How is treatment-resistant depression defined?

Failure to respond to two or more antidepressants at adequate dose and duration. Approximately 30–40% of people with depression are treatment-resistant.

What options exist beyond antidepressants?

Augmentation (adding atypical antipsychotics), ketamine infusions, TMS, ECT, psychotherapy intensification, lifestyle modifications, and medication switching.

What is transcranial magnetic stimulation (TMS)?

TMS uses magnetic pulses to stimulate brain regions involved in depression. It's FDA-approved with good evidence for treatment-resistant depression.

Yes. Electroconvulsive therapy remains highly effective for severe, treatment-resistant depression, especially with suicidal ideation. Modern ECT is safer with anesthesia.

Sciencedepression-screener

Treatment-Resistant Depression: When Medications Don't Work

Peter Kolomiets

|March 30, 2026|Updated Apr 13, 2026|7 min

Treatment-Resistant Depression: When Medications Don't Work

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References

Fava M (2003). Treatment-Resistant Depression: Epidemiology, Mechanisms, and Management
George MS, Lisanby SH, Avery D (2006). Transcranial Magnetic Stimulation for Depression