Compared with that in previous decades, a prolonged phase of marked stagnation in the development of novel neuropsychopharmacological agents has recently been observed.1 Along with this lack of breakthroughs, there has been increasing awareness of the need to understand the effectiveness and tolerability patterns of well-established and widely prescribed psychotropic agents. In contrast to research regarding the identification of reliable treatment biomarkers, therapeutic drug monitoring (TDM) is neither novel nor impressively innovative. However, TDM remains among the few valuable routine clinical tools in neuropsychopharmacology that essentially account for interindividual variability. This special issue of Therapeutic Drug Monitoring focuses on the unfolding potential of TDM as part of the clinical routine for neuropsychotropic agents. Scherf-Clavel et al2 guide us through the frequently unseen parts of the TDM process, including various steps from requesting TDM to obtaining and integrating TDM results into clinical decision algorithms. A critical aspect of TDM utility in clinical routine is the turnaround time, that is, the time between requesting TDM and communicating TDM results. Vincent et al3 show how short turnaround times for clozapine have the potential to transform TDM into a first-line decision-making tool in sudden or unforeseen situations. These situations may be related to the abrupt drug bioavailability changes linked to immunologic reactions4 or bariatric operations5 and may ultimately lead to side effects.6,7

The studies included in this special issue highlight the value of TDM as part of the treatment of particularly vulnerable patient subgroups such as women in pregnancy and lactation, and children. Hagenkötter et al8 provide a systematic review of the therapeutic reference ranges for attention-deficit hyperactivity disorder medications in children and adolescents to optimize treatment outcomes. Another systematic review investigated clozapine concentration-to-dose ratios as an index of drug clearance in children and adolescents treated with clozapine for mental disorders.9 Apart from children and adolescents, TDM holds strong potential in the treatment of women during pregnancy and lactation. Goo et al10 systematically reviewed evidence on lamotrigine dose adjustments during pregnancy in light of pregnancy-related physiologic changes and the resulting pharmacokinetic alterations. A central challenge in the treatment of women during pregnancy and lactation is drug exposure of the newborn.11 Because TDM can help quantify drug exposure in newborns during lactation,11 Le Marois et al12 present a validated routine technique for the quantification of 14 psychotropic drugs in the plasma and breast milk. Alternative target matrices for TDM include hair and urine.13 Regarding sex effects, Spadi et al14 provide unique evidence supporting menstrual cycle phase-dependent patterns in the blood levels of several psychotropic agents. In addition to new technologies, novel metabolites of psychotropic agents are expected to gain attention, further enhancing the utility of TDM.15

Ultimately, TDM remains a simple yet valuable tool to assist in the continuous and strenuous efforts of clinicians to effectively deal with variability and all contributing factors, such as demographic and clinical characteristics,16 when used appropriately.17

1. Emsley R. The future of psychopharmacology: challenges beyond efficacy and tolerability. World Psychiatry. 2023;22:82–83. 2. Scherf-Clavel M, Baumann P, Hart XM, et al. Behind the curtain: therapeutic drug monitoring of psychotropic drugs from a laboratory analytical perspective. Ther Drug Monit. 2023. 3. Vincent P, Lesage A, Lalonde P, et al. A short turnaround of clozapine blood levels within 6 hours is essential for effective management of severely ill persons with treatment-resistant schizophrenia Ther Drug Monit. 2024. 4. Kuzin M, Gardin F, Gotschi M, et al. Changes in psychotropic drug blood levels after SARS-CoV-2 vaccination: a two-center cohort study. Ther Drug Monit. 2023. 5. Schoretsanitis G, Strommen M, Krabseth HM, et al. Effects of sleeve gastrectomy and Roux-en-Y gastric bypass on escitalopram pharmacokinetics: a cohort study. Ther Drug Monit. 2023. 6. Kuzin M, Haen E, Kuzo N, et al. Assessing pharmacokinetic correlates of escitalopram-related adverse drug reactions. Ther Drug Monit. 2024. 7. Heger K, Kjeldstadli K, Ring N, et al. Landmark CJ pharmacokinetic variability of sulthiame: the impact of age, drug-drug interactions and biochemical markers of toxicity in patients with epilepsy. Ther Drug Monit. 2023. 8. Hagenkötter SS, Rauh R, Clement HW, et al. Therapeutic reference ranges for ADHD medications in children and adolescents: a systematic review. Ther Drug Monit. 2024. 9. Jiménez-Fernández S, Gurpegui M, Correll CU, et al. A systematic review of clozapine concentration-to-dose ratios from therapeutic drug monitoring studies in children and adolescents treated with clozapine for mental disorders. Ther Drug Monit. 2024. 10. Goo Y, der Nederlanden AM, Bleasel A, et al. Dose monitoring of lamotrigine monotherapy in pregnancy: are pregnant women with epilepsy currently optimally managed? A systematic critical review. Ther Drug Monit. 2024. 11. Schoretsanitis G, Westin AA, Deligiannidis KM, et al. Excretion of antipsychotics into the amniotic fluid, umbilical cord blood, and breast milk: a systematic critical review and combined analysis. Ther Drug Monit. 2020;42:245–254. 12. Le Marois M, Doudka N, Tzavara E, et al. Simultaneous quantification of psychotropic drugs in human plasma and breast milk and its application in therapeutic drug monitoring and peripartum treatment optimization. Ther Drug Monit. 2023. 13. La Maida N, Di Giorgi A, Pichini S, et al. Comprehensive monitoring of psychoactive substances by LC-HRMS in psychiatric patients: a key tool for treatment planning and understanding consumption patterns in Rome, Italy. Ther Drug Monit. 2024. 14. Spadi J, Scherf-Clavel M, Leutritz AL, et al. Menstrual cycle associated changes in psychotropic drug levels: a pilot study. Ther Drug Monit. 2024. 15. Wollmann BW, Haugen AG, Smith RL, et al. Novel identification of cysteinyl derivates of toxic clozapine nitrenium ions and effect of valproic acid on metabolite formation: a study using reprocessed high-resolution mass spectra of analyzed TDM samples. Ther Drug Monit. 2024. 16. Berneri M, Jha U, O'Halloran S, et al. Validation of population pharmacokinetic models for clozapine dosage prediction. Ther Drug Monit. 2024. 17. Bhavsar NC, Dopheide JA, Botello TE, et al. Therapeutic drug level monitoring of antipsychotics at an inpatient psychiatric hospital. Ther Drug Monit. 2024.