Spravato or TMS for Treatment-Resistant Depression? A New Haven Guide to Choosing the Right Treatment

If you have tried antidepressants, therapy, or both and still feel trapped in depression, you may be asking an exhausting question: What comes next?

Treatment-resistant depression is not a personal failure. It may mean that your depression is not responding adequately to the treatment pathway you have tried: not that recovery is impossible. Today, several evidence-based depression treatment options can be considered, including Spravato treatment, transcranial magnetic stimulation (TMS), medication management, and psychotherapy.

This guide compares these options so you can have a more informed conversation with a qualified provider. At Light-tunnel Behavioral Health Services Inc. in New Haven, care is personalized to your symptoms, treatment history, medical conditions, preferences, and goals. Dr. Omolola Aragbada, PMHNP, is one of the psychiatric providers at Light-tunnel Behavioral Health Services Inc. who supports personalized care, and the practice provides psychiatric evaluation, medication management, therapy, TMS, and esketamine/Spravato services.

What Is Treatment-Resistant Depression?

Treatment-resistant depression, commonly abbreviated TRD, generally refers to major depressive disorder that has not improved adequately after two appropriate antidepressant trials at therapeutic doses and for sufficient durations. Definitions can vary, so your psychiatric provider will review your actual medication history carefully.

Before concluding that depression is treatment-resistant, your clinician may also assess:

• Whether medications were taken consistently and at an adequate dose
• Side effects that limited treatment
• Bipolar disorder, ADHD, OCD, trauma, substance use, or anxiety
• Sleep disorders, thyroid disease, chronic pain, or other medical contributors
• Whether psychotherapy was appropriately matched to your needs
• Current suicidal thoughts, psychosis, mania, or other urgent symptoms

Depression can feel like a mechanical gear that has become stuck. Increasing the same medication may not always unstick the system. Sometimes your care plan needs a different mechanism: such as glutamate-based treatment with esketamine or network-based neuromodulation with TMS.

Spravato Treatment: When Speed and a Different Mechanism Matter

Spravato is the brand name for esketamine nasal spray. Esketamine is a noncompetitive NMDA receptor antagonist that acts on the glutamate system rather than primarily targeting serotonin or norepinephrine.

Glutamate is one of the brain’s main excitatory neurotransmitters. A useful metaphor is to think of the brain as a communication network whose roads have become damaged or underused during a prolonged depressive episode. Esketamine may help temporarily open alternative routes and support synaptic plasticity: the brain’s ability to adapt and form or strengthen connections.

The precise antidepressant mechanism is complex and not completely understood. However, randomized controlled trials have found that intranasal esketamine can reduce depressive symptoms in adults with TRD, including when added to a newly initiated oral antidepressant [1].

What a Spravato session typically involves

For TRD, the FDA-approved schedule generally begins with:

• Twice-weekly treatment during weeks 1–4
• Weekly treatment during weeks 5–8
• Weekly or every-other-week treatment thereafter, depending on response and tolerability

Spravato must be administered under direct supervision in a certified healthcare setting. You remain under observation for at least two hours after each treatment while the team monitors your blood pressure, breathing, sedation, dissociation, and overall stability [2].

Common effects may include:

• Dissociation or feeling disconnected from yourself or your surroundings
• Dizziness or vertigo
• Sedation or sleepiness
• Nausea or vomiting
• Temporary blood-pressure elevation
• Anxiety, lethargy, or a “floating” sensation

You must arrange transportation home and should not drive, operate machinery, or perform activities requiring full alertness until the next day after a restful sleep.

Spravato may be worth discussing when:

• You have had inadequate responses to appropriate antidepressant trials
• You and your provider are seeking a potentially faster-acting option
• You can attend monitored treatment sessions consistently
• Your cardiovascular and neurological history has been carefully reviewed
• You understand and accept the possibility of transient dissociation and sedation

Spravato is not appropriate for everyone. Your provider must consider conditions such as certain vascular disorders, a history of intracerebral hemorrhage, uncontrolled medical risks, substance-use history, pregnancy, and medication interactions.

TMS Therapy: A Nonmedication Approach to Brain Networks

TMS uses magnetic pulses to stimulate targeted areas of the brain involved in mood regulation. Unlike Spravato, it does not introduce a psychoactive medication into your bloodstream.

A TMS session usually involves sitting in a comfortable chair while a treatment coil rests near your scalp. The magnetic pulses produce electrical activity in targeted cortical networks. You remain awake, and most patients return to normal activities shortly after treatment.

BrainsWay is one of the most researched TMS systems. Its H-coil deep TMS was evaluated in a multicenter, double-blind, sham-controlled randomized trial involving adults with depression who had not responded adequately to antidepressants. In that study, active deep TMS produced greater improvement in depressive symptoms than sham treatment, with higher response and remission rates at the primary endpoint [3].

Potential advantages of TMS include:

• No sedation or dissociation
• No required two-hour post-treatment observation
• No need for a driver after routine sessions
• Limited systemic medication exposure
• The ability to continue many existing medications under medical supervision
• A generally favorable tolerability profile

Possible side effects include scalp discomfort, facial muscle movement, and headache. Seizures are rare but represent an important safety consideration, particularly when risk factors are present.

TMS may be especially appealing if you:

• Prefer a nonmedication treatment
• Need to remain alert after appointments
• Have concerns about medication side effects
• Want a localized treatment that works through brain-network stimulation
• Can attend frequent sessions over several weeks

Read more about TMS therapy for treatment-resistant depression and OCD.

How Do Spravato, TMS, and Medication Management Compare?

There is no universal winner. A 2025 analysis using individual participant data from two separate clinical trials found that both rTMS and intranasal esketamine were more effective than starting a new antidepressant alone after four weeks. rTMS showed a numerically greater symptom reduction than esketamine, but the comparison was not a direct head-to-head randomized trial and was not statistically definitive [4].

That distinction matters. The available evidence does not prove that Spravato is always better than TMS: or that TMS is always better than Spravato. Your treatment history and safety profile are more important than choosing the treatment that sounds newest.

A Practical Decision Guide

During an evaluation, ask yourself and your provider:

1. How quickly do you need meaningful symptom relief?

If your depression is severe and rapidly worsening, your clinician may discuss interventions designed for a faster onset. However, severe suicidal risk may require emergency evaluation or hospitalization: not simply an outpatient Spravato appointment.

2. How do you feel about temporary altered sensations?

If the possibility of dissociation or sedation feels frightening, TMS may feel more comfortable. If you are open to a monitored medication experience, Spravato may remain an option.

3. Do you have medical conditions that affect eligibility?

Blood pressure, cardiovascular disease, neurological history, pregnancy, substance-use history, and current medications can influence whether Spravato or TMS is safer for you.

4. Can you follow the treatment schedule?

Spravato requires monitored appointments and transportation. TMS commonly requires frequent visits over several weeks. The best treatment is one you can safely and consistently complete.

5. What has helped: even partially: in the past?

A partial response can provide valuable information. Your provider may recommend continuing an effective medication while adding TMS, therapy, or another intervention rather than replacing everything at once.

What to Do: and What to Avoid

Do:

• Bring a complete list of prior medications, doses, durations, and side effects.
• Tell your provider about substance use, pregnancy plans, blood-pressure concerns, and neurological conditions.
• Continue psychotherapy and healthy routines as part of comprehensive care.
• Report worsening depression, agitation, mania, unusual behavior, or suicidal thoughts promptly.
• Ask about insurance coverage, transportation, visit frequency, and maintenance planning.

Avoid:

• Stopping antidepressants or mood stabilizers abruptly without medical guidance.
• Using alcohol, recreational drugs, or unapproved sedatives around Spravato treatment.
• Driving after Spravato treatment.
• Assuming a social-media testimonial predicts your response.
• Delaying emergency care because you have an upcoming treatment appointment.

At Light-tunnel Behavioral Health Services Inc., the goal is not to force you into one option. The goal is to understand your depression and build a treatment plan that is compassionate, medically responsible, and specific to you. You can explore the practice’s behavioral health services or contact the New Haven office to request an evaluation.

Medical Safety Disclaimer and Crisis Resources

This article is for educational purposes only. It does not diagnose depression, establish a provider-patient relationship, or replace an evaluation by a qualified healthcare professional. Spravato is a prescription medication with important risks, contraindications, monitoring requirements, and potential for misuse. The FDA label states that Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior, and it does not replace hospitalization when hospitalization is clinically needed [2].

If you may hurt yourself or someone else, cannot stay safe, or are experiencing an acute psychiatric or medical emergency:

• Call or text 988 for the Suicide & Crisis Lifeline in the United States.
• Call 911 or go to the nearest emergency department.
• Do not wait for a routine appointment or attempt to manage an emergency alone.

References

1. Popova V, Daly EJ, Trivedi M, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. American Journal of Psychiatry. 2019;176(6):428–438. PubMed

2. U.S. Food and Drug Administration. SPRAVATO (esketamine) nasal spray: Full Prescribing Information. Revised January 2025. FDA prescribing information

3. Levkovitz Y, Isserles M, Padberg F, et al. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Major Depression: A Prospective Multicenter Randomized Controlled Trial. World Psychiatry. 2015;14(1):64–73. Full article

4. Kaster TS, Dai Y, Vila-Rodriguez F, et al. Efficacy of Intranasal Esketamine Versus rTMS for Treatment-Resistant Depression: Analysis of Individual Participant Data From Two Clinical Trials. eClinicalMedicine. 2025;90:103609. Full article

Next Post in the Series

Continue reading: Breaking the Loop: How OCD Therapy and TMS Can Help You Regain Control