS for treatment-resistant depression (after two failed antidepressant trials). IV/IM ketamine remains mostly out-of-pocket at $300-800 per session, though esketamine (Spravato) is FDA-approved and covered by many plans.

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Which treatment should I start first?

For acute crisis: start ketamine immediately for rapid stabilization, then add TMS within 1-2 weeks. For chronic treatment-resistant depression without acute severity: start TMS as the foundation, adding ketamine if needed.

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Are there patients who shouldn't combine these treatments?

Both treatments have excellent safety profiles with few contraindications. TMS is contraindicated for patients with metallic implants in the head/neck. Ketamine requires careful monitoring for patients with uncontrolled hypertension or history of psychosis.

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How do I track which treatment is helping?

Use measurement-based care with validated assessment tools (PHQ-9, MADRS, GAD-7) administered before each session. Osmind automates this tracking with built-in assessments, automated scoring, and progress visualization that shows symptom changes over time.

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The Clinical Decision

Back to that refrigerator story. The man’s wife was shocked because her husband had changed. Not temporarily. Not performatively. Actually changed.

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That's what we're after: functional recovery that sticks. Ketamine opens the door. TMS builds the foundation. Together, they offer immediate support while constructing lasting infrastructure.

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As Dr. Feifel puts it: "We need treatments that do different things. We don't want 20 things that are essentially the same with different brand names."

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Depression is complex. Treatment should match that complexity.

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Thank you for reading. Please note that this article does not constitute medical, legal or financial advice or services. Our aim is to entertain and inform our readers. We recommend that you consult with a qualified healthcare provider prior to making any medical decisions or changing any medications or dosages. The opinions expressed in this podcast are solely those of the speakers and do not necessarily reflect the views or endorsement of their affiliated organizations.