Both inflammation and smoking can influence a drug’s pharmacokinetic properties, i.e., its liberation, absorption, distribution, metabolism, and elimination. Depending on, e.g., pharmacogenetics, these changes may alter treatment response or cause serious adverse drug reactions and are thus of clinical relevance. Antipsychotic drugs, used in the treatment of psychosis and schizophrenia, should be closely monitored due to multiple factors (e.g., the narrow therapeutic window of certain psychotropic drugs, the chronicity of most mental illnesses, and the common occurrence of polypharmacotherapy in psychiatry). Therapeutic drug monitoring (TDM) aids with drug titration by enabling the quantification of patients’ drug levels. Recommendations on the use of TDM during treatment with psychotropic drugs are presented in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; however, data on antipsychotic drug levels during inflammation or after changes in smoking behavior—both clinically relevant in psychiatry—that can aid clinical decision making are sparse. The following narrative review provides an overview of relevant literature regarding TDM in psychiatry, particularly in the context of second- and third-generation antipsychotic drugs, inflammation, and smoking behavior. It aims to spread awareness regarding TDM (most pronouncedly of clozapine and olanzapine) as a tool to optimize drug safety and provide patient-tailored treatment.

Background: Major depressive disorder (MDD) represents a tremendous health threat to the world’s population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in ECT’s mode of action. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are involved in BDNF production. Hypothesis: The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. Methods: We withdrew blood from two cohorts of treatment-resistant MDD patients receiving ECT. In the first cohort (n = 59), blood was collected at baseline only. To evaluate DNA methylation changes throughout the treatment course, we acquired a second group (n = 28) and took blood samples at multiple time points. DNA isolated from whole blood and defined immune cell subtypes (B cells, monocytes, natural killer cells, and T cells) served for epigenetic analyses. Results: Mixed linear models (corrected for multiple testing by Sidak’s post-hoc test) revealed (1) no detectable baseline blood DNA methylation differences between ECT remitters (n = 33) and non-remitters (n = 53) in the regions analyzed, but (2) a significant difference in t-PA’s DNA methylation between the investigated immune cell subtypes instead (p < 0.00001). This difference remained stable throughout the treatment course, showed no acute changes after ECT, and was independent of clinical remission. Conclusion: DNA methylation of both proteins seems to play a minor role in ECT’s mechanisms. Generally, we recommend using defined immune cell subtypes (instead of whole blood only) for DNA methylation analyses.

Introduction Precision medicine in psychiatry is still in its infancy. To establish patient-tailored treatment, adequate indicators predicting treatment response are required. Electroconvulsive therapy (ECT) is considered one of the most effective options for pharmacoresistant major depressive disorder (MDD), yet remission rates were reported to be below 50%. Methods Since epigenetics of the stress response system seem to play a role in MDD, we analyzed the DNA methylation (DNAm) of genes encoding the glucocorticoid receptor (NR3C1) and proopiomelanocortin (POMC) through Sanger Sequencing. For analysis, blood was taken before and after the first and last ECT from MDD patients (n=31), unmedicated depressed controls (UDC; n=19, baseline), and healthy controls (HC; n=20, baseline). Results Baseline DNAm in NR3C1 was significantly lower in UDCs compared to both other groups (UDC: 0.014(±0.002), ECT: 0.031(±0.001), HC: 0.024(±0.002); p<0.001), whereas regarding POMC, ECT patients had the highest DNAm levels (ECT: 0.252(±0.013), UDC: 0.156(±0.015), HC: 0.162(±0.014); p<0.001). NR3C1m and POMCm decreased after the first ECT (NR3C1: p<0.001; POMC: p=0.001), and responders were less methylated compared to non-responders in NR3C1(p<0.001). Discussion Our findings indicate that both genes might play a role in the chronification of depression and NR3C1 may be relevant for ECT response prediction. ^* These authors share the first authorship Received: 13 June 2022 Received: 27 December 2022 Accepted: 06 February 2023 Article published online: 21 March 2023 © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/). Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background.Electroconvulsive therapy (ECT) is one of the most effective treatment options for refractory depressed patients. To date, there are only a few predictors of response.Aim.The aim was to identify predictive biomarkers of remission to ECT on a molecular level.Methods. 11 patients suffering from a major depressive episode—according to the Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)—underwent 10 ECT sessions. Blood samples were taken, and the depression severity was assessed before, one hour and 24 hours after sessions 1, 4, 7, and 10 using the Montgomery Asberg Depression Rating Scale (MADRS). A MADRS total score < 12 was interpreted as remission.Results.Patients remitting under ECT had significantly higher homocysteine (p<0.001), S100B (p<0.001), and procalcitonin (PCT) (p=0.027) serum levels. On the contrary, serum levels of vitamin B12 (p<0.001) and folic acid (p=0.007) were significantly lower in remitters compared to those in nonremitters. Levels remained unchanged throughout the whole ECT course.Conclusions.Our findings indicate that lower levels of vitamin B12 and folic acid associated with higher levels of homocysteine, S100B, and PCT point to a subgroup of depressed patients sensitive to ECT. Due to the limited sample size, further studies are required to replicate our findings.