Microsampling for antidepressant drug analysis: Current state and perspectives

Microsampling has emerged as a highly promising approach for the quantitative analysis of antidepressant drugs, offering key benefits in terms of minimal invasiveness, reduced blood volume requirements, and suitability for decentralised and patient-centric sample collection. Historically, the clinical adoption of therapeutic drug monitoring (TDM) for antidepressants has lagged behind that for other CNS drugs, largely due to perceptions of a wide therapeutic window and moderate toxicity risk. However, growing recognition of pharmacokinetic variability, challenges in polypharmacy, and evolving models of personalised medicine, now highlight the critical need for robust and adaptable analytical strategies in this field. Technologies such as dried blood spot (DBS), volumetric absorptive microsampling (VAMS), capillary- and microfluidic-generated DBS, capillary microsampling (CMS) and novel hybrid/automated platforms have been developed and validated for antidepressant quantification across diverse settings—including clinical, preclinical and forensic applications. This review provides a comprehensive analysis of the principles, methodologies and translational relevance of microsampling for antidepressants, critically summarising evidence from original research papers and key review papers. We explore technical and analytical challenges including matrix effects, hematocrit variability, sample stability and the processes underpinning quantitative bridging to conventional matrices such as plasma and serum. Major recent advances, like operator-independent volumetric devices and workflow automation, are contextualised within the broader push toward remote and home-based monitoring. Clinical validation studies, animal model research and post-mortem investigations are reviewed to illustrate the wide range and adaptability of these technologies. By highlighting both achievements and unresolved barriers, this work demonstrates how microsampling is poised to transform antidepressant TDM, research and future psychiatric pharmacotherapy. • Overview of modern microsampling technologies for antidepressant analysis. • Method summary across experimental, clinical and forensic studies. • Emphasis on method bridging, patient-centric workflows and automation. • Methodological pitfalls and future trajectories for practical implementation.