In this episode of PsyQ, we take a critical look at the evolution of major depression treatment over the past two decades. We start with the foundational Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, a study that has shaped clinical practice for years with its widely cited ~70% cumulative remission rate. However, we then dive deep into a startling 2023 re-analysis that challenges this cornerstone of psychopharmacology, revealing a cumulative remission rate closer to 35% when the original study's protocol is strictly followed. This critical re-evaluation serves as a springboard to explore the future, as we discuss a 2024 review on the novel and emerging treatments moving beyond monoamines, including glutamatergic agents like ketamine and the promising field of psychedelic-assisted therapy. Join us as we journey from the bedrock of modern depression treatment to the cutting edge of psychiatric research.

Articles Discussed:

Rush AJ, Fava M, Wisniewski SR, et al. Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Control Clin Trials. 2004.

Pigott HE, Kim T, Xu C, et al. What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study’s patient-level data with fidelity to the original research protocol. BMJ Open. 2023.

Ghasemi M, Rezaei F, Falahati F, et al. Trends in research on novel antidepressant treatments. Frontiers in Pharmacology. 2024.

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