After one or two antidepressants have not worked, both another medication step and TMS are reasonable next moves, and neither is clearly better for everyone. A further medication switch is easier to start and covered almost everywhere, but in the large STAR*D study of medication sequences, the odds of remission fell with each additional step. TMS asks for daily visits over several weeks and has a different, mostly local, side-effect profile; it is supported by major guidelines for depression that has not responded to medication.
The right choice depends on your history, side effects, preferences and practical constraints. This guide lays out what the evidence says and the questions that usually decide it. It is not a verdict.
What the odds look like with another medication
The best-known data come from STAR*D, a large U.S. study that moved people through up to four treatment steps. Remission rates were 36.8% at the first step, 30.6% at the second, 13.7% at the third and 13.0% at the fourth, and the investigators reported a cumulative remission rate of 67%. People who needed more steps also had higher relapse rates afterward.
There is an important caveat. A 2023 reanalysis that stuck more closely to the original study protocol estimated cumulative remission at 35.0% rather than 67%. The original investigators disputed that reanalysis. Either way, the pattern most people take from STAR*D holds: the chance of remission with each new medication step after the second is lower than at the start. The physician's guide covers the debate in after two antidepressants: what STAR*D tells us.
Medication steps are not all switches. They can mean raising a dose, changing to a different class, or adding a second medication (augmentation). Your psychiatrist will consider whether earlier trials were long enough and at a full dose; antidepressants usually take 4 to 8 weeks to work. If you are unsure whether your depression counts as treatment-resistant, see what treatment-resistant depression means and signs your treatment is not working.
What the odds look like with TMS
TMS figures depend heavily on study design, so they need the same care. In the NIMH-funded sham-controlled trial, 14.1% reached remission with active TMS versus 5.1% with sham, and most remitters had relatively low treatment resistance. In a real-world study of 307 patients who had failed an average of 2.5 adequate medication trials, clinician-rated remission was 37.1%, but that study was open-label with no sham group. Canadian guidelines summarize response rates for hard-to-treat depression at 40% to 50%.
These numbers cannot be laid side by side with STAR*D. The studies enrolled different people, used different rating scales and definitions, and STAR*D had no placebo. What can be said is that both paths offer a real, but far from certain, chance of improvement, and that the odds for any single option decline as depression becomes more treatment-resistant.
Side-by-side: another antidepressant vs a TMS course
| Another medication step | A TMS course | |
|---|---|---|
| How it works | A pill that circulates through the whole body | Magnetic pulses to one brain region; nothing circulates afterward |
| Time commitment | A daily pill; usually 4 to 8 weeks to judge the effect | Daily weekday visits; typically 20 to 30 sessions over about 6 weeks |
| Common side effects | Upset stomach, headache, sexual dysfunction, among others | Headache and scalp discomfort, usually mild and easing after the first week |
| Most serious rare risk | Varies by drug; an increase in suicidal thoughts in people under 25 early in treatment | Seizure, under 1 per 60,000 sessions within guidelines in people without risk factors |
| Guideline position after failed medications | Standard next step in most guidelines | First-line for treatment-resistant depression in CANMAT; "weak for" after two or more trials in VA/DoD |
| Access and cost | Widely covered; usually lower out-of-pocket | Often covered with prior authorization; more visits and paperwork |
Side effects: often the deciding factor
Many people reach this decision not because medications failed to help but because they could not tolerate them. Common side effects of SSRIs and other antidepressants include upset stomach, headache and sexual dysfunction, though they are often mild and can ease over time. Canadian guidelines say TMS can be recommended as a first choice when there are tolerability concerns with medication options. The Clinical TMS Society likewise recommends considering TMS when intolerance rules out medications.
TMS side effects are mostly felt at the head during the course: headache and scalp discomfort are the most common, and 4.5% of patients in the pivotal NeuroStar trial stopped because of side effects. If side effects were what drove you off medication, read where TMS fits after antidepressant side effects and TMS side effects.
You may not have to choose: combining TMS and medication
TMS and antidepressants are not either-or. TMS can be given with or without antidepressants, and expert consensus found no evidence that combining them increases side effects; most expert clinicians keep existing medications going during a course. The adolescent clearances specifically require TMS to be added to medication. In a 1-year follow-up of people who responded to TMS while continuing antidepressants, 62.5% kept meeting response criteria.
The evidence on combining has gaps. The same consensus noted there are no controlled-trial data supporting medication use alongside TMS, and APA's 2010 guideline noted that one large sham-controlled trial of TMS added to medication showed no significant benefit. Practical rules are in medications during TMS, and the research is reviewed in combining TMS with medication.
How long the benefit lasts on each path
Getting well is half the question; staying well is the other half. In STAR*D, people who needed more medication steps to reach remission were more likely to relapse during follow-up. That is one reason a later medication step can feel less durable even when it works.
For TMS, a meta-analysis of people who responded to an initial course found that about 53% were still responding at 6 months and about 46% at 12 months. Studies that kept people on antidepressants and reintroduced TMS when needed reported somewhat better numbers, so roughly half to about 6 in 10 initial responders were still doing well at a year. TMS can also be repeated: in a 2026 multisite cohort, 82.5% of people who had responded before responded again to a second course, though that study looked back at records rather than testing it prospectively.
Neither path is a one-time fix. Whatever you choose, it helps to agree in advance with your psychiatrist on what "working" means, how you will track it, and what the plan is if symptoms return. See life after TMS: building a relapse-prevention plan.
Cost and time burden
A medication change usually means a prescription, a copay and follow-up visits every few weeks. TMS means getting to a clinic five days a week for about six weeks, and often a prior authorization before you start. Health plans typically ask for a certain number of failed medication trials before they cover TMS, and the number varies by plan; see how many antidepressants you need to try before TMS is covered and does insurance cover TMS. If you are paying yourself, TMS cost without insurance explains what drives the price.
The time cost is real, but it ends. A TMS course has a finish line; a medication is often taken for months or longer after it works.
Questions that usually decide it
- How many adequate medication trials have you had? One or two well-dosed trials point toward either path; several point more strongly toward non-medication options.
- What happened with side effects? If side effects ended past trials, TMS deserves serious weight.
- Is there an untried medication step with a clear rationale? For example, a different class, or an augmentation strategy your psychiatrist thinks fits your symptoms. If the honest answer is "we would be guessing", that shifts the balance toward trying something different in kind, such as TMS.
- Can you realistically get to daily sessions? Work, childcare and travel time matter. A course you cannot finish is worth less than a simpler plan you can stick with.
- How severe is the depression right now? With psychotic symptoms or acute suicidal thinking, treatments with established efficacy in that situation, such as ECT, should be considered first.
- Do you have a seizure history, bipolar disorder or metal in your head? These need specialist review before TMS.
- What would you choose if both had the same odds? Your preference is a legitimate part of the decision.
If you are thinking about suicide or are in crisis, call or text 988 (the 988 Suicide & Crisis Lifeline) or go to the nearest emergency room.
Other options to keep in view
TMS and another antidepressant are not the only routes. Psychotherapy can be combined with either. Esketamine (Spravato) nasal spray is FDA-approved for treatment-resistant depression and is given in certified clinics with at least 2 hours of monitoring after each dose. Canadian guidelines rate it second-line because of side effects and feasibility. ECT is more effective than TMS overall, especially for psychotic depression, though it requires anesthesia and can affect memory. See TMS vs ketamine therapy, the practice's Spravato page, and how to talk to your provider about changing medications.
For more on whether TMS fits you, see the TMS patient guide and TMS therapy at the practice.
Sources
- 510(k) Summary K231926: NeuroStar Advanced Therapy System. U.S. Food and Drug Administration, 2024. accessdata.fda.gov
- Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Archives of General Psychiatry, 2010. pubmed.ncbi.nlm.nih.gov
- Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and Anxiety, 2012. pubmed.ncbi.nlm.nih.gov
- Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Clinical Neurophysiology, 2019. europepmc.org
- Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems. U.S. Food and Drug Administration, 2011. fda.gov
- Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biological Psychiatry, 2007. pubmed.ncbi.nlm.nih.gov
- Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. Journal of Clinical Psychiatry, 2008. europepmc.org
- Safety Information. Neuronetics (NeuroStar), 2026. neurostar.com
- Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. American Psychiatric Association, 2010. psychiatryonline.org
- Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. Journal of Clinical Psychiatry, 2018. pmc.ncbi.nlm.nih.gov
- Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults. Canadian Journal of Psychiatry, 2024. pmc.ncbi.nlm.nih.gov
- VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder. U.S. Department of Veterans Affairs / Department of Defense, 2022. healthquality.va.gov
- The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimulation, 2016. pmc.ncbi.nlm.nih.gov
- The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacology, 2007. pubmed.ncbi.nlm.nih.gov
- Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a systematic review and meta-analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2014. pubmed.ncbi.nlm.nih.gov
- SPRAVATO (esketamine) nasal spray, CIII: Prescribing Information. Janssen / DailyMed, 2026. dailymed.nlm.nih.gov
- Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry, 2006. pubmed.ncbi.nlm.nih.gov
- A reanalysis of the STAR*D study's patient-level data with fidelity to the original research protocol. BMJ Open, 2023. pubmed.ncbi.nlm.nih.gov
- Durability of antidepressant response to repetitive transcranial magnetic stimulation: Systematic review and meta-analysis. Brain Stimulation, 2019. pubmed.ncbi.nlm.nih.gov
- A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period. Journal of Clinical Psychiatry, 2014. pubmed.ncbi.nlm.nih.gov
- Transcranial Magnetic Stimulation Retreatment for Recurrent Depression: A Large Real-World Multisite Cohort Study. Acta Psychiatrica Scandinavica, 2026. pubmed.ncbi.nlm.nih.gov
- Mental Health Medications. National Institute of Mental Health, 2023. nimh.nih.gov
- The STAR*D Data Remain Strong: Reply to Pigott et al.. American Journal of Psychiatry, 2023. pubmed.ncbi.nlm.nih.gov
FAQs
Is TMS more effective than antidepressants?
There is no good head-to-head answer. TMS and medication studies enrolled different patients and used different measures. Both offer a real but uncertain chance of improvement after earlier treatments have failed.
Can I try TMS before trying a second antidepressant?
FDA labels cover adults whose depression has not improved enough on antidepressant medication in the current episode, but insurance plans often require more failed trials before they pay. Discuss both with your psychiatrist.
Will I be able to stop my antidepressant after TMS?
Possibly, but that is a separate decision made with your prescriber after the course. Stopping too soon or too quickly can cause unpleasant effects, so never stop on your own.
What if I have already tried four or more medications?
In STAR*D, remission rates at the third and fourth steps were much lower than at the first two. That is a strong reason to discuss non-medication options such as TMS, esketamine or ECT.
