What Are Ketamine and TMS?
IV ketamine is a medication delivered directly into the bloodstream through an intravenous line. Originally developed as an anesthetic in the 1960s, ketamine has been used off-label for treatment-resistant depression since researchers discovered its rapid antidepressant effects. At Music City Ketamine, each infusion is administered by Marla Peterson, CRNA, a Certified Registered Nurse Anesthetist with over 20 years of anesthesia experience.
TMS (transcranial magnetic stimulation) is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in specific regions of the brain associated with mood regulation. A magnetic coil is placed against the scalp, typically near the forehead, and delivers targeted pulses to the left dorsolateral prefrontal cortex. TMS was cleared by the FDA for treatment-resistant depression in 2008 and does not involve any medication, anesthesia, or sedation.
These are fundamentally different approaches. Ketamine is a pharmacological intervention—a molecule that changes brain chemistry from the inside. TMS is a neuromodulation technique—an external energy source that changes brain activity from the outside. Understanding this distinction helps clarify why they differ in onset, side effects, and treatment experience.
How Do They Work Differently?
Ketamine works systemically through the glutamate system, the brain's primary excitatory neurotransmitter network. It blocks NMDA receptors, which triggers a cascade of downstream effects: increased BDNF (brain-derived neurotrophic factor) production, activation of AMPA receptors, and rapid formation of new synaptic connections. This is why researchers describe ketamine as promoting neuroplasticity—it helps the brain build new neural pathways relatively quickly. The effect is systemic, meaning ketamine reaches the entire brain and body through the bloodstream.
TMS works through localized magnetic stimulation. The magnetic pulses induce small electrical currents in targeted brain tissue, which modulates neuronal activity in the stimulated region and its connected circuits. Repetitive TMS (rTMS) applied to the left dorsolateral prefrontal cortex—an area often underactive in depression—gradually increases excitability in that region over the course of multiple sessions. The effect is more focal, concentrated on specific brain areas rather than the whole system.
In simple terms: ketamine changes the brain's chemistry broadly and quickly, while TMS changes the brain's electrical activity in a targeted area gradually. Both ultimately promote healthier neural function, but through very different pathways.
How Quickly Does Each Treatment Work?
This is one of the most significant practical differences between the two treatments.
Ketamine is known for its rapid onset. Many patients report noticeable improvement within 24 to 72 hours of their first infusion. Research consistently demonstrates that ketamine can produce meaningful symptom reduction within the first few sessions. This speed is particularly important for patients experiencing severe symptoms or acute suicidal ideation, where waiting weeks for a treatment to take effect is not ideal.
Standard TMS follows a more gradual timeline. The traditional rTMS protocol involves daily sessions over 4 to 6 weeks before most patients experience their full therapeutic response. Some improvement may begin around weeks two or three, but the treatment is designed to build cumulative effects over time.
It is worth noting that the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol—an intensive TMS approach developed at Stanford—can produce results in approximately five days by delivering multiple sessions per day with optimized targeting. This accelerated protocol is not widely available yet, but it represents an important development in shortening the TMS timeline.
For patients who need relief quickly, ketamine generally offers a faster initial response. For patients who can invest more time in a gradual treatment course, standard TMS is a reasonable path.
What Does the Research Say About Effectiveness?
A 2025 network meta-analysis compared the three major interventional treatments for treatment-resistant depression: IV ketamine, repetitive TMS (rTMS), and electroconvulsive therapy (ECT). The study pooled data from multiple clinical trials to compare these treatments head to head.
The key findings:
- There were no significant differences in response or remission rates among IV ketamine, rTMS, and ECT
- Ketamine showed more favorable acceptability—fewer patients discontinued treatment due to adverse effects
- All three treatments demonstrated meaningful efficacy for patients who had not responded to standard antidepressants
Research suggests that IV ketamine and TMS are comparably effective for treatment-resistant depression. The differences between them lie primarily in speed of onset, side effect profile, and treatment logistics rather than overall efficacy. — 2025 Network Meta-Analysis
A separate 2025 study published in The Lancet eClinicalMedicine compared esketamine (the nasal spray form) with rTMS, adding further data to the comparison landscape. While esketamine and IV ketamine are different formulations, the study reinforced that both ketamine-based and TMS-based approaches have meaningful roles in treating resistant depression. You can read more about how IV ketamine compares to esketamine.
The bottom line from current research: both treatments work. Neither has clearly emerged as superior in terms of raw efficacy. The decision often comes down to practical factors—how quickly you need relief, your tolerance for side effects, your schedule, and your insurance situation.
What Are the Side Effects of Each?
The side effect profiles of ketamine and TMS are quite different, reflecting their different mechanisms.
TMS side effects are mostly localized and tend to be mild:
- Headache at or near the stimulation site (most common, especially early in treatment)
- Scalp discomfort or tingling during the session
- Occasional lightheadedness
- Rare risk of seizure (estimated at less than 0.1%)
Most TMS side effects diminish over the course of treatment as patients acclimate. There is no sedation involved, and patients can typically drive themselves home and return to normal activities immediately after each session.
Ketamine side effects are systemic but temporary, typically resolving within one to two hours after the infusion:
- Dissociation (a feeling of detachment or altered perception during the session)
- Mild nausea (manageable with anti-nausea medication)
- Temporary increase in blood pressure and heart rate
- Drowsiness or fatigue after the session
- Occasional dizziness
At Music City Ketamine, Marla Peterson, CRNA, monitors your vital signs throughout every infusion and can adjust the dose in real time if side effects become uncomfortable. Patients cannot drive after a ketamine session and need a companion for the ride home. You can read more about the safety profile of ketamine therapy.
The 2025 meta-analysis noted that ketamine's better acceptability rating—meaning fewer treatment discontinuations—suggests that while its side effects are more noticeable during the session, patients generally find them tolerable and temporary.
What Is the Treatment Schedule Like?
The time commitment for each treatment differs substantially.
IV ketamine at Music City Ketamine typically involves an initial series of 6 infusions over 2 to 3 weeks. Each session lasts approximately 40 to 60 minutes, plus recovery time. After the initial series, maintenance infusions are scheduled based on individual response—some patients return every few weeks, others every few months. Learn more about how many sessions you may need.
Standard TMS requires a larger upfront commitment: 5 sessions per week for 4 to 6 weeks, totaling 20 to 30 sessions in the initial course. Each session lasts about 20 to 40 minutes. After the initial course, some patients undergo periodic maintenance sessions, though TMS effects may last longer between treatments than ketamine.
Here is how the schedules compare at a practical level:
- Ketamine: 6 visits over 2–3 weeks, then periodic maintenance
- TMS: 20–30 visits over 4–6 weeks, then periodic maintenance
For patients with demanding work schedules or significant travel requirements, the fewer total visits for ketamine may be more practical. For patients who prefer a treatment with no systemic side effects and no driving restrictions, the daily TMS routine may be easier to incorporate despite the higher number of sessions.
IV Ketamine vs TMS: Side-by-Side Comparison
| Factor | IV Ketamine | TMS |
|---|---|---|
| Mechanism | Glutamate/NMDA receptor modulation (systemic) | Magnetic pulses stimulating targeted brain regions |
| Onset | 24–72 hours | 2–4 weeks (standard); ~5 days (SAINT protocol) |
| Sessions needed | 6 infusions over 2–3 weeks | 20–30 sessions over 4–6 weeks |
| Duration of effects | 1–3 weeks per infusion; maintenance required | May have longer-lasting effects; maintenance varies |
| Side effects | Dissociation, mild nausea, elevated BP (temporary) | Headache, scalp discomfort (localized, mild) |
| Insurance | Generally not covered (off-label use) | Often covered with prior authorization |
| FDA status | Off-label for depression | FDA-cleared for TRD (2008) |
| Provider level | CRNA (anesthesia specialist) at MCK | Psychiatrist, technician, or trained clinician |
| Setting | Clinical infusion suite; one-on-one monitoring | Outpatient clinic; seated in treatment chair |
| Driving after | No—companion required for ride home | Yes—can drive and resume normal activity |
| Cost at MCK | $475 per session | Not offered (see TMS providers) |
Can Ketamine and TMS Be Combined?
This is an emerging area of research that we find particularly interesting.
Because ketamine and TMS work through different mechanisms, researchers have begun investigating whether combining the two could produce enhanced or longer-lasting therapeutic effects. The theory is compelling: ketamine opens a window of heightened neuroplasticity shortly after administration, and delivering TMS during that window may help the brain consolidate and strengthen the new neural patterns more effectively.
Early-stage research suggests this combination approach may offer benefits beyond what either treatment achieves alone. However, combined ketamine-plus-TMS protocols are not yet standard practice, and larger controlled trials are needed before firm conclusions can be drawn.
If you are currently receiving TMS and considering adding ketamine, or vice versa, we encourage you to discuss this with both your TMS provider and our clinical team. Coordination between providers is important when combining interventional treatments.
How Do You Choose Between Them?
We offer ketamine at Music City Ketamine, not TMS. We want to be transparent about that. But we also believe you deserve an honest assessment of your options rather than a pitch for the treatment we happen to provide. Here are the factors that typically guide this decision:
- Speed of need. If you are in acute distress or need relief quickly, ketamine's 24-to-72-hour onset is a meaningful advantage over standard TMS's multi-week timeline.
- Insurance and cost. TMS is FDA-cleared and often covered by insurance. IV ketamine is $475 per session at our clinic and is typically an out-of-pocket expense. If insurance coverage is a deciding factor, TMS may be more accessible. We provide superbills for potential out-of-network reimbursement and offer financing through Advance Care.
- Side effect tolerance. If you prefer a treatment with minimal systemic side effects and no driving restrictions, TMS may be the better fit. If you are comfortable with temporary dissociation and need faster results, ketamine may be more appropriate.
- Schedule constraints. Ketamine requires fewer total visits (6 over 2–3 weeks) compared to TMS (20–30 over 4–6 weeks). If minimizing clinic visits matters, ketamine is more condensed.
- Severity. For patients with severe, treatment-resistant depression—especially those with suicidal ideation—research suggests ketamine's rapid onset may be particularly valuable. TMS is generally better suited for patients who can afford a more gradual treatment timeline.
- Prior treatment history. If you have tried one of these treatments without adequate response, the other may still be effective since they work through entirely different mechanisms.
A consultation is the best starting point. We can review your treatment history, discuss your priorities, and help you evaluate whether ketamine, TMS, or another approach makes the most sense for your situation. If TMS is the better fit for you, we will tell you that.