TMS vs. Ketamine: Which Treatment Is Right for Your Depression?

By Kyle Roth, FNP-BC, APRN, MSN, MHA | Roth Family Medicine and Mental Health | Pocatello, Idaho

If you've been told you have treatment-resistant depression and you're exploring options beyond antidepressants, you've likely encountered two names repeatedly: TMS (transcranial magnetic stimulation) and ketamine therapy. Both are evidence-based, FDA-cleared or approved treatments with strong clinical track records. Both offer hope to patients for whom conventional antidepressants have failed.

But they are not interchangeable. They work through different mechanisms, suit different patient profiles, have different practical requirements, and carry different cost and insurance implications. Understanding the differences is essential to making an informed decision — and to having a productive conversation with your provider.

Transcranial magnetic stimulation delivers focused, repetitive magnetic pulses to specific regions of the brain — primarily the left dorsolateral prefrontal cortex (DLPFC), a region consistently underactive in depression. The pulses stimulate neural activity in this region, gradually normalizing the functional connectivity patterns that depression disrupts.

TMS is non-invasive, non-systemic, and non-pharmacological. There is no drug involved, no anesthesia, and no systemic side effects. The treatment works through neuroplasticity — the brain's ability to reorganize itself in response to repeated stimulation.

The mechanism is cumulative. TMS doesn't produce an acute effect after a single session; it builds over a course of treatment, typically 20–36 sessions delivered over 4–6 weeks.

Key Reference: O'Reardon JP, et al. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depressive disorder: a multisite randomized controlled trial. Biological Psychiatry, 62(11), 1208–1216.

Ketamine works through a fundamentally different mechanism — NMDA receptor antagonism in the glutamate system. By blocking NMDA receptors, ketamine triggers a cascade of downstream effects that rapidly restore synaptic connectivity and promote neuroplasticity, particularly in the prefrontal cortex and hippocampus.

The result is an antidepressant effect that can emerge within hours to days of the first infusion — dramatically faster than any other treatment in psychiatry. This rapid onset is ketamine's defining clinical advantage.

Ketamine also has a direct, rapid anti-suicidal effect that is distinct from its antidepressant properties — a clinically significant advantage for patients in acute crisis.

Key Reference: Berman RM, et al. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351–354.

TMS is often the preferred first-line advanced treatment when:

• Insurance coverage is a priority — TMS is covered by most major insurance plans after documented failure of 2+ antidepressants
• The patient prefers a non-drug approach — TMS involves no medication, no systemic effects, and no altered consciousness
• The patient cannot tolerate dissociative experiences — some patients find the ketamine experience anxiety-provoking
• The patient has a history of substance use disorder — ketamine has abuse potential; TMS has none
• The patient has uncontrolled hypertension or cardiovascular risk — TMS has no cardiovascular effects
• The patient is pregnant or breastfeeding — TMS is generally considered safer in this context
• The depression is moderate in severity without acute suicidality — TMS is highly effective for this profile

Ketamine is often preferred when:

• Speed of response is critical — acute suicidal ideation, severe functional impairment, or a patient who cannot wait 4–6 weeks for TMS to work
• The patient has failed TMS — ketamine works through a completely different mechanism and can succeed where TMS has not
• The patient has PTSD alongside depression — ketamine has emerging evidence for PTSD that TMS does not yet match
• The patient has severe, treatment-refractory depression — ketamine's response rates in the most severe TRD cases are strong
• The patient prefers fewer total sessions — 6 infusions vs. 20–36 TMS sessions
• Spravato (esketamine) is an option — FDA-approved for TRD and covered by many insurance plans when administered in a certified setting

Yes — and this is an area of active clinical interest. Some patients receive ketamine to achieve rapid initial stabilization, then transition to TMS for sustained maintenance. Others receive TMS as the primary treatment and use ketamine for breakthrough episodes.

The two treatments are not mutually exclusive and can be sequenced or combined based on individual patient needs.

TMS requires daily sessions (Monday–Friday) for 4–6 weeks. For patients in Pocatello and Southeast Idaho, this means 20–36 trips to the clinic. This is manageable for many patients but can be a barrier for those with demanding work schedules, caregiving responsibilities, or transportation challenges.

Ketamine requires 6 sessions over 2–3 weeks, with each session lasting approximately 2 hours including recovery. The total time commitment is significantly lower.

IV ketamine is typically not covered by insurance and costs $400–$800 per infusion, or $2,400–$4,800 for an initial 6-session series. Intranasal esketamine (Spravato) is FDA-approved for TRD and covered by many insurance plans.

TMS is covered by most major insurance plans after documented failure of 2+ antidepressants. Out-of-pocket costs vary by plan.

There is no universally "better" treatment between TMS and ketamine. The right choice depends on:

• The severity and acuity of your depression
• Your treatment history
• Your insurance coverage
• Your practical constraints (time, transportation)
• Your personal preferences regarding the treatment experience
• The presence of comorbid conditions (PTSD, suicidality, substance use history)

At Roth Family Medicine and Mental Health, we evaluate each patient individually and discuss all available options — including TMS, ketamine/Spravato, pharmacological augmentation, and functional medicine approaches — to develop a treatment plan that fits your specific situation.

Which has better evidence? Both have strong, comparable evidence bases for TRD. TMS has a longer track record and more total studies; ketamine has more dramatic effect sizes in acute settings and superior anti-suicidal evidence.

Can I try both? Yes. Many patients who don't achieve full remission with one treatment benefit from the other. They work through different mechanisms and are not mutually exclusive.

What if I've already tried TMS and it didn't work? Ketamine is a reasonable next step. The mechanisms are entirely different, and TMS non-response does not predict ketamine non-response.

1. O'Reardon JP, et al. Efficacy and safety of TMS in the acute treatment of MDD. Biol Psychiatry. 2007;62(11):1208–1216.
2. Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–354.
3. Carpenter LL, et al. Transcranial magnetic stimulation (TMS) for major depression. Depress Anxiety. 2012;29(7):587–596.
4. Murrough JW, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression. Am J Psychiatry. 2013;170(10):1134–1142.

Medical Disclaimer: This content is for educational purposes only. Treatment decisions should be made in consultation with a qualified medical provider.

Kyle Roth, FNP-BC, APRN, MSN, MHA | Roth Family Medicine and Mental Health | Pocatello, Idaho | 208-904-4705 | www.rothfamilymed.com