Treatment-resistant depression

Treatment-resistant depression is depression that has not improved adequately after one or more appropriate treatments. Definitions vary in how many treatments must fail and what counts as an adequate response.

Antidepressant: A medication used to treat depressive and other mental disorders by altering neurotransmission or related biological processes. Most definitions assess resistance after an adequate antidepressant trial.
Switching antidepressants: Replacing one antidepressant with another when the first is ineffective or poorly tolerated. A medication switch is a common next step after an inadequate trial.
Treatment-refractory depression: Depression that has failed to respond to multiple adequate treatments, often used interchangeably with treatment-resistant depression. The terms overlap, though refractory depression can imply a more severe degree of nonresponse.
Treatment-resistant depression criteria: Clinical thresholds used to decide whether depression has resisted treatment, including the number and adequacy of failed trials. Different thresholds produce different diagnoses and estimates of how common resistance is.
Antidepressant tachyphylaxis: The loss of a medication's therapeutic effect despite continued use at the same dose. Symptoms returning during ongoing medication can resemble treatment resistance.
Antidepressant augmentation: Adding a second treatment to an antidepressant to improve its therapeutic effect. Augmentation can help when an antidepressant has produced only a partial response.
Partial response (psychiatry): A clinically meaningful but incomplete improvement in symptoms after treatment. Partial improvement differs from no response and can guide augmentation rather than switching.
Biomarker (medicine): A measurable biological characteristic that indicates a normal process, disease process, or response to treatment. No validated biomarker reliably selects the next treatment for an individual case.
Pharmacokinetics: The study of how the body absorbs, distributes, metabolizes, and eliminates drugs. Drug interactions or rapid metabolism can reduce exposure and mimic an ineffective treatment.
Cognitive behavioral therapy: A structured psychotherapy that targets unhelpful patterns of thought and behavior. Psychotherapy may be added when medication alone has not brought adequate improvement.

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