Factors Guiding Treatment Selection in Treatment Resistant Depression

In this episode, Dr Anita Clayton and experts discuss factors that inform treatment choices in TRD.

Panelists emphasized that TRD treatment selection should begin with patient preference and practical considerations — such as ability to attend frequent office visits, transportation requirements, and contraindications like non-removable metal implants for neuromodulation. Given the heterogeneity of TRD, no single treatment is universally superior, though certain clinical scenarios may favor specific approaches. Esketamine was highlighted as particularly appropriate for patients with acute suicidal ideation — a unique on-label indication — and in cases involving trauma or neuroinflammation.

Glutamatergic agents were strongly advocated for earlier use, with panelists noting that dextromethorphan-bupropion demonstrated statistically significant and clinically meaningful improvement as early as day 7 — a speed unmatched by traditional oral antidepressants. Esketamine similarly produces rapid functional improvements, with patients often reporting feeling noticeably better within days. This rapid response was noted to meaningfully strengthen the therapeutic alliance, making patients more receptive to further treatment recommendations.

Panelists also underscored glutamate's fundamental importance — comprising approximately 40% of brain neurotransmitters compared to less than 1% each for serotonin, dopamine, and norepinephrine. Dr. Citrome reinforced that the PHQ-9's often-overlooked tenth question — addressing functional impact — is essential for capturing what truly matters to patients beyond symptom scores alone.

Check out https://link.springer.com/article/10.1007/s40263-024-01114-y for more information on glutamatergic modulators of depression.

In the next episode, “Esketamine for Treatment Resistant Depression,” panelists discuss results of SUSTAIN3 and the critical importance of long-term monitoring and maintenance therapy after achieving remission in TRD, emphasizing that ongoing medical evaluation, psychotherapy, and proactive surveillance are essential to sustaining recovery and preventing relapse.