TMS for Bipolar Depression: Evidence and Precautions

TMS is not FDA-cleared for bipolar depression. Every current depression label is for major depressive disorder, and FDA's guidance for TMS devices lists bipolar disorder among the conditions where evidence of safety and efficacy is lacking. Using TMS for the depressive phase of bipolar disorder is therefore off-label, and major insurers classify it as experimental or unproven.

The research is real but mixed. Pooled across 17 sham-controlled trials, TMS shows a small antidepressant effect in bipolar depression, yet most of the individual trials were negative. The feared complication, a switch into mania or hypomania, has occurred at low rates similar to sham. This article goes through the trials, the switch data, the role of mood-stabilizing medication, and who might reasonably consider it.

Why bipolar depression is a separate question

Bipolar depression can look identical to unipolar depression in the room, but it is treated differently. The CANMAT and ISBD bipolar guidelines recommend quetiapine, lurasidone, lithium and lamotrigine among first-line options for bipolar I depression and state that antidepressant monotherapy should not be used for it. Any treatment that lifts mood raises the same concern as antidepressants do: that it might push mood past normal into hypomania or mania.

It also matters because bipolar disorder is often missed. A person referred for TMS after several failed antidepressants may have an unrecognized bipolar illness, which is one reason a careful diagnostic review comes first; see ruling out other causes of apparent treatment resistance and the site's guide to telling bipolar disorder from depression.

What the trials show

The pooled picture

Two meta-analyses published in 2026 reached different-sounding conclusions from overlapping data.

• A meta-analysis restricted to randomized sham-controlled trials (17 trials, 563 patients) found that TMS reduced depressive symptoms more than sham, with a small effect size of 0.34, and improved response and remission rates. But 88.2% of the individual comparisons did not show TMS beating sham, and the pooled effect did not hold up consistently in sensitivity and subgroup analyses. The trials were small, averaging about 15 patients per arm.
• A broader review of 56 articles covering 1,709 patients, including uncontrolled studies, reported an effect size of 0.40 against sham in the randomized trials and, across all active treatment arms, response in 46.81% and remission in 28.25%, figures it described as similar to those in unipolar depression.

The fair reading is a modest average benefit resting on many small studies. The authors of the first analysis concluded that their subgroup findings did not support TMS as an efficacious treatment for bipolar depression at current doses and called for larger trials with higher-dose protocols.

The individual trials worth knowing

These three trials illustrate the problem. The same stimulation pattern, intermittent theta burst, failed outright in one trial when given once daily and produced a large effect in another when given ten times a day with imaging-guided targeting. Whether dose, targeting, patient selection or chance explains the difference is not known, and the positive trial enrolled 24 people at a single center. A 2025 meta-analysis of theta burst trials in bipolar depression (7 trials, 168 participants) found an advantage over sham for symptom reduction and response but not for remission.

For background on the protocols themselves, see theta burst stimulation, accelerated TMS and deep TMS vs standard TMS. The company behind the SAINT protocol has said that bipolar depression is among the indications still in trials and not FDA-cleared.

Mania and hypomania: the switch data

Treatment-emergent mania is the main safety question, and the numbers are more reassuring than many expect.

• An early pooled analysis of 10 randomized trials found treatment-emergent mania in 0.84% of patients given active rTMS and 0.73% given sham, not a significant difference. Of 13 published cases, most were in people with bipolar disorder and most were taking other medication at the time; all resolved with management.
• A 2021 meta-analysis of 25 blinded trials (576 active, 487 sham) found no significant difference in the risk of a hypomanic or manic switch.
• The 2026 review of bipolar depression studies found switch rates low and equivalent to sham, with an odds ratio of 1.3 and a confidence interval running from 0.7 to 2.4.

Low is not zero. In the futility-stopped iTBS trial, one participant developed hypomania during active treatment and a second during the open-label phase. Switches are reported in unipolar depression trials as well: in the 255-patient BRIGhTMIND trial (2024), mania was one of two serious adverse events judged possibly related to TMS. The confidence interval above also means a moderately increased risk cannot be excluded. And nearly all of this evidence comes from people who were taking mood-stabilizing medication throughout.

Mood stabilizer cover

The trials did not test TMS alone in bipolar disorder. In the deep TMS trial, stimulation was an add-on for patients receiving adequate pharmacotherapy; the iTBS trial required current treatment with a mood stabilizer, an atypical antipsychotic or both; and the accelerated trial required a mood stabilizer for at least four weeks beforehand. The safety figures above therefore describe TMS added to protective medication. They say little about TMS in someone with bipolar disorder who is taking no mood stabilizer.

Guidelines place TMS accordingly. The CANMAT and ISBD guidelines list adjunctive rTMS as a third-line option for acute bipolar I depression, to be considered after first- and second-line medications, with ECT at second line, particularly for treatment-refractory illness or when a rapid response is needed. A 2018 US consensus statement on TMS likewise advises that patients with psychotic symptoms or acute suicidal ideation be considered for treatments with established efficacy such as ECT. TMS vs ECT compares the two, and combining TMS with medication covers what is known about TMS alongside drug treatment more generally.

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.

Regulatory and insurance status

A 2026 review states that TMS recently received FDA breakthrough status for bipolar depression; the designation could not be confirmed from an FDA source for this article. Breakthrough status is a designation intended to speed development and review; it is not a clearance, and it does not change what the devices are labeled for today.

Insurance follows the labels. Aetna lists bipolar and other mood disorders apart from major depression among the conditions for which it considers TMS experimental, and Optum lists bipolar disorder among unproven indications. The Carelon request form asks the clinician to attest that there is no history of manic, mixed or hypomanic episodes. New York Medicare's coverage criteria are written for adults with confirmed major depressive disorder. In practice this means TMS for bipolar depression is usually self-pay. The plan-specific pages, such as Aetna's TMS criteria and UnitedHealthcare and Optum coverage, give the policy language.

Who might consider it, and who should not

Given off-label status, mixed efficacy data and the cost, TMS is not an early step in bipolar depression. It becomes a reasonable discussion when all of the following apply:

• The diagnosis is clear and the current episode is depressive, without mixed features.
• Guideline-recommended medications for bipolar depression have been tried at adequate doses without enough benefit, or were not tolerated.
• A mood stabilizer or atypical antipsychotic is in place and will continue through the course.
• The patient understands that the use is off-label and that the evidence is weaker than for unipolar depression.
• A psychiatrist will monitor mood, sleep and energy closely during treatment, and there is a plan for what happens if hypomanic symptoms appear.

The published trials do not support TMS for people in a manic, hypomanic or mixed state, those with psychotic symptoms, or those in an acute suicidal crisis. The trials enrolled people in a depressive episode, so how the switch data apply to someone with rapid cycling or a very recent manic episode is not known. The standard TMS safety screening for seizure risk and metal implants applies as it does for anyone; see TMS safety and seizure risk.

What to watch for during a course

The early signs of a switch are the familiar ones: sleeping much less without feeling tired, unusual energy or irritability, racing thoughts, faster speech, and uncharacteristic spending or risk-taking. The deep TMS trial tracked them with the Young Mania Rating Scale, a standard clinician questionnaire. Anyone having TMS with a bipolar diagnosis, and the people close to them, should know these signs and report them promptly, because the usual response is to pause treatment and reassess. The site's article on early warning signs of a bipolar episode describes them in detail, and its bipolar disorder treatment page covers the practice's general approach to the condition.

The rest of this series is collected in the TMS guide, and the practice's current TMS information is on the TMS service page.

Frequently asked questions

Is TMS FDA-cleared for bipolar depression?

No. TMS devices are cleared for major depressive disorder and a few other conditions, not bipolar depression. Use in bipolar depression is off-label.

Can TMS trigger mania?

It can, but in pooled trial data the rate has been low and similar to sham treatment. Almost all of those patients were taking a mood stabilizer or antipsychotic, so the figures apply to TMS added to that protection.

Do I need to be on a mood stabilizer to have TMS with bipolar disorder?

The main trials required one, and guidelines place TMS as an add-on to medication in bipolar depression. Having TMS without mood-stabilizing medication is not what the evidence describes.

Will insurance pay for TMS for bipolar depression?

Usually not. Major insurers such as Aetna and Optum classify TMS for bipolar disorder as experimental or unproven, so it is typically self-pay.

Is TMS safer than antidepressants in bipolar disorder?

That comparison has not been tested directly. Guidelines advise against antidepressants alone in bipolar I depression, and TMS switch rates in trials have been low, but the two have not been compared head to head.

Does bipolar II respond differently from bipolar I?

The trials enrolled both types and were too small to say. In the 2026 meta-analysis, a little over half of participants in trials reporting subtype had bipolar II disorder.

Sources

1. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disorders, 2018. pmc.ncbi.nlm.nih.gov
2. Transcranial Magnetic Stimulation for Bipolar Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Canadian Journal of Psychiatry, 2026. pubmed.ncbi.nlm.nih.gov
3. Efficacy, Effectiveness, and Safety of Transcranial Magnetic Stimulation for Bipolar Depression: A Systematic Review and Meta-Analysis. Biological Psychiatry Global Open Science, 2026. pubmed.ncbi.nlm.nih.gov
4. Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial. Neuropsychopharmacology, 2017. pubmed.ncbi.nlm.nih.gov
5. Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial. JAMA Network Open, 2021. pubmed.ncbi.nlm.nih.gov
6. Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry, 2024. pubmed.ncbi.nlm.nih.gov
7. The efficacy and safety of theta burst stimulation for bipolar depression: a systematic review and meta-analysis. Journal of Psychiatric Research, 2025. pubmed.ncbi.nlm.nih.gov
8. FDA 510(k) K160703 (NeuroStar TMS Therapy System). U.S. FDA, 2016. accessdata.fda.gov
9. 510(k) K122288: BrainsWay Deep TMS System. U.S. FDA, 2013. accessdata.fda.gov
10. openFDA 510(k) records, applicant Magnus. U.S. FDA (openFDA), 2026. api.fda.gov
11. Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial. Nature Medicine, 2024. pubmed.ncbi.nlm.nih.gov
12. Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. International Journal of Neuropsychopharmacology, 2008. europepmc.org
13. Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders: A systematic review and meta-analysis. World Journal of Psychiatry, 2021. europepmc.org
14. Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems. U.S. FDA, 2011. fda.gov
15. 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
16. Transcranial Magnetic Stimulation LCD L33398 (v40). CMS, 2026. cms.gov
17. Transcranial Magnetic Stimulation and Cranial Electrical Stimulation (Clinical Policy Bulletin 0469). Aetna, 2026. aetna.com
18. Behavioral Clinical Policy: Transcranial Magnetic Stimulation. Optum Behavioral Health Solutions, 2026. providerexpress.com
19. Carelon Behavioral Health Repetitive Transcranial Magnetic Stimulation Request Form (commercial contracts). Carelon Behavioral Health, undated. carelonbehavioralhealth.com

Educational information, not medical advice. Whether TMS or any treatment fits you is a decision to make with a psychiatrist who knows your history.