The Thrive Journal · Psychiatry
What “treatment-resistant depression” actually means — and what comes next
By Dr. Jason Borrego, DNP, PMHNP-BC, CRNA
“Treatment-resistant” is one of the most discouraging phrases in psychiatry — and one of the most misunderstood. Clinically, it usually means depression that hasn’t responded adequately to two or more antidepressants, taken at a real dose for a real duration. It does not mean untreatable. It means the standard first steps weren’t your steps.
First: was it really a fair trial?
A surprising number of “failed” medications were never truly tried — dose too low, duration too short, side effects unmanaged, or the wrong diagnosis underneath (thyroid disease, sleep apnea, ADHD, perimenopause, and bipolar spectrum conditions all masquerade as resistant depression). A careful re-evaluation, sometimes with lab work and pharmacogenomic context, is step one — not another random medication.
Then: the escalation ladder
When depression is genuinely treatment-resistant, there is a real ladder, with evidence at each rung: optimizing or augmenting medication; structured therapy; Spravato® (esketamine), FDA-approved for exactly this situation and often insurance-covered; IV ketamine, studied head-to-head against ECT in the ELEKT-D trial with a 55.4% response rate over three weeks; and TMS. The point isn’t any single treatment — it’s that a plan exists past the point where most care stops.
What to ask any clinic (including ours)
How will you measure whether I’m improving? What happens if this doesn’t work — what’s the next rung? Who monitors me during advanced treatments, and what’s their training? If a practice can’t answer those three plainly, keep looking. Depression that resists treatment deserves a team that doesn’t shrug — it escalates, measures, and tells you the truth at every step.
See how we structure this at our psychiatry page and the advanced pathways page.
Wondering what the right next step is for you?