What is it about?
When depression does not improve after standard treatments, doctors often call it "treatment-resistant." This article argues that the label itself is part of the problem. A single review once counted 155 different definitions of treatment-resistant depression, and major regulators in Europe and the United States use different criteria — so the same patient can be considered "resistant" in one clinic and not in another. The article shows how this confusion has real costs: patients may be labelled resistant too soon, when the real issue is an inadequate dose, poor adherence, individual differences in how the body processes medication, or an overlooked diagnosis — a situation known as "pseudoresistance." The current framework also focuses too narrowly on medication, sidelining psychotherapy, life circumstances, trauma, and everyday functioning. As an alternative, the article makes the case for a broader model — "difficult-to-treat depression" — that treats persistent depression as something to be managed across biological, psychological, and social dimensions, bringing in psychotherapy, family involvement, and coordinated care earlier rather than after a long chain of failed drug trials.
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Why is it important?
Millions of people live with depression that does not respond to first treatments, and how we define their condition directly shapes the care they receive. This article matters because it targets a problem that is usually taken for granted: the very concept of "treatment resistance." When definitions vary this widely, studies cannot be compared, meta-analyses become unreliable, access to advanced therapies becomes a lottery, and patients are exposed to repeated, sometimes harmful, cycles of medication before other options are even considered. By exposing these definitional, clinical, and economic consequences together, the article makes the case that reform is not merely academic but a clinical and ethical priority. Its aim is to push clinicians, researchers, and regulators toward clearer, shared criteria and toward a model of care centred on how patients actually function and live — not only on how many drugs have failed.
Perspectives
After years of treating people whose depression would not lift, I have become convinced that we too often blame the patient's biology for the limits of our own frameworks. Calling someone "treatment-resistant" can quietly close doors: it suggests we have done all we can, when in reality the dose may have been too low, the diagnosis incomplete, or the person's life circumstances never addressed. I wrote this article because I believe the word "resistant" has come to describe the failure of a pharmacology-centred model more than the reality of the illness. Moving to a "difficult-to-treat" perspective is not a change of vocabulary but a change of stance — one that keeps the patient's functioning, relationships, and dignity at the centre. This is an argument, not a final answer, and I offer it in the hope of provoking the debate and the rigorous work that a fairer, more coherent definition still demands.
PhD in Neuroscience Walter Paganin
StudioPsicologiaSignorini
Read the Original
This page is a summary of: Treatment-resistant depression: time to rethink current definitions and clinical practice, Frontiers in Psychiatry, January 2026, Frontiers,
DOI: 10.3389/fpsyt.2025.1733678.
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