When depression does not improve after medication and therapy, it can be frustrating. You may start wondering whether you need a different type of treatment.
Two options you may hear about are TMS and Spravato (esketamine).
Both can be used when standard depression treatments have not provided enough relief. But TMS and Spravato are very different treatments. One uses magnetic stimulation of the brain. The other is a prescription nasal spray that acts on a different brain pathway than most traditional antidepressants.
So, how do you know which option may be right for you?
This guide explains the major differences between TMS and Spravato for treatment-resistant depression, including how they work, what treatment feels like, possible side effects, and questions to discuss with your mental health provider.
Treatment-resistant depression (TRD) generally refers to depression that has not improved enough after adequate treatment with antidepressant medications.
It does not mean your depression cannot be treated.
Instead, it may mean that the treatments you have tried so far have not been the right fit. Your provider may need to reconsider your diagnosis, medications, treatment plan, or other factors that could be affecting your symptoms.
Before recommending another treatment, a mental health provider may review:
When depression continues despite appropriate treatment, options such as TMS or Spravato may be considered.
| TMS | Spravato | |
|---|---|---|
| What is it? | Noninvasive brain stimulation | Prescription esketamine nasal spray |
| Uses medication? | No | Yes |
| How does it work? | Magnetic pulses stimulate brain areas involved in mood | Acts mainly through the brain’s glutamate/NMDA system |
| Where is it given? | Medical office or treatment center | Certified healthcare setting |
| Anesthesia needed? | No | No |
| Typical early schedule | Often 5 days a week for several weeks | Usually twice weekly during the first 4 weeks for TRD |
| Observation afterward? | Usually no extended observation | At least 2 hours |
| Can you drive afterward? | Generally yes | No. You should not drive until the next day after a restful sleep |
| Common concerns | Scalp discomfort, headache | Dizziness, dissociation, nausea, sedation, increased blood pressure |
| FDA-approved for TRD? | TMS devices are FDA-cleared for major depressive disorder under specific indications | Yes, for adults with TRD |
The exact treatment plan can vary based on the device, protocol, diagnosis, medical history, and insurance requirements.
Transcranial magnetic stimulation, or TMS, is a noninvasive treatment that uses magnetic fields to stimulate nerve cells in the brain.
During treatment, an electromagnetic coil is placed against the scalp. The device sends repeated magnetic pulses to areas of the brain involved in mood regulation.
For depression, this is often called repetitive TMS, or rTMS.
Unlike a medication, TMS does not travel through your bloodstream. It also does not require surgery or anesthesia.
You remain awake during treatment.
You may hear clicking from the machine and feel tapping or knocking sensations on your scalp. Some people develop scalp discomfort or headaches, especially early in treatment.
You can usually return to normal activities after a standard TMS session.
A typical course may involve treatment on weekdays for several weeks, although newer TMS protocols can have different schedules.
Spravato is the brand name for esketamine, a prescription nasal spray used for certain forms of depression in adults.
Esketamine is related to ketamine, but Spravato is a specific FDA-approved medication with its own dosing, safety requirements, and treatment program.
One major difference between Spravato and many traditional antidepressants is the pathway it targets.
Many commonly prescribed antidepressants mainly affect serotonin, norepinephrine, or dopamine. Esketamine acts primarily on the brain’s glutamate system, including a receptor called the NMDA receptor.
Glutamate is a chemical messenger involved in communication between brain cells.
This different mechanism is one reason Spravato may be considered when traditional antidepressants have not worked well enough.
Yes.
Spravato is FDA-approved for treatment-resistant depression in adults.
An important update occurred in January 2025: Spravato can now be used for treatment-resistant depression by itself (monotherapy) or together with an oral antidepressant.
You may still find older information online saying that everyone receiving Spravato for treatment-resistant depression must also take an oral antidepressant. That is no longer the current FDA labeling.
Spravato is also approved, together with an oral antidepressant, for depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behavior.
However, Spravato has not been proven to prevent suicide or eliminate the need for hospitalization when hospitalization is clinically necessary.
Spravato is not a prescription you pick up and take home.
You administer the nasal spray yourself under the supervision of a healthcare professional at a Spravato REMS-certified healthcare setting.
REMS stands for Risk Evaluation and Mitigation Strategy. It is an FDA-required safety program for medications with certain serious risks.
Your blood pressure is checked as part of treatment, and you are monitored for at least two hours after each Spravato treatment.
For treatment-resistant depression, the FDA-recommended schedule generally begins with:
Weeks 1–4:
Treatment twice a week.
Weeks 5–8:
Treatment once a week.
Week 9 and after:
Treatment once a week or every two weeks, depending on your response and clinical needs.
Your provider evaluates whether the treatment is helping and whether continued treatment is appropriate.
This is one of the most common questions patients ask.
There is no reliable rule that says one treatment will work faster for every person.
Spravato is often described as a rapid-acting antidepressant treatment because some patients can experience improvement relatively early in treatment. However, response varies, and one treatment session does not tell you whether Spravato will work for you.
TMS usually involves repeated sessions over several weeks before its full benefit can be evaluated.
Recent research comparing TMS and esketamine directly is growing, but there is still not enough high-quality head-to-head evidence to declare one treatment universally better.
The more useful question is often:
Which treatment has the best balance of potential benefit, safety, convenience, and medical suitability for me?
Not necessarily.
Both treatments can help some people with difficult-to-treat depression. Neither treatment works for everyone.
Research directly comparing the two is still developing. Some newer studies suggest that outcomes can differ depending on the patient, treatment protocol, and time point being measured.
That means claims that Spravato is simply “better” than TMS – or that TMS is always better than Spravato – should be viewed cautiously.
Treatment decisions should be individualized.
For many patients, the decision is not only about how the treatments work.
The experience is also very different.
You generally remain alert throughout treatment.
There is no medication causing sedation or dissociation, and anesthesia is not needed. Most patients can leave after treatment and continue their normal activities.
However, TMS often requires frequent office visits over several weeks.
The treatment itself is given as a nasal spray, but your appointment includes a monitoring period.
Spravato can cause dissociation, which is a temporary feeling of being disconnected from yourself, your thoughts, your surroundings, or your sense of time.
It can also cause sedation, dizziness, nausea, increased blood pressure, and other effects.
Because of these risks, you must be monitored for at least two hours after treatment.
You also cannot drive yourself home after Spravato treatment. You should not drive or operate machinery until the next day after a restful sleep.
Transportation therefore becomes an important part of planning treatment.
TMS does not expose the rest of your body to a medication, which can be appealing to people who have struggled with medication side effects.
Common side effects may include:
Serious complications are uncommon, but seizures are a recognized rare risk with TMS.
Your provider should review your medical history and implanted devices before treatment because certain metal or electronic devices in or near the head may affect whether TMS is appropriate.
Spravato has a different safety profile because it is a medication.
Common side effects reported in adults being treated for treatment-resistant depression include:
Spravato carries an FDA boxed warning that includes risks involving sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors in certain younger patients taking antidepressants.
This is one reason treatment must occur in a certified healthcare setting with monitoring.
TMS may be worth discussing if:
TMS is not automatically the better choice because it does not involve medication. Your provider still needs to determine whether it is appropriate for your diagnosis and medical history.
A Spravato evaluation may be worth discussing if:
Spravato is not appropriate for everyone. Certain cardiovascular, cerebrovascular, pregnancy-related, substance-use, and other medical considerations require careful review.
For example, Spravato is contraindicated in people with certain aneurysmal vascular diseases, arteriovenous malformations, a history of intracerebral hemorrhage, or hypersensitivity to esketamine, ketamine, or ingredients in the medication.
This depends on what “convenient” means for you.
TMS can require more frequent trips to a treatment center, often five days per week during an initial course. But standard TMS generally does not require a two-hour observation period or a ride home.
Spravato usually requires fewer treatment days per week, but each visit takes longer because of the required monitoring period. You also need transportation home.
For someone balancing work, childcare, school, or caregiving, these differences can matter.
Often, yes.
Many patients continue antidepressant medication while receiving TMS. Your treatment team decides which medications should be continued or adjusted based on your individual situation.
Never stop an antidepressant suddenly unless the clinician managing your medication tells you how to do so safely.
Not necessarily for treatment-resistant depression.
Under the current FDA labeling, Spravato can be used alone or with an oral antidepressant for adults with treatment-resistant depression.
This is a significant change from the original approval.
For adults with major depressive disorder and acute suicidal thoughts or behavior, Spravato’s FDA-approved use remains in conjunction with an oral antidepressant.
Your psychiatric provider should determine which approach is appropriate for you.
In some situations, a psychiatrist may consider different advanced treatments at different points in a patient’s care.
However, treatment should not be combined, switched, or added simply because depression has not improved quickly.
A clinician should first review:
The goal is not to keep adding treatments. The goal is to build a treatment plan that makes sense for your specific type of depression.
Both TMS and Spravato may be covered by insurance when medical-necessity requirements are met.
However, coverage rules vary.
Your insurance company may require documentation showing that you have tried certain antidepressants, taken them for an adequate amount of time, or completed other treatments before approving TMS or Spravato.
Prior authorization may also be required.
Before starting treatment, ask the treatment center to verify your benefits and explain what your plan requires.
Do not assume that the next step is automatically TMS, Spravato, or another medication.
Persistent depression deserves a careful reassessment.
Your provider may need to ask whether:
Treatment-resistant depression often requires a broader look at the full clinical picture.
If you are comparing these treatments, consider asking:
These questions can help you compare the options based on your health rather than choosing a treatment based only on advertising or online success stories.
There is no single answer.
TMS may appeal to someone who wants a non-medication treatment and wants to avoid sedation or a required ride home.
Spravato may appeal to someone who is an appropriate candidate for esketamine and wants to explore a medication that works through a different pathway than traditional antidepressants.
But convenience alone should not determine treatment.
Your diagnosis, treatment history, other health conditions, medications, safety risks, and personal preferences all matter.
The best next step is a psychiatric evaluation that looks at why your depression has not improved and which treatment options make sense for you.
Wholesome Clinic provides Spravato treatment in Frisco, Texas for appropriate adult patients.
Before treatment begins, our clinical team evaluates your symptoms, previous depression treatments, medical history, medications, and other factors that may affect whether Spravato is a safe and appropriate option.
Spravato treatments take place in a monitored clinical setting according to required safety protocols.
If antidepressants have not provided enough relief and you are wondering whether Spravato may be an option, you can schedule an evaluation with Wholesome Clinic to discuss your treatment history and next steps.
Learn More About Spravato Treatment at Wholesome Clinic
No.
Spravato contains esketamine, which is related to ketamine but is not the same treatment as receiving ketamine.
Spravato is an FDA-approved nasal spray with specific indications, dosing instructions, monitoring requirements, and a required REMS safety program.
No. TMS uses magnetic pulses to stimulate targeted areas of the brain. No medication enters your bloodstream during the treatment.
TMS can cause tapping or uncomfortable sensations on the scalp. Headache and scalp discomfort are among the more common side effects. Many patients find that discomfort improves as they become accustomed to treatment.
Some people experience temporary changes in perception or a feeling of disconnection during treatment. This is called dissociation. Others may experience dizziness, sleepiness, or a feeling described as intoxication.
These effects are one reason patients are monitored after each treatment.
Patients must be monitored for at least two hours after each treatment. Your healthcare provider determines when you are clinically stable and ready to leave.
No.
You should arrange transportation home after treatment. The FDA labeling advises patients not to drive, operate machinery, or perform activities requiring full alertness until the next day after a restful sleep.
Standard TMS does not usually cause sedation, so most patients can return to normal activities, including driving, after treatment unless their clinician gives different instructions.
Some patients may notice improvement relatively early, but response varies. Spravato is given as a structured treatment course, and your provider evaluates your symptoms over time rather than judging the treatment from one dose.
TMS treatment usually occurs repeatedly over several weeks. Some people notice changes earlier than others. Your treatment team should use symptom measures and clinical follow-up to track your response.
There are other approaches to difficult-to-treat depression. Depending on your diagnosis and history, a psychiatric clinician may consider medication changes, augmentation strategies, psychotherapy, electroconvulsive therapy (ECT), or other evidence-based options.
Treatment-resistant depression does not mean there are no treatments left to consider.
DEPRESSION NOT IMPROVING?
If you have tried antidepressants without enough improvement, a psychiatric evaluation can help clarify what may be contributing to your symptoms and which treatment options are appropriate for you.
Wholesome Clinic provides treatment-resistant depression evaluations and Spravato treatment for appropriate adults in Frisco, Texas. We do not currently provide TMS treatment.
This article was developed using current prescribing information, clinical guidance, and peer-reviewed medical research. Medical information is reviewed periodically and may be updated as evidence and regulatory guidance change.
Medical Disclaimer: This article is for educational purposes and does not replace an individual medical or psychiatric evaluation. Treatment recommendations depend on your diagnosis, medical history, medications, symptoms, and other factors. If you are experiencing a mental health emergency or are in immediate danger, seek emergency medical care.
