Background/Objectives: Therapeutic drug monitoring (TDM) of antipsychotic medications plays an important role in optimizing treatment efficacy, reducing adverse effects, and supporting adherence. While Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC–MS/MS) has long been the gold standard for antipsychotic quantification, recent advances in automated platforms and microsampling raise questions about its current clinical practicality. This systematic review evaluated the clinical applicability and analytical performance of UHPLC-based methods for monitoring antipsychotic drugs, focusing on precision, recovery, matrix effects, and suitability across various biological matrices. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted for studies published between 2013 and 2024 involving UHPLC-based quantification of antipsychotics in clinical samples from adult patients. Data on analytical parameters, sample matrices, and study characteristics were extracted. A custom quality checklist was used to assess methodological rigor. In addition to qualitative synthesis, non-traditional quantitative approaches were applied, including descriptive aggregation of recovery, matrix effects, and precision across studies, as well as correlation analyses to explore relationships among performance parameters. Results: Twelve studies were included, spanning a range of typical and atypical antipsychotics and metabolites. Plasma and serum demonstrated the highest analytical reliability (recovery >90%, minimal matrix effects), while dried blood spots (DBSs), whole blood, and oral fluid showed greater variability. Clinically, UHPLC–MS/MS enabled more accurate dose adjustments and identification of non-adherence, outperforming immunoassays in sensitivity, specificity, and metabolite detection. Microsampling methods showed promise for outpatient and decentralized care but require further clinical validation. Conclusions: UHPLC–MS/MS remains the most robust and reliable method for TDM of antipsychotics, especially when quantification of active metabolites is required. While logistical barriers remain, technological advances may enhance feasibility and support broader integration into routine psychiatric care.

Background/Objectives: Electroconvulsive therapy (ECT) remains the most effective biological treatment for treatment-resistant depression. Although its efficacy has been consistently demonstrated, the influence of seizure characteristics and treatment parameters on clinical outcomes in routine practice remains incompletely understood. This study aimed to evaluate the effectiveness of seizure threshold-titrated ECT in patients with treatment-resistant depression and to describe treatment outcomes in relation to seizure expression and technical treatment variables. Methods: We conducted a retrospective naturalistic study at the Department of ECT, Dr. Gh. Preda Clinical Psychiatric Hospital, Sibiu, Romania. Consecutive patients treated with ECT for treatment-resistant depressive episodes between March 2022 and December 2025 were included. Clinical outcomes were assessed before and after treatment using the Montgomery–Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Mini-Mental State Examination (MMSE), and Global Assessment of Functioning Scale (GAF). Information regarding electrode placement, seizure threshold, seizure duration, the number of ECT sessions, and concomitant psychotropic medication was collected from medical records. Results: Nineteen acute ECT courses were available for outcome analysis. Depressive symptom severity improved significantly following treatment, with median MADRS scores decreasing from 38 (IQR 36–41) to 20 (IQR 9.5–24) (p < 0.001). A clinical response was observed in 57.9% of courses, while 36.8% achieved remission. Similar improvements were noted in self-reported depressive symptoms and overall functioning, with median BDI scores decreasing from 38 to 16 and median GAF scores increasing from 55 to 65. MMSE scores remained stable throughout treatment. Considerable variability was observed in both motor and EEG seizure durations; however, no consistent relationship between seizure duration and antidepressant response was identified. Discussion: The observed outcomes are consistent with previous evidence supporting ECT as an effective intervention for severe depressive illness. Functional improvement accompanied symptom reduction, while no decline in global cognitive performance, as assessed by the MMSE, was observed. In this cohort, seizure duration alone did not appear to provide meaningful information regarding treatment response. Conclusions: Seizure threshold-titrated ECT was associated with substantial clinical improvement in patients with treatment-resistant depressive episodes, accompanied by improved functioning and stable global cognitive performance. These findings support the continued use of individualized ECT protocols in routine clinical practice and highlight the need for further research on neurophysiological predictors of treatment outcome.