TMS vs. Ketamine for Treatment-Resistant Depression: What’s the Difference?
When antidepressants haven’t provided enough relief from depression, the next step isn’t always another medication.
Two options that increasingly come up for people with treatment-resistant depression are transcranial magnetic stimulation (TMS) and ketamine. Both represent a different approach from traditional antidepressants, and both may be considered when previous treatments haven’t worked well enough.
But they are very different treatments.
One uses magnetic stimulation to target areas of the brain involved in depression. The other is a medication that affects the brain’s glutamate system and can temporarily change perception and awareness.
So how do TMS and ketamine compare—and what should you know if you’re considering your next treatment option?
First, What Does “Treatment-Resistant Depression” Mean?
Depression is often considered treatment-resistant when symptoms haven’t improved adequately after trials of at least two antidepressants. That doesn’t mean depression is untreatable.
It means the treatments you’ve tried so far haven’t produced the response you and your provider were hoping for—and it may be time to consider a different approach.
For some people, that could mean adjusting medication or combining medications. For others, it may mean considering treatments such as TMS, ketamine or esketamine, or other interventions depending on their symptoms and medical history.
What Is TMS?
Transcranial magnetic stimulation (TMS) is a noninvasive treatment that uses repeated magnetic pulses to stimulate specific neural circuits in the brain. During treatment, an electromagnetic coil is placed against the scalp. You remain awake while the device delivers magnetic pulses to a targeted area of the brain associated with mood regulation.
TMS does not require surgery or anesthesia, and nothing enters your bloodstream. The FDA first cleared an rTMS device for depression in 2008 for people who had not responded adequately to antidepressant treatment.
Treatment is generally delivered through a series of sessions over several weeks rather than as a single procedure.
What Do We Mean by “Ketamine”?
This is where the terminology can get confusing. When people talk about ketamine therapy for depression, they may be referring to more than one treatment.
IV ketamine is ketamine administered intravenously at doses used for psychiatric treatment. Ketamine itself is FDA-approved as an anesthetic, but it is not FDA-approved for the treatment of depression or other psychiatric disorders. When clinicians use IV ketamine to treat depression, they are prescribing it off-label.
Esketamine, sold under the brand name Spravato, is derived from ketamine and is administered as a nasal spray in a supervised healthcare setting. It is FDA-approved for adults with treatment-resistant depression.
For simplicity, we’ll use “ketamine” broadly in this article, but it’s important to ask a provider exactly which form they offer because the treatment experience, regulatory requirements, cost, and insurance coverage can differ.
TMS vs. Ketamine: The Biggest Difference
The simplest distinction is this: TMS is a non-medication brain stimulation treatment. Ketamine is a medication treatment.
With TMS, magnetic pulses repeatedly stimulate targeted neural circuits over a course of treatment.
Ketamine and esketamine work through a different pathway than traditional antidepressants, interacting with the brain's glutamate system. One of the characteristics that has made these medications particularly interesting in depression treatment is how rapidly an antidepressant effect may occur for some patients. NIMH notes that esketamine can sometimes relieve symptoms within hours.
TMS generally works more gradually. Improvement may emerge over the course of several weeks of treatment rather than immediately after an individual session. Neither timeline guarantees that someone will respond.
What Does Treatment Feel Like?
The experience is quite different.
During TMS
You sit awake in a treatment chair while a magnetic coil rests against your head. As the magnetic pulses are delivered, you typically hear clicking and feel tapping against the scalp. You remain alert throughout treatment.
There is no sedation or altered state associated with the treatment itself, and patients can generally return to normal activities afterward.
During Ketamine or Esketamine Treatment
Ketamine can temporarily affect perception, awareness, coordination, and how you experience your surroundings. With esketamine specifically, possible effects include sedation and dissociation.
Because of these risks, Spravato must be administered in a certified medical setting where patients are monitored for at least two hours after treatment. IV ketamine treatment protocols vary between providers, but it also requires medical supervision.
That means a ketamine treatment day can involve more recovery and logistical planning than a TMS session.
How Quickly Can They Work?
This is one of the most significant practical differences.
Ketamine may act rapidly. Research into ketamine has focused in part on its ability to produce antidepressant effects much faster than traditional antidepressants, sometimes within hours or days.
TMS tends to be more gradual. Treatment typically occurs repeatedly over a number of weeks, and symptom improvement may develop as the treatment course progresses.
That doesn't automatically make one approach preferable.
A faster initial response and the longer-term treatment strategy are two different considerations. Your provider may look at the severity and urgency of your symptoms, your previous treatment history, medical considerations, side effects, and what type of ongoing treatment feels realistic for you.
How Do the Side Effects Compare?
Because TMS and ketamine work so differently, their side-effect profiles are different as well.
Common TMS Side Effects
Common side effects of TMS are generally related to the treatment area and may include:
Scalp discomfort
Headache
Tingling
Facial muscle twitching
Lightheadedness
These effects are generally mild to moderate and often improve shortly after treatment. Serious side effects such as seizures are uncommon.
Ketamine and Esketamine Side Effects
Ketamine-based treatment can affect the body and perception more broadly. With esketamine, risks include sedation, dissociation, temporary increases in blood pressure, respiratory depression, and the potential for abuse or misuse. These risks are among the reasons Spravato is administered through a restricted FDA safety program and requires monitoring following treatment. Your individual medical history matters with either treatment, which is why an evaluation with an appropriately trained provider is essential.
What About the Time Commitment?
Both treatments involve more than a single appointment, but the commitment looks different.
TMS typically involves frequent appointments during a defined treatment course. Individual visits can fit relatively easily into a normal day because patients generally don't require sedation or post-treatment observation.
Ketamine or esketamine treatments may happen less frequently, depending on the protocol, but each visit can require more time because of administration, monitoring, and recovery.
For patients considering treatment in Santa Fe or traveling from Albuquerque and elsewhere in New Mexico, that practical difference matters.
It’s worth asking yourself not only, “Which treatment interests me?” but also: Which treatment schedule can I realistically complete? Consistency matters with either approach.
Do You Have to Stop Your Antidepressant?
Not necessarily.
TMS is often used alongside existing depression treatment, which may include medication and psychotherapy. Your prescribing clinician determines whether any medication changes are appropriate.
Ketamine treatment also doesn’t automatically mean stopping other antidepressants. The exact medication plan depends on whether you are receiving IV ketamine or esketamine and on your individual clinical situation.
Never change or discontinue an antidepressant without discussing it with the clinician managing your medication.
Is TMS or Ketamine “Better” for Depression?
There isn’t one answer that applies to everyone. These aren't simply two versions of the same treatment.
They differ in how they are delivered, how quickly improvement may emerge, side effects, treatment-day experience, medical considerations, and what ongoing care can look like.
A person who wants to avoid another medication may be particularly interested in the non-medication nature of TMS.
Someone whose clinical circumstances make the possibility of rapid symptom improvement especially important may have a conversation with their psychiatrist about ketamine or esketamine.
And sometimes the question isn’t TMS or ketamine forever. Depression treatment can evolve over time, and different interventions may have different roles in someone's larger treatment plan.
The right question is less “Which treatment wins?” and more: Given my symptoms, treatment history, health, priorities, and life circumstances, which approach makes the most sense to consider next?
Questions to Ask When Comparing TMS and Ketamine
If you’re considering either treatment, bring questions to your provider.
Ask what form of treatment they are recommending and why. Ask what evidence supports it for your particular diagnosis, what side effects to expect, how often you’ll need treatment, whether you'll need someone to drive you home, what medications you can continue, how progress will be measured, and what happens if you respond—or if you don't.
You should understand not only what the treatment is, but what the entire treatment experience will ask of you.
Exploring TMS in Santa Fe
If you’ve already tried multiple treatments for depression and still don’t feel like yourself, you have not necessarily reached the end of your options.
At Anew TMS in Santa Fe, we help patients explore whether TMS may be an appropriate next step for treatment-resistant depression.
That begins with understanding where you are now: what you’ve tried, what helped, what didn’t, and what you want your life to look like if treatment begins working.
If you're comparing TMS with ketamine, another medication, or simply another antidepressant trial, you don't need to have already made that decision before talking with us.
Or see Your Patient Journey to understand what TMS treatment at Anew looks like from the initial consultation through your full course of care.
When you're ready, [schedule a consultation with Anew TMS] to talk about whether TMS belongs among the options you're considering.