TMS vs Esketamine

• TMS and esketamine are both FDA-approved to treat treatment-resistant depression.
• TMS uses magnetic stimulation; esketamine is a nasal medication.
• Esketamine often acts faster; TMS builds gradually.
• Side effects of both treatments are manageable for most patients.
• Insurance coverage varies but is becoming more standardized.

Roughly 40% of people respond to traditional oral antidepressants. What about the other 60%? For those who are struggling with depression and don’t respond to medications, two FDA-approved options demonstrate robust patient outcomes in the U.S.: transcranial magnetic stimulation (TMS) and esketamine (Spravato®). Both treatments are different in how they work, how they feel, and how they fit into daily life.

This guide compares TMS and esketamine to help you choose the option that best fits your needs and circumstances.

TMS is a non-invasive treatment that utilizes targeted magnetic pulses to stimulate parts of the brain responsible for mood regulation, typically the left dorsolateral prefrontal cortex, which is often underactive in depression.

Treatment occurs at an outpatient clinic. A magnetic coil is gently placed atop the scalp to deliver brief pulses that stimulate neural activity. No sedation or anesthesia is needed, and patients remain awake and alert throughout each session.

In the U.S., TMS is also FDA-approved for treating obsessive-compulsive disorder (OCD) and is often used for related conditions, such as anxiety symptoms that accompany depression.

Esketamine is a nasal spray treatment derived from ketamine that is marketed as Spravato®. Unlike typical antidepressants that primarily act on serotonin, dopamine, or norepinephrine, esketamine works by targeting the glutamate pathways in the brain. It’s fast-acting and FDA-approved for treatment-resistant depression, and it can serve as stand-alone therapy for some patients.

Treatment occurs in a certified medical setting. Patients use the nasal spray and remain at the clinic for observation, ensuring safety and allowing clinicians to monitor responses.

Both treatments promote neuroplasticity, but in different ways.

TMS uses external magnetic stimulation over repeated sessions to support healthier communication between neural connections in underactive brain regions associated with mood, motivation, and executive functioning.

Esketamine works by modulating NMDA receptors and glutamate signaling. It blocks NMDA receptors, which increases overall glutamate in the brain. This promotes rapid changes in synaptic connectivity, which helps explain why some patients experience symptom relief within hours or days.

These distinct mechanisms account for the varying response patterns and why clinicians may consider both options over the course of treatment.

Esketamine is touted for its rapid effects; many patients report noticeable mood shifts as early as after their initial treatment or first few treatments. This can feel especially significant for patients suffering from severe depressive episodes.

TMS is a cumulative treatment and follows a more gradual trajectory. Patients begin to notice clinical improvements after several weeks of consistent treatment.

Neither timeline is inherently “better.” It ultimately comes down to patient preference and how each treatment fits into their daily routines.

Both treatments maintain strong safety records when delivered under proper clinical supervision.

With TMS, patients may experience mild scalp discomfort or brief headaches during initial sessions, but eventually become acclimated to the pulses. A great benefit of TMS treatment is that it does not produce systemic effects that traditional antidepressants often come with.

Esketamine can temporarily cause mild dissociation, dizziness, and sedation on treatment days. They typically go away within hours, and patients are in a monitored environment optimized for comfort and support.

For both treatments, these side effects are manageable and short-lived.

TMS follows a structured schedule. A typical depression protocol for TMS is 36 treatments, where patients ideally go in for treatments five sessions per week for the first 30 sessions, then enter a taper phase of every other day for the remaining 6 sessions over the course of four to six weeks. Each session lasts roughly 20 to 40 minutes and requires no downtime, meaning patients can resume their daily activities immediately afterward.

Esketamine follows a phased model. Patients start on a standard induction phase of two sessions per week for 4 weeks, followed by weekly or biweekly maintenance sessions. Each visit is typically 2 hours to 2 ½ hours to allow for clinical observation. Patients cannot drive or operate any heavy machinery for their treatments and must arrange transportation.

The right choice usually depends on lifestyle factors such as work flexibility, transportation access, and personal tolerance for time in clinical settings.

Most major insurance plans, including Medicare and many state Medicaid programs, cover TMS for treatment-resistant depression as long as patients meet specific medical criteria, namely that they’ve tried more than two antidepressants with no medical contraindications. Prior authorization is commonly needed, but coverage is becoming increasingly standardized.

Most major insurance plans, including Medicare and many state Medicaid programs, also cover esketamine. Due to medication and monitoring requirements, additional approvals may be required.

Out-of-pocket costs for both treatments vary by insurance plan and provider. Most clinics offer insurance navigation support to help patients explore their options and provide estimated patient responsibility before treatment begins.

TMS patients often experience clinical benefits for months to several years after completing a full course of treatment. Some patients return for additional courses or maintenance sessions if their depressive symptoms come back. Esketamine requires an ongoing dosing schedule to maintain benefit; patients continue maintenance sessions for several months to years.

Both treatments ultimately offer long-lasting benefits for many patients. Multiple factors influence long-term outcomes such as individual biology, treatment adherence, and supportive care such as therapy or lifestyle changes.

TMS clinics have become widely available across the U.S., especially in urban and suburban areas. Established treatment protocols, specialized machines, and equipment support care.

Esketamine requires treatment centers to be certified under the FDA Risk Evaluation and Mitigation Strategy (REMS) standards. Treatment centers are becoming more available, though access may be more limited in some regions of the country. Geography, clinic density, and referral pathways all influence how easy it is to access treatments.

Several considerations often guide decision-making:

• Preference: Medication-based vs. non-medication treatment.
• Urgency: Need for rapid symptom relief.
• Comfort: With altered states vs. external stimulation.
• Logistics: Scheduling flexibility and transportation access.
• Cost: Insurance coverage and financial considerations.

A clinician experienced with both therapies can help weigh these factors in context to determine the best fit for you.

Clinical studies support both treatments as effective options for treatment-resistant depression.

TMS shows remission rates that commonly range from 30% to 60%, depending on the protocol and patient characteristics.

Esketamine, similarly to ketamine infusions, demonstrates strong response rates as well, particularly for individuals who do not respond to conventional antidepressants.

Neither therapy guarantees success, but both expand evidence-based options beyond traditional medication alone.

TMS sessions are structured and predictable. During treatment sessions, patients often watch television, read, listen to music, or rest. The treatment integrates easily into daily life with no downtime required.

Esketamine sessions feel more inward-focused. Some patients describe a dreamlike or reflective state during treatment, followed by a sense of emotional reset.

Neither experience fits everyone. Personal comfort plays a meaningful role in satisfaction and adherence.

TMS and esketamine can be done together or sequentially since their mechanisms of action complement each other. Esketamine can support rapid stabilization, whereas TMS can reinforce longer-term neural changes. Treatment plans remain individualized and clinician-guided.