Advancing precision psychiatry and targeted treatments: Insights from immunopsychiatry

Abstract

Despite tremendous advancements in neuroscience, there has been limited impact on patient care. Current psychiatric treatments are largely non-specific, and drug development is hindered by outdated, overinclusive diagnostic categories and a "one-size-fits-all" approach. Additionally, mechanisms underlying psychiatric illnesses and their treatments with conventional medications remain poorly understood. Precision psychiatry is a strategy that holds great promise for novel therapies targeting specific pathophysiologic mechanisms in selected patients, ultimately contributing to more effective, personalized treatments. Immunopsychiatry, which focuses on the immune system's role in psychiatric disorders, exemplifies the challenges and potential solutions for precision psychiatry. Despite understanding how inflammation contributes to psychiatric illness, results of clinical trials with anti-inflammatory drugs have been inconsistent and underwhelming. Shortcomings of these trials include a lack of focus on subgroups of patients with increased inflammation, the use of non-specific outcome variables (e.g., not specific to inflammation's impact on the brain and behavior), and failure to establish target engagement of the inflammatory response. To advance anti-inflammatory treatments, clinical trials should: 1) enrich for patients using predictive biomarkers; 2) use clinical outcome assessments that align with inflammation's effects on the brain; 3) consider novel diagnostic constructs linked to inflammation; and 4) verify target engagement. Moreover, greater attention should be paid to efforts to repurpose available anti-inflammatory drugs while awaiting development of novel treatments targeting more specific immune pathways. Taken together, a collaborative approach involving academia, industry, funding agencies, patients, payors, and policymakers is required to advance Immunopsychiatry and ultimately provide a roadmap for successful implementation of precision psychiatry.

Keywords: Anti-inflammatory drugs; Biomarkers; Clinical Outcome Assessments; Clinical Trials; Depression; Drug development; Immunopsychiatry; Inflammation; Personalized Medicine; Psychiatry.