Treatment-Resistant Depression

Treatment-resistant depression (TRD) is defined as failing to respond adequately to at least two antidepressants from different classes, used at an adequate dose and duration (usually 6–8 weeks at a therapeutic dose). It affects roughly 30% of people with MDD.

Approaches to TRD include: optimizing the dose of the current medication, switching to an antidepressant from another class, augmentation (adding another agent to the antidepressant — lithium, quetiapine, aripiprazole, buspirone), combining antidepressants, and non-pharmacological treatments such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and intranasal ketamine/esketamine (Spravato — recently approved for TRD).

It's also essential to investigate causes of "pseudo-resistance": incorrect diagnosis, untreated comorbidities (hypothyroidism, substance use, bipolar disorder), inconsistent medication adherence, or insufficient dosing.