What is treatment-resistant depression?

Depression that has not responded adequately to at least two different antidepressant medications taken at adequate doses for adequate duration. Approximately 30% of people with major depression experience treatment resistance.

Does TMS work for depression?

Yes. TMS produces response rates of 50-60% for treatment-resistant depression. The newer SAINT protocol achieves approximately 79% remission rates in just 5 days of treatment.

Is ketamine approved for depression?

Esketamine (Spravato), a nasal spray form, is FDA-approved for treatment-resistant depression. IV ketamine is used off-label. Both are administered in supervised clinical settings.

Condition-specific

Treatment options for treatment-resistant depression (TRD)

Published June 8, 2025 · 10 min read · Last updated April 2026

Reviewed for accuracy — Written and reviewed by licensed clinical professionals. Editorial process.

Roughly 30% of people with major depressive disorder don't respond adequately to two or more standard antidepressant trials. This is clinically defined as treatment-resistant depression (TRD), and it requires a different approach than continuing to cycle through SSRIs and SNRIs.

Transcranial Magnetic Stimulation (TMS)

TMS uses magnetic pulses to stimulate specific brain regions involved in mood regulation. It's FDA-cleared for treatment-resistant depression, non-invasive, performed in an outpatient setting, and typically involves 30-36 sessions over 6-9 weeks. Response rates for TRD patients are approximately 50-60%, with about one-third achieving full remission. Newer protocols like accelerated TMS (Stanford SAINT protocol) can deliver a full course in 5 days.

Ketamine and esketamine (Spravato)

Esketamine (Spravato) is an FDA-approved nasal spray for TRD, administered in a certified healthcare setting. IV ketamine infusions, while not FDA-approved specifically for depression, are offered at ketamine clinics nationwide. Both can produce rapid antidepressant effects — often within hours or days rather than weeks. They represent a different mechanism than traditional antidepressants, targeting the glutamate system rather than serotonin.

Electroconvulsive Therapy (ECT)

ECT remains the most effective treatment for severe, treatment-resistant depression, with response rates of 70-90%. Modern ECT is performed under general anesthesia, uses brief-pulse stimulation, and is far more refined than historical depictions. It's typically considered when other treatments have failed and the depression is severe or life-threatening.

Finding specialized care

Not every treatment facility offers TMS, ketamine, or ECT. When searching for TRD treatment, ask specifically which advanced modalities the facility offers and whether their psychiatrists have experience with treatment-resistant cases.