Optimizing the Use of More Efficacious Treatments in Treatment Resistant Depression

In this episode, Dr Anita Clayton and experts discuss positioning of efficacious treatments in TRD.

Using a vivid analogy, Dr. Trinh framed urgent, effective treatment as bringing a hose rather than buckets to a house fire — emphasizing that faster, more effective interventions should be prioritized over cautious, stepwise approaches when clinically appropriate. Panelists agreed that waiting too long through inadequate treatment trials causes unnecessary suffering and may entrench depression neurologically, making recovery progressively harder.

A structured response framework was outlined: non-response (0–24% improvement) should prompt dose escalation or treatment change within weeks; inadequate response (25–49%) may warrant adjunctive therapy; and true response requires at least 50% improvement from baseline. Panelists challenged the assumption that SSRIs must always be the starting point, noting that numerous effective generic antidepressants with different mechanisms exist and can better accommodate individual patient preferences around weight, sleep, and sexual function.

Measurement-based care was strongly endorsed as essential to timely decision-making. Dr. Citrome shared a striking anecdote of a patient who scored 22 on the PHQ-9 despite appearing well outwardly — illustrating how depression, particularly in women socialized to conceal distress, can be profoundly underestimated without objective measurement tools. Routine use of standardized scales was presented as a non-negotiable component of quality depression care.

In the next episode, “Side Effect Profiles and Discontinuation Rates of NMDA Receptor Antagonists in Treatment Resistant Depression,” panelists discuss the safety and tolerability profiles of esketamine and dextromethorphan-bupropion, highlighting their low discontinuation rates and transient side effects as meaningful advantages over traditional antidepressants and adjunctive antipsychotics.