Treatment Resistant Depression, Residual Symptoms, and Remission

Welcome back to another Psychiatric Times Peer Exchange series." In this episode titled "Treatment Resistant Depression, Residual Symptoms, and Remission," moderator Anita H. Clayton, MD discusses treatment resistant depression with Brittany Albright, MD, MPH, DABOM, William Sauvé, MD, Leslie Citrome, MD, MPH, Linda Trinh, DNP, PMHNP, FNP, MPH.

Treatment-resistant depression (TRD) lacks a formal APA or DSM definition, but is clinically understood as the failure of at least two adequate antidepressant trials — meaning appropriate dose and duration of at least 6–8 weeks. Originally coined by the WHO as a research definition, TRD is remarkably common in psychiatric practice; panelists noted that the majority of their patients with MDD meet this threshold. Importantly, one panelist reframed TRD as "monoamine treatment-resistant depression," emphasizing that medications are failing patients — not the other way around.

A critical nuance is ensuring prior treatment trials were truly adequate, as many patients report having "tried everything" but discontinued medications within days due to side effects or intolerance. This distinction matters before concluding a patient has true TRD.

Regarding residual symptoms, panelists agreed they are common even when partial response is achieved, and that full remission should always be the goal. Residual symptoms — such as sedation or persistent low mood — significantly increase relapse risk and impair daily functioning. Perspectives on remission can also differ between patient and provider. A comprehensive approach combining pharmacotherapy, psychotherapy, and attention to existential and situational factors was emphasized as essential to achieving and sustaining optimal outcomes.

In the next episode, “Revealing of Treatment Resistant Depression,” panelist discuss how TRD is revealed — not caused — by treatment, reflecting the complex, multifactorial neurobiology of depression and the limitations of repeatedly using the same classes of medications.