TRD
What Is Treatment-Resistant Depression?
Medically reviewed · Updated 2026
"Treatment-resistant depression" sounds like a dead end. It's actually the opposite — it's a specific clinical category with its own dedicated, effective treatments. Getting the label can be the thing that finally opens the right doors.
The definition
Treatment-resistant depression (TRD) is generally defined as depression that hasn't responded adequately to at least two different antidepressants, each taken at an adequate dose for an adequate duration. The precise threshold varies between guidelines, but the two-adequate-trials standard is the common working definition.
It's more common than people assume
A substantial share of people with depression — by many estimates around a third — don't achieve remission with their first or second medication. If that's you, you are not an outlier and you are not out of options. You've simply reached the point where the treatments designed specifically for this take over.
What's built specifically for TRD
- TMS (transcranial magnetic stimulation) — FDA-cleared for depression that hasn't responded to medication; non-invasive, no sedation, often insurance-covered after medication failures.
- Ketamine and esketamine (Spravato) — rapid-acting, working through a different mechanism than standard antidepressants; esketamine is FDA-approved specifically for TRD.
- ECT (electroconvulsive therapy) — the most effective treatment for severe or treatment-resistant depression, with response rates higher than most alternatives.
- Augmentation strategies — adding lithium, an atypical antipsychotic, or another agent to an existing antidepressant.
Mapping your options
Treatment Finder includes every option above and explains, in plain language, what each involves and what the evidence shows. Its short questionnaire factors in how long you've been dealing with symptoms and how severe they are — the exact inputs that separate a first-line plan from a TRD plan — then hands you a summary to review with your psychiatrist.
Put this into practice
Treatment Finder maps all 38 options to your situation and exports a PDF for your appointment. $4.99 once, no subscription. Get it on the App Store →
Educational reference, not medical advice. This does not diagnose or treat any condition and is not a substitute for a licensed clinician. In crisis, call or text 988 (US Suicide & Crisis Lifeline).