Toward Precision Psychiatry: Innovations and Prospects in Treating Depression.

Importance: Major depressive disorder is a heterogeneous disorder affecting over 280 million people globally. Despite multiple treatment options, individual response to drugs varies significantly, and most patients go through a trial-and-error approach, resulting in multiple drug iterations before alleviation of symptoms is achieved. Treatment optimization is further complicated by lack of full elucidation of the neurobiology of depression. The high prevalence of nonresponse, coupled with the detrimental effects of prolonged disease on patient welfare, economic burden, and increased likelihood of recurrence, substantiates the critical need for robust tools capable of precisely matching patients with their most effective and safe treatment options in a time-sensitive manner. Observations: Research into technologies that tailor treatments to individual patients based on their unique molecular and cellular characteristics has led to the development of precision medicine tools ranging from pharmacogenetics through peripheral biomarkers and neuroimaging to a platform that uses patient-derived neurons as a substrate for in vitro patient-specific functional readouts. Conclusions and relevance: Novel precision medicine tools in depression are being introduced that aim to identify the optimal treatment for each patient. Such tools have the potential to significantly improve depression management by guiding treatment selection for prescribers and people with lived experience. Prim Care Companion CNS Disord 2025;27(5):25nr03970. Author affiliations are listed at the end of this article.