Pharmacopsychiatry最新文献

{"title":"Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2026 - Pharmacokinetic, pharmacogenetic and clinical aspects.","authors":"Xenia M Hart, Gerhard Gründer, Christoph Hiemke, Ivana Adamovic, Friederike Amann, Pierre Baumann, Niels Bergemann, Christian Brandt, Hans-Willi Clement, Andreas Conca, Jürgen Deckert, Otto Dietmaier, Gabriel Eckermann, Karin Egberts, Katharina Endres, Nicole Erlacher, Stefanie Fekete, Stefano Ferrea, Vincenzo Florio, Manfred Gerlach, Ekkehard Haen, Martina Hahn, Ursula Havemann-Reinecke, Gudrun Hefner, Wolfgang H Jost, Maxim Kuzin, Gerd Laux, Stefan Leucht, Ignazio Maniscalco, Andreas Menke, Thomas Messer, Rainald Moessner, Daniel J Müller, Thomas Müller, Michael Paulzen, Holger Petri, Philippe Pfeifer, Bruno Pfuhlmann, Peter Riederer, Sibylle C Roll, Maike Scherf-Clavel, Markus Schwarz, Werner Steimer, Julia C Stingl, Sermin Toto, Sven Ulrich, Gerald Zernig, Gabriela Zurek, Stefan Unterecker, Georgios Schoretsanitis","doi":"10.1055/a-2860-7861","DOIUrl":"10.1055/a-2860-7861","url":null,"abstract":"<p><strong>Abstract: </strong>TDM involves measuring and interpreting drug concentrations in blood plasma or serum to optimize pharmacotherapy. In psychiatry and neurology, TDM is a well-established tool for personalized drug treatments. The AGNP-TDM task force initially published guidelines for best practice TDM in 2004, 2011, and 2017. A fundamental methodological revision has now been carried out on how to determine therapeutic reference ranges and dose-related reference ranges transparently and systematically. In the current edition, 50 experts in neuropsychopharmacology offer a complete update of both ranges for each substance following an evidence-based approach. Various types of data were considered for reference range determination, ranging from meta-analyses to drug concentrations expected under recommended doses. Therapeutic reference ranges are now listed for 160 neuropsychiatric drugs, newly included for 30 drugs and revised for 88 drugs. Expected drug concentrations can be calculated based on a revised formula for 162 drugs. Obligatory TDM (i.e. for dose titration) is strongly recommended for 15 neuropsychiatric drugs and recommended for 39 drugs. TDM is classified as useful for 49 drugs and potentially useful for 62 drugs, indicating that it is recommended in specific clinical situations, such as suspected non-adherence, insufficient clinical response despite recommended doses, relapse during maintenance treatment, and many more. The 2026 update includes practical pharmacogenetic recommendations that are directly relevant to TDM. This work integrates a combination of strategies to guide drug treatments in clinical practice using all available tools. A consistent implementation of TDM and pharmacogenetic recommendations will enhance neuropsychopharmacotherapy, improve patient outcomes, and reduce healthcare costs.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":"166-295"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial.","authors":"Georgios Schoretsanitis, Stefan Unterecker, Xenia M Hart","doi":"10.1055/a-2897-5020","DOIUrl":"10.1055/a-2897-5020","url":null,"abstract":"","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":"164-165"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Drug Monitoring of Cannabinoids: Therapeutic Reference Ranges for Delta-9-tetrahydrocannabinol in Medical Cannabis, Nabiximols, Dronabinol and Nabilone.","authors":"Friederike Amann, Gudrun Hefner, Peter Cremer-Schaeffer, Gerhard Gründer, Winfried Häuser, Xenia M Hart, Frank Petzke, Gerald Zernig, Ursula Havemann-Reinecke","doi":"10.1055/a-2853-4984","DOIUrl":"https://doi.org/10.1055/a-2853-4984","url":null,"abstract":"<p><strong>Abstract: </strong>Medical cannabis, nabiximols, dronabinol and nabilone are used for various medical conditions. Despite their pronounced pharmacokinetic variability and complex concentration-effect relationships, therapeutic drug monitoring recommendations are lacking. We aimed to identify therapeutic reference ranges based on blood concentration-clinical effect relationships. Studies reporting blood concentrations and clinical effects/adverse effects or assessing cannabinoid receptors 1 and 2 occupancy were selected through a systematic literature search in the MEDLINE database via PubMed. Twenty-three articles were selected for vaporized/smoked medical cannabis, three for nabiximols, nine for dronabinol and one for nabilone. No article was identified for delta-9-tetrahydrocannabinol-dominant cannabis extracts. For vaporized/smoked medical cannabis, an orienting therapeutic reference range of 15-30 ng/mL delta-9-tetrahydrocannabinol was identified for pain reduction in diabetic peripheral neuropathy, while concentrations of <20 ng/mL delta-9-tetrahydrocannabinol were significantly correlated with intraocular pressure reduction and 7.5-10 ng/mL with improvement of tic symptoms. Half-maximum effective concentrations of 7-29 ng/mL delta-9-tetrahydrocannabinol were reported for \"high\" effects. For nabiximols, a preliminary therapeutic reference range of 1-10 ng/mL delta-9-tetrahydrocannabinol was determined for treating neuropathic pain and spasticity in adults with multiple sclerosis. For chemotherapy-induced nausea and vomiting, a preliminary therapeutic reference range of 1-5 ng/mL for nabilone and 5-15 ng/mL delta-9-tetrahydrocannabinol for dronabinol was assessed. In conclusion, relatively low concentrations may be sufficient to achieve therapeutic effects across all substances studied, with medical cannabis demonstrating these effects at lower concentrations than typically observed in recreational use. Nevertheless, adverse effects at therapeutic reference ranges cannot be excluded.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Naturalistic Study on the Cost Reduction and Efficacy of Long-acting Antipsychotics in an Early Intervention Programme for Patients with Recent-onset Psychosis.","authors":"MariaJose Acuña, Joaquin-Carlos Martin-Muñoz, María-Jesús Muñoz, Francisco-Dionisio Casado, Matilde Blanco-Venzalá, Luisa Rosado-Tejero, Eva Utrera-Caballero, Juan-José Galafate","doi":"10.1055/a-2865-3839","DOIUrl":"https://doi.org/10.1055/a-2865-3839","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the impact of treatment with long-acting injectable antipsychotics on direct healthcare costs in a programme for patients with recent-onset psychosis.</p><p><strong>Methods: </strong>This was an observational, retrospective study. We included all patients admitted to the programme (from July 2015 to April 2020). All costs were recorded and three groups were compared: those receiving oral antipsychotics; those receiving oral treatment initially but subsequently switching before long-acting injectable antipsychotics; and those receiving after long-acting injectable antipsychotics.</p><p><strong>Results: </strong>A total of 136 patients were included: 68 patients in the oral antipsychotics group and 34 patients in each of the other two groups. The average total healthcare cost per person/y was €11,347 in the oral antipsychotics group, €49,001 in the before long-acting injectable antipsychotics group, and €27,170 in the after long-acting injectable antipsychotics group. The comparisons between the first group and the other two were significant and between the after long-acting injectable antipsychotics vs before long-acting injectable antipsychotics groups (<i>p</i><0.01, Mann-Whitney <i>U</i> test). These differences were related to the costs of psychiatric admissions, with an average per person/y of €2,252 (oral antipsychotics group), €22,947 (before long-acting injectable antipsychotics group) and only €777 in the after long-acting injectable antipsychotics group. The only prior clinical or demographic distinction between the three groups was the presence of substance abuse disorder, 41.2% in the oral treatment group vs. 70.6% in the long-acting injectable antipsychotics group (<i>p</i>=0.003 <i>X</i> ² Pearson 99%; confidence interval: 0.002-0.005). In patients with recent-onset psychosis and comorbid substance abuse disorder, treatment with long-acting injectable antipsychotics, despite the higher cost of this medication, may be associated with a reduction in total direct healthcare costs. In our study, it saves €21,831 per patient/y.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Clozapine Serum Levels Do Not Improve Response: An Observational Study in Patients with Schizophrenia Treated with Clozapine in a Naturalistic Setting.","authors":"Xenia M Hart, Dusan Hirjak, Chin B Eap, Luzie Eichentopf, Stefan Fritze, Xenija Marie Lense, Dennis Scharf, Claudia Schilling, Nina Schwind, Philip Post, Katja Wesner, Gerhard Gründer","doi":"10.1055/a-2868-3000","DOIUrl":"https://doi.org/10.1055/a-2868-3000","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Clozapine is an effective antipsychotic used in treatment-resistant schizophrenia, but high serum levels may increase side effects. This study aimed to examine the efficacy and tolerability profile of clozapine in a naturalistic setting. The impact of multiple factors, specifically CYP1A2 genotypes, smoking, and fluvoxamine coadministration, on CYP1A2 enzyme activity was assessed as a secondary exploratory end point.</p><p><strong>Study design: </strong>In this prospective, observational study, 32 patients receiving stable clozapine therapy were observed over a 24-hour period at the Central Institute for Mental Health, Mannheim. Clozapine blood levels were measured via liquid chromatography-mass spectrometry and the MyCare Clozapine Assay.</p><p><strong>Results: </strong>Clozapine levels above 600 ng/mL were not associated with increased clinical efficacy but were linked to more side effects. Sleep quality was generally poor, and daytime sedation was frequent. While coadministration with the CYP1A2 inhibitor fluvoxamine led to a dose-corrected increase in clozapine levels of approximately 50%; smoking reduced clozapine (-36%) and norclozapine (-32%) levels.</p><p><strong>Conclusions: </strong>Clozapine levels above the therapeutic reference range may not provide additional benefits and could increase side effects. Therapeutic drug monitoring is an essential clinical practice tool, especially when using comedication or in smokers. Overall, these findings should be interpreted as exploratory and supportive of existing therapeutic guidance because of the small sample size and naturalistic study design.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rates of Hypoprolactinemia in Bipolar Patients Receiving Once-monthly Long-acting Injectable Aripiprazole.","authors":"Fatma Simsek","doi":"10.1055/a-2861-6690","DOIUrl":"https://doi.org/10.1055/a-2861-6690","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoprolactinemia, an often overlooked condition in psychiatric practice, has been suggested to be associated with potential adverse effects on sexual and metabolic functions, similar to those reported in hyperprolactinemia. Recently, numerous studies have indicated that oral aripiprazole can lead to hypoprolactinemia in patients with various psychiatric disorders. However, the frequency and severity of hypoprolactinemia in bipolar patients receiving a 400-mg dose of once-monthly long-acting injectable aripiprazole remain unknown. This study aimed to assess the effects of once-monthly long-acting (400 mg) injectable aripiprazole on prolactin levels in patients with bipolar disorder.</p><p><strong>Methods: </strong>Fifty patients with bipolar disorder (25 women and 25 men) receiving the 400-mg dose of once-monthly long-acting injectable aripiprazole, either as monotherapy or in combination with other psychiatric medications, were recruited for this study.</p><p><strong>Results: </strong>Overall, the rate of hypoprolactinemia was 52% among the study participants. When stratified by sex, the prevalence was 68% in men and 36% in women. In addition, 28% of male patients and 4% of female patients had serum prolactin levels below 1 ng/mL. Mean serum prolactin levels were significantly higher in women than in men (<i>z</i>=- 3.435, <i>p</i>=0.001). No significant correlation was observed between serum prolactin concentrations and age or treatment duration in either sex.</p><p><strong>Discussion: </strong>Once-monthly injectable aripiprazole treatment in bipolar disorder was associated with a relatively high prevalence of hypoprolactinemia in both female and male patients. Given emerging evidence of potential metabolic and sexual effects of hypoprolactinemia, monitoring prolactin levels may be clinically relevant in patients receiving injectable aripiprazole.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Be Aware of AI Limitations.","authors":"Scott Monteith, Tasha Glenn, John Richard Geddes, Peter C Whybrow, Eric Achtyes, Rita Bauer, Michael Bauer","doi":"10.1055/a-2743-2564","DOIUrl":"10.1055/a-2743-2564","url":null,"abstract":"","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":"157-158"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Escitalopram and Clonazepam Affect Gasotransmitter-related Enzyme (nNOS, HO-2, CBS) Gene Expression in the Rat Brain.","authors":"Artur Pałasz, Maria Sygidus, Antonello Pinna, Aleksandra Suszka-Świtek, Katarzyna Bogus, Aneta Piwowarczyk-Nowak, Veerta Sharma, Marek Krzystanek, Itiana Castro Menezes-Pazini, Łukasz Filipczyk","doi":"10.1055/a-2894-2668","DOIUrl":"10.1055/a-2894-2668","url":null,"abstract":"","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":"59 3","pages":"e2"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing Machine Learning to Forecast 3-Month Remission Outcomes in Bipolar Disorder Patients Treated with Lithium.","authors":"Alessandro Cuomo, Despoina Koukouna, Simone Pardossi, Mario Pinzi, Caterina Pierini, Maria Beatrice Rescalli, Andrea Fagiolini","doi":"10.1055/a-2751-7163","DOIUrl":"10.1055/a-2751-7163","url":null,"abstract":"<p><strong>Introduction: </strong>Lithium remains a first-line mood stabilizer for bipolar disorder; yet, only a subset of patients achieves symptomatic remission. Early prediction of treatment response could guide personalized management. In this study, we leveraged machine learning algorithms to predict 3-month remission, defined as a Montgomery-Åsberg Depression Rating Scale score≤10, in 593 patients with bipolar disorder initiating lithium.</p><p><strong>Methods: </strong>In this retrospective cohort, baseline sociodemographic, clinical and laboratory data as well as concomitant medication usage were collected. Montgomery Åsberg Depression Rating Scale and Mania Rating Scale were administered at baseline and 3 months. Data were preprocessed (missing imputation and normalization) and then split into 80% training and 20% test sets. We evaluated various machine learning techniques such as random forest, XGBoost, neural network and support vector machines with five-fold cross validation. Performance metrics included area under the receiver operating characteristic curve and accuracy.</p><p><strong>Results: </strong>The mean age was 44±16.9 years and 53% of participants were females. The remission rate at 3 months was 44%. The random forest model (augmented by polynomial transformations) performed best (area under the receiver operating characteristic curve=0.76 and accuracy=0.64) improving by 10% of the standard logistic model. Key predictors included the baseline Montgomery Åsberg Depression Rating Scale and Mania Rating Scale, creatinine, thyroid-stimulating hormone levels, body mass index and age.</p><p><strong>Discussion: </strong>Machine learning, particularly gradient boosted trees, can help to predict the 3-month remission in bipolar disorder patients who start lithium therapy. Incorporating clinical and laboratory features enhances the early identification of likely responders, enabling personalized treatment strategies.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":"129-136"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Drug Discovery and Development: Raising Quality per Decision.","authors":"Shota Furukawa, Hiroyuki Uchida, Taishiro Kishimoto","doi":"10.1055/a-2810-8972","DOIUrl":"10.1055/a-2810-8972","url":null,"abstract":"<p><strong>Abstract: </strong>Drug research and development continuously encounters prolonged timelines, escalating costs, and high attrition rates. In this narrative review, we integrated recent advances in artificial intelligence across target identification, drug repurposing, de novo molecular design, structural biology, safety prediction, and artificial intelligence-supported clinical development, aligning these innovations with evolving global regulatory frameworks. Predictive and interpretable artificial intelligence could enhance the quality of decision-making throughout the research and development process when combined with causal or mechanistic priors, synthesis-aware and physics-informed molecular design, external validation with clear applicability domains, and governance systems aligned with multiple regulatory guidelines and qualified digital endpoint applications. Case studies of artificial intelligence-assisted discovery and repurposing demonstrate shorter development timelines, improved compound quality, and higher-level early-phase success, while underscoring challenges such as overfitting, model generalizability, and dataset bias. Establishing a context-of-use-based \"credibility plan\" and adopting equity-by-design through the inclusion of non-European datasets and subgroup performance evaluation are essential for achieving generalizable impact. Artificial intelligence integration with new approach methodologies and adaptive or covariate-adjusted clinical trials may help reduce development inefficiency without compromising scientific or ethical rigor.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":"103-116"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}