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Spravato vs. TMS: Comparing Two Treatments for Depression

When standard antidepressants have not provided adequate relief, it can be difficult to know which advanced treatment to explore next. Two of the most prominent FDA-authorized options for treatment-resistant depression are Spravato (esketamine nasal spray) and transcranial magnetic stimulation (TMS). Both represent meaningful advances in psychiatric care, but they work in fundamentally different ways and come with distinct considerations around side effects, time commitment, and patient experience.

This guide from Diamond Edge TMS offers a balanced, evidence-based comparison to help you have an informed conversation with your psychiatrist about which treatment path may be the best fit for your situation.

Key Takeaways

• Both Spravato and TMS are used to treat depression that has not responded to adequate trials of antidepressant medication. Spravato's FDA indication requires treatment-resistant depression; TMS is FDA-cleared for major depressive disorder, with most insurers requiring documentation of prior medication trials for coverage.
• Spravato (esketamine) is a nasal spray derived from ketamine that acts on the glutamate system and requires a two-hour monitored observation period after every dose due to risks of dissociation, sedation, and blood pressure changes.
• TMS therapy is a non-invasive treatment that uses magnetic pulses to stimulate underactive brain regions. It requires no sedation, and patients can drive themselves home and return to normal activities immediately after each session.
• Side effect profiles differ significantly. Spravato carries risks of dissociation, dizziness, nausea, and elevated blood pressure. TMS side effects are generally limited to mild scalp discomfort and occasional headache.
• The right choice depends on your individual circumstances, including your medical history, lifestyle, and treatment goals. A board-certified psychiatrist like Dr. Jerald Block can help you evaluate your options.

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Understanding Treatment-Resistant Depression

Treatment-resistant depression (TRD) is generally defined as major depressive disorder that has not improved sufficiently after at least two adequate trials of antidepressant medications from different pharmacological classes. Each trial must have been at an appropriate dose for an adequate duration, typically six to eight weeks.

Roughly one-third of people with major depression meet criteria for treatment resistance. This does not mean their depression is untreatable. It means that the standard first-line approaches have not been sufficient, and more targeted interventions are warranted. Both Spravato and TMS were developed specifically for this population, and both have demonstrated efficacy in clinical trials when medications alone have fallen short.

If you have been through multiple medication trials without meaningful improvement, the next step is a thorough evaluation with a psychiatrist experienced in advanced treatment options. At Diamond Edge TMS, medication management and TMS therapy work together as part of a comprehensive treatment plan.

What Is Spravato (Esketamine)?

Background and FDA Status

Spravato is the brand name for esketamine, the S-enantiomer of ketamine. It is administered as a nasal spray under medical supervision. Spravato was approved by the FDA in March 2019 for treatment-resistant depression in adults, and in August 2020 it received an additional indication for major depressive disorder with acute suicidal ideation or behavior, in combination with an oral antidepressant.

How Spravato Works

Unlike traditional antidepressants that primarily target the serotonin, norepinephrine, or dopamine systems, esketamine acts on the glutamate system by blocking NMDA receptors. This mechanism is thought to promote rapid synaptogenesis, the formation of new connections between neurons, which may help restore neural pathways disrupted by chronic depression. The glutamatergic mechanism is what distinguishes Spravato from conventional antidepressants and may explain why it can help some patients who have not responded to serotonin- or norepinephrine-based medications.

Administration and Monitoring

Because of its potential for dissociation, sedation, and abuse, Spravato is available only through a restricted distribution system called the Spravato REMS (Risk Evaluation and Mitigation Strategy). Key requirements include:

• Administration must occur in a certified healthcare setting. Patients cannot take Spravato at home.
• A healthcare provider observes the patient for at least two hours after each dose to monitor for sedation, dissociation, and changes in blood pressure.
• Patients cannot drive or operate heavy machinery until the next day after a restful sleep.
• Treatment is typically administered twice per week for the first four weeks (induction phase), then once weekly or once every two weeks during the maintenance phase.

Side Effects of Spravato

According to the FDA prescribing information, the most commonly reported side effects of Spravato include:

• Dissociation: A feeling of detachment from one's body, thoughts, or surroundings. This was reported in approximately 41% of patients in clinical trials and is one of the primary reasons for the mandatory monitoring period.
• Dizziness: Reported in approximately 29% of patients.
• Nausea: Reported in approximately 28% of patients.
• Sedation: Reported in approximately 23% of patients.
• Increased blood pressure: Transient blood pressure elevations occur frequently and require monitoring. Blood pressure is checked before and after each dose.
• Other effects: Vertigo, anxiety, a feeling of being drunk, and hypoesthesia (reduced sense of touch) have also been reported.

Spravato also carries a boxed warning for sedation, dissociation, and the potential for abuse and misuse, given that esketamine is a Schedule III controlled substance.

What Is TMS Therapy?

Background and FDA Clearance

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation therapy. The FDA first cleared TMS for the treatment of major depressive disorder in 2008, and it has since also been cleared for obsessive-compulsive disorder (OCD). TMS therapy at Diamond Edge TMS uses the NeuroStar system, the most widely studied TMS platform with an extensive body of clinical evidence.

How TMS Works

TMS delivers focused magnetic pulses to the left dorsolateral prefrontal cortex, a brain region consistently associated with mood regulation that tends to show reduced activity in people with depression. These magnetic pulses generate small electrical currents that stimulate neurons in the targeted area, gradually normalizing activity in the mood-regulating circuits that have become underactive.

The mechanism is entirely external and non-systemic. TMS does not involve any drugs entering the bloodstream, which means it does not carry the metabolic side effects or drug interactions associated with systemic medications.

Administration and Patient Experience

A standard course of TMS therapy involves:

• Sessions lasting approximately 19 to 37 minutes, depending on the protocol.
• Treatment five days per week for approximately four to six weeks (typically 36 sessions).
• No anesthesia, sedation, or recovery time required.
• Patients remain fully awake and alert throughout the session and can drive themselves to and from appointments.
• Normal activities, including work, can be resumed immediately after each session.

Side Effects of TMS

TMS has a favorable safety profile compared to most depression treatments. The most commonly reported side effects are:

• Scalp discomfort or mild pain at the treatment site: This typically diminishes after the first few sessions as patients acclimate.
• Mild headache: Usually manageable with over-the-counter pain relievers.
• Lightheadedness: Infrequent and transient.

There is a very small risk of seizure (less than 0.1% of patients in clinical trials). TMS does not cause the dissociation, sedation, nausea, or blood pressure changes associated with Spravato. It is not a controlled substance and carries no risk of abuse or dependence.

Side-by-Side Comparison

Which Treatment Might Be Right for You?

There is no single correct answer for everyone, and both Spravato and TMS have helped patients who were struggling with treatment-resistant depression. The right choice depends on your specific clinical picture, lifestyle, and treatment priorities. Here are some factors to consider:

TMS May Be a Strong Fit If You:

• Want a non-drug, non-invasive approach that does not introduce additional substances into your system.
• Prefer to avoid sedation and the need for someone to drive you home after treatment.
• Need to maintain your normal work and daily schedule during treatment, since sessions are brief and require no recovery time.
• Are looking for a treatment course with a defined endpoint rather than an indefinite maintenance schedule.
• Have concerns about dissociative side effects or a personal or family history of substance use disorders.
• Want a treatment with a well-established long-term safety profile and no risk of dependence.

Spravato May Be Worth Discussing If You:

• Are experiencing major depressive disorder with acute suicidal ideation, as Spravato carries a specific FDA indication for this clinical scenario.
• Have rapid-onset needs, as some patients report mood improvement within hours to days of the first dose.
• Have tried TMS previously without adequate response and are looking for an alternative mechanism of action.
• Have access to a REMS-certified provider and can accommodate the two-hour monitoring requirement and driving restrictions.

Combination and Sequential Approaches

It is worth noting that these treatments are not mutually exclusive. Some patients may benefit from TMS as a first-line advanced intervention and, if needed, discuss Spravato with their provider at a later stage. Others may find that TMS provides a strong foundation that can be supplemented with ongoing medication management. The goal is always to find the combination of approaches that gives you the most sustained relief with the fewest burdens.

Questions to Ask Your Doctor

If you are considering Spravato or TMS for treatment-resistant depression, here are questions that can help guide a productive conversation with your psychiatrist:

1. Do I meet the clinical criteria for treatment-resistant depression? Confirm that you have had adequate trials (appropriate dose and duration) of at least two different antidepressant classes.
2. Based on my medical history and current medications, which treatment carries fewer risks for me? Certain conditions, such as uncontrolled hypertension, aneurysmal vascular disease, or a history of substance use disorders, may influence which option is safer.
3. What does the time commitment look like for each option? Consider not just session length but also travel time, monitoring periods, and how long the full treatment course lasts.
4. What are the expected outcomes, and how will we measure progress? Ask about response rates, remission rates, and how quickly you might expect to notice improvement.
5. What happens after the initial treatment course? Understand whether maintenance sessions or ongoing prescriptions are needed and what a long-term plan looks like.
6. What does my insurance cover? Both treatments typically require prior authorization. Check your insurance coverage before beginning treatment to understand your financial responsibility.
7. Can I continue my current medications during treatment? Both treatments are generally used alongside existing antidepressant regimens, but your doctor should review potential interactions.

Frequently Asked Questions

Can I receive both Spravato and TMS?

In some cases, yes. These treatments use different mechanisms of action and are not contraindicated together. However, combining them requires careful coordination with your psychiatrist. Many patients begin with one treatment and consider adding or switching to the other based on their response.

Does Diamond Edge TMS offer Spravato?

No. Diamond Edge TMS specializes in TMS therapy and medication management. We provide this comparison so that patients exploring their options can make informed decisions. If you and your doctor determine that Spravato is the right path, we can still support your care through medication management and psychiatric consultation.

How long do the effects of each treatment last?

TMS outcomes have been shown to be durable, with many patients maintaining improvement for 12 months or longer after completing a standard course. If symptoms begin to return, retreatment with TMS is an option. Spravato typically requires ongoing maintenance sessions (weekly or biweekly) to sustain its effects, though the frequency may decrease over time.

Is TMS covered by TRICARE?

Yes. TRICARE covers TMS therapy for treatment-resistant depression when clinical criteria are met. Diamond Edge TMS has extensive experience working with TRICARE and military families. Visit our TRICARE coverage page for more details.

What if I have tried both Spravato and TMS without success?

Treatment-resistant depression sometimes requires a multi-faceted approach. If both treatments have been tried, your psychiatrist may recommend adjustments to your medication regimen, psychotherapy approaches, or other emerging treatments. A comprehensive evaluation with an experienced provider like Dr. Block can help identify additional options.

Are there any conditions that would prevent me from receiving TMS?

TMS is not recommended for individuals with metallic implants in or near the head (excluding standard dental work) or implanted magnetic-sensitive medical devices such as cochlear implants or deep brain stimulators. A thorough screening before treatment ensures TMS is safe for you.

Ready to take the next step?

Diamond Edge TMS is accepting new patients in Vancouver, WA.

Request an appointment or call (360) 838-3654.