Pub Date : 2026-02-06DOI: 10.1016/j.euroneuro.2026.112783
Christoffer Brynte, Arnt Schellekens, Maija Konstenius, Alex Hendrikus Abraham Begeman, Cleo Lina Crunelle, Zsolt Demetrovics, Geert Dom, Romain Icick, Brian Johnson, Máté Kapitány-Fövény, Frances R Levin, Mathias Luderer, Frieda Matthys, Franz Moggi, Raul Felipe Palma-Álvarez, J Antoni Ramos-Quiroga, Andreas Reif, Michiel W van Kernebeek, María C Vélez-Pastrana, Wim van den Brink, Johan Franck
Comorbid attention deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) is associated with poor treatment outcomes. This international multi-center observational prospective cohort study aimed to gain knowledge about predictors of treatment outcomes in adult SUD+ADHD patients. Data was collected from June 2017 to May 2021 at baseline, four weeks, three months, and nine months at twelve treatment services in nine countries. Main outcomes were: Treatment retention, ≥30% reduction from baseline to follow-up according to the adult ADHD self-report scale (ASRS-18), and self-reported substance use at three-month follow-up. A total of 137 adult females (24 %) and 441 adult males (76 %) were enrolled. Receiving stimulant treatment for ADHD was significantly associated with better treatment retention (OR: 2·4, 95% CI: 1·4-4·2), ≥30% reduction in ASRS total score (OR: 2·6, 95% CI: 1·2-6·1), and fewer heavy drinking days (IRR: 0·24, 95% CI: 0·13-0·42) at three months. Psychosocial treatment for ADHD was independently and significantly associated with fewer heavy drinking days at three months (IRR: 0·27, 95% CI: 0·14-0·51). In summary, treatment of ADHD in SUD+ADHD patients was related to improvements in ADHD-symptoms, treatment retention and fewer heavy drinking days at follow-up. These findings highlight the importance of ADHD treatment provision in this population. Future RCTs are warranted to confirm these results and should assess combinations of ADHD treatments and SUD treatments using different doses of stimulants. Trial Registration: ISRCTN (https://doi.org/10.1186/ISRCTN15998989).
{"title":"Predictors of treatment success in patients with substance use disorder (SUD) and co-morbid attention deficit/hyperactivity disorder (ADHD): Results from the International Naturalistic Cohort Study of ADHD and SUD (INCAS).","authors":"Christoffer Brynte, Arnt Schellekens, Maija Konstenius, Alex Hendrikus Abraham Begeman, Cleo Lina Crunelle, Zsolt Demetrovics, Geert Dom, Romain Icick, Brian Johnson, Máté Kapitány-Fövény, Frances R Levin, Mathias Luderer, Frieda Matthys, Franz Moggi, Raul Felipe Palma-Álvarez, J Antoni Ramos-Quiroga, Andreas Reif, Michiel W van Kernebeek, María C Vélez-Pastrana, Wim van den Brink, Johan Franck","doi":"10.1016/j.euroneuro.2026.112783","DOIUrl":"https://doi.org/10.1016/j.euroneuro.2026.112783","url":null,"abstract":"<p><p>Comorbid attention deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) is associated with poor treatment outcomes. This international multi-center observational prospective cohort study aimed to gain knowledge about predictors of treatment outcomes in adult SUD+ADHD patients. Data was collected from June 2017 to May 2021 at baseline, four weeks, three months, and nine months at twelve treatment services in nine countries. Main outcomes were: Treatment retention, ≥30% reduction from baseline to follow-up according to the adult ADHD self-report scale (ASRS-18), and self-reported substance use at three-month follow-up. A total of 137 adult females (24 %) and 441 adult males (76 %) were enrolled. Receiving stimulant treatment for ADHD was significantly associated with better treatment retention (OR: 2·4, 95% CI: 1·4-4·2), ≥30% reduction in ASRS total score (OR: 2·6, 95% CI: 1·2-6·1), and fewer heavy drinking days (IRR: 0·24, 95% CI: 0·13-0·42) at three months. Psychosocial treatment for ADHD was independently and significantly associated with fewer heavy drinking days at three months (IRR: 0·27, 95% CI: 0·14-0·51). In summary, treatment of ADHD in SUD+ADHD patients was related to improvements in ADHD-symptoms, treatment retention and fewer heavy drinking days at follow-up. These findings highlight the importance of ADHD treatment provision in this population. Future RCTs are warranted to confirm these results and should assess combinations of ADHD treatments and SUD treatments using different doses of stimulants. Trial Registration: ISRCTN (https://doi.org/10.1186/ISRCTN15998989).</p>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"106 ","pages":"112783"},"PeriodicalIF":6.7,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1016/j.euroneuro.2026.112781
Hailun Xia, Yuanyi Yang
{"title":"Comment on “All-cause and cause-specific mortality in people with mental disorders: a population-based study on risk evaluation, effect modifiers and excess life-years lost in Hong Kong”","authors":"Hailun Xia, Yuanyi Yang","doi":"10.1016/j.euroneuro.2026.112781","DOIUrl":"10.1016/j.euroneuro.2026.112781","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"106 ","pages":"Article 112781"},"PeriodicalIF":6.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.euroneuro.2026.112780
Emma Pruin , Meike Bartels , Ernest Diez Benavente , Noortje A.M. van den Dungen , Joost K.R. Hoekstra , Dominique D.P. de Kleijn , Lennart P.L. Landsmeer , Michal Mokry , Gerard Pasterkamp , Brenda W.J.H. Penninx , Wouter J. Peyrot , Hester M. den Ruijter , Sander W. van der Laan , Yuri Milaneschi
The increased risk of atherosclerotic diseases (stroke, coronary artery disease [CAD]) observed in depression may stem from shared pathophysiology. We examined whether: 1) major depression (MD) and atherosclerotic traits share genetic risk, and 2) altered gene expression in various tissues linked to shared genetics has a potential causal role in depression etiology. Data from the largest genome-wide association studies of MD (N = 3,887,532) and 8 atherosclerotic traits (N = 26,909–1,308,460) were used in Two-Sample Mendelian randomization and colocalization to detect cross-trait causal associations and genomic loci containing shared causal variants. In shared loci, summary data-based Mendelian randomization estimated the effects of gene expression on MD etiology using expression quantitative trait loci datasets from whole blood, brain and heart tissues and atherosclerotic plaques from the Athero-Express Biobank Study. MD genetic liability increased risk of any stroke (OR=1.15, p = 9.47 × 10–8), ischemic stroke (OR=1.16, p = 1.52 × 10–7), small vessel disease (OR=1.34, p = 4.76 × 10–5) and CAD (OR=1.2, 95 %CIs=1.13–1.26, p = 3.76 × 10–22). Eight genomic regions harbored potentially shared causal variants, including one on chromosome 7 linking MD with any stroke, ischemic stroke and CAD. Altered expression of 16 genes in blood, 10 in brain, and 6 in heart was found causal for MD etiology. In atherosclerotic plaques, one gene was linked to MD at nominal significance only. Major depression and atherosclerotic diseases share genetic risk potentially acting in depression pathophysiology through expression of genes in blood, brain and heart tissues. Involvement of atherosclerotic plaques in depression etiology was not supported. Identified pathways could guide the development of new treatments to prevent depression-heightened atherosclerotic risk.
在抑郁症中观察到的动脉粥样硬化性疾病（中风、冠状动脉疾病[CAD]）的风险增加可能源于共同的病理生理。我们研究了：1)重度抑郁症（MD）和动脉粥样硬化特征是否具有共同的遗传风险，以及2)与共同遗传相关的各种组织中基因表达的改变在抑郁症病因学中是否具有潜在的因果作用。来自MD （N = 3,887,532）和8个动脉粥样硬化特征（N = 26,909-1,308,460）的最大全基因组关联研究的数据被用于双样本孟德尔随机化和共定位，以检测跨性状因果关联和包含共享因果变异的基因组位点。在共享基因座中，基于汇总数据的孟德尔随机化评估了基因表达对MD病因学的影响，使用来自Athero-Express Biobank研究的全血、脑和心脏组织以及动脉粥样硬化斑块的表达数量性状基因座数据集。MD遗传倾向增加任何中风（OR=1.15, p = 9.47 × 10-8）、缺血性中风（OR=1.16, p = 1.52 × 10-7）、小血管疾病（OR=1.34, p = 4.76 × 10-5）和CAD （OR=1.2, 95% ci = 1.13-1.26, p = 3.76 × 10-22）的风险。8个基因组区域可能存在共同的因果变异，包括7号染色体上的一个将MD与任何中风、缺血性中风和CAD联系起来。血液中有16个基因表达改变，大脑中有10个基因表达改变，心脏中有6个基因表达改变。在动脉粥样硬化斑块中，一个基因与MD的关联仅具有名义意义。重度抑郁症和动脉粥样硬化性疾病通过在血液、大脑和心脏组织中表达基因，在抑郁症病理生理中具有潜在的遗传风险。不支持动脉粥样硬化斑块在抑郁症病因中的作用。确定的途径可以指导新的治疗方法的发展，以防止抑郁症增加动脉粥样硬化的风险。
{"title":"Major depression and atherosclerotic disease: Linking shared genetics to pathways in blood, brain, heart, and atherosclerotic plaques","authors":"Emma Pruin , Meike Bartels , Ernest Diez Benavente , Noortje A.M. van den Dungen , Joost K.R. Hoekstra , Dominique D.P. de Kleijn , Lennart P.L. Landsmeer , Michal Mokry , Gerard Pasterkamp , Brenda W.J.H. Penninx , Wouter J. Peyrot , Hester M. den Ruijter , Sander W. van der Laan , Yuri Milaneschi","doi":"10.1016/j.euroneuro.2026.112780","DOIUrl":"10.1016/j.euroneuro.2026.112780","url":null,"abstract":"<div><div>The increased risk of atherosclerotic diseases (stroke, coronary artery disease [CAD]) observed in depression may stem from shared pathophysiology. We examined whether: 1) major depression (MD) and atherosclerotic traits share genetic risk, and 2) altered gene expression in various tissues linked to shared genetics has a potential causal role in depression etiology. Data from the largest genome-wide association studies of MD (<em>N</em> = 3,887,532) and 8 atherosclerotic traits (<em>N</em> = 26,909–1,308,460) were used in Two-Sample Mendelian randomization and colocalization to detect cross-trait causal associations and genomic loci containing shared causal variants. In shared loci, summary data-based Mendelian randomization estimated the effects of gene expression on MD etiology using expression quantitative trait loci datasets from whole blood, brain and heart tissues and atherosclerotic plaques from the Athero-Express Biobank Study. MD genetic liability increased risk of any stroke (OR=1.15, <em>p</em> = 9.47 × 10<sup>–8</sup>), ischemic stroke (OR=1.16, <em>p</em> = 1.52 × 10<sup>–7</sup>), small vessel disease (OR=1.34, <em>p</em> = 4.76 × 10<sup>–5</sup>) and CAD (OR=1.2, 95 %CIs=1.13–1.26, <em>p</em> = 3.76 × 10<sup>–22</sup>). Eight genomic regions harbored potentially shared causal variants, including one on chromosome 7 linking MD with any stroke, ischemic stroke and CAD. Altered expression of 16 genes in blood, 10 in brain, and 6 in heart was found causal for MD etiology. In atherosclerotic plaques, one gene was linked to MD at nominal significance only. Major depression and atherosclerotic diseases share genetic risk potentially acting in depression pathophysiology through expression of genes in blood, brain and heart tissues. Involvement of atherosclerotic plaques in depression etiology was not supported. Identified pathways could guide the development of new treatments to prevent depression-heightened atherosclerotic risk.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"106 ","pages":"Article 112780"},"PeriodicalIF":6.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.euroneuro.2026.112771
Mark E. Schmidt , Cynthia Gargano , Xianhuang Zhou , James A. Palmer , Ziad S. Saad , Eduard Vieta , Wayne C. Drevets , Kim Stuyckens , Gahan Pandina
JNJ-42165279 is a potent, selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of the endocannabinoid N-arachidonoylethanolamide (anandamide), which plays a role in regulation of fear and anxiety responses. This double-blind, randomised, placebo-controlled, phase 2a study assessed the efficacy, safety and pharmacodynamics of adjunctive treatment with JNJ-42165279 in participants with major depressive disorder (MDD) with anxious distress and inadequate response to selective serotonin reuptake inhibitors (SSRI) or serotonergic/noradrenergic reuptake inhibitors (SNRI). Eligible participants (18-64 years; N = 153) were randomised (1:1) to receive JNJ-42165279 (25 mg) or placebo orally once daily and were maintained on their current SSRI/SNRI treatment. The primary endpoint was the change from baseline at week 6 in the 17-item Hamilton Depression Rating Scale (HDRS17). The study results did not show a significant treatment effect of adjunctive JNJ-42165279 on the primary endpoint versus placebo (least square mean difference [standard error]: ˗0.2 [1.04]; one-sided p=0.416) in the enriched intent-to-treat population. Findings for the key secondary efficacy endpoints also did not demonstrate an additional benefit of adjunctive JNJ-42165279 treatment over placebo. Treatment with JNJ-42165279 produced substantial increases in the mean concentrations of fatty acid amides in plasma, and the plasma JNJ-42165279 and anandamide levels were strongly correlated. The safety results were consistent with the known safety profile of JNJ-42165279. Overall, adjunctive treatment with JNJ-42165279 at the dose tested did not provide significant benefit in reducing depression/anxiety symptoms versus placebo but showed no new safety signals in participants with MDD and anxious distress.
{"title":"Efficacy and safety of adjunctive treatment with the fatty acid amide hydrolase inhibitor JNJ-42165279 in participants with major depressive disorder with anxious distress: A double-blind, placebo-controlled, randomised study","authors":"Mark E. Schmidt , Cynthia Gargano , Xianhuang Zhou , James A. Palmer , Ziad S. Saad , Eduard Vieta , Wayne C. Drevets , Kim Stuyckens , Gahan Pandina","doi":"10.1016/j.euroneuro.2026.112771","DOIUrl":"10.1016/j.euroneuro.2026.112771","url":null,"abstract":"<div><div>JNJ-42165279 is a potent, selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of the endocannabinoid N-arachidonoylethanolamide (anandamide), which plays a role in regulation of fear and anxiety responses. This double-blind, randomised, placebo-controlled, phase 2a study assessed the efficacy, safety and pharmacodynamics of adjunctive treatment with JNJ-42165279 in participants with major depressive disorder (MDD) with anxious distress and inadequate response to selective serotonin reuptake inhibitors (SSRI) or serotonergic/noradrenergic reuptake inhibitors (SNRI). Eligible participants (18-64 years; <em>N</em> = 153) were randomised (1:1) to receive JNJ-42165279 (25 mg) or placebo orally once daily and were maintained on their current SSRI/SNRI treatment. The primary endpoint was the change from baseline at week 6 in the 17-item Hamilton Depression Rating Scale (HDRS<sub>17</sub>). The study results did not show a significant treatment effect of adjunctive JNJ-42165279 on the primary endpoint versus placebo (least square mean difference [standard error]: ˗0.2 [1.04]; one-sided p=0.416) in the enriched intent-to-treat population. Findings for the key secondary efficacy endpoints also did not demonstrate an additional benefit of adjunctive JNJ-42165279 treatment over placebo. Treatment with JNJ-42165279 produced substantial increases in the mean concentrations of fatty acid amides in plasma, and the plasma JNJ-42165279 and anandamide levels were strongly correlated. The safety results were consistent with the known safety profile of JNJ-42165279. Overall, adjunctive treatment with JNJ-42165279 at the dose tested did not provide significant benefit in reducing depression/anxiety symptoms versus placebo but showed no new safety signals in participants with MDD and anxious distress.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"106 ","pages":"Article 112771"},"PeriodicalIF":6.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1016/j.euroneuro.2026.112767
Agampodi Ishan De Zoysa , Janani Govinnage , Frank Giorlando , Seetal Dodd , JC Narayanaswamy , Michael Berk
Despite significant advancements in psychopharmacology, there are inadequate treatment options for many psychiatric disorders, including major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorders. This review explores emerging neurobiological targets beyond conventional monoaminergic approaches, focusing on sodium channels, Neuropeptide Y (NPY), Neurokinin 1 (NK1) receptors, P2 × 7 purinergic receptors, Sigma-1 receptors, and Orexin. Recent evidence suggests that sodium channel modulators, such as evenamide, may offer therapeutic benefits for treatment-resistant schizophrenia by stabilizing glutamatergic neurotransmission. NPY-based therapies have potential in stress-related disorders, foreshadowing rapid anxiolytic and antidepressant effects through modulation of the stress response. NK1 receptor antagonists, although inconsistent in mood disorders, show promise in addiction treatment by reducing substance cravings. The P2 × 7 receptor, a key regulator of neuroinflammation, has been implicated in mood disorders, and its pharmacological inhibition may provide neuroprotective benefits. Additionally, Sigma-1 receptor agonists, including Blarcamesine and Pridopidine, have shown neuroprotective and cognitive-enhancing properties, making them attractive candidates for psychiatric and neurodegenerative disorders. Orexin receptor antagonists, such as suvorexant and seltorexant, have potential in mood disorders and substance dependence, highlighting the broader therapeutic applications of targeting the orexinergic system. While these emerging therapeutic targets hold promise, challenges remain in translating preclinical findings into effective clinical applications. Large-scale, placebo-controlled trials are necessary to establish their efficacy and safety. The identification of biomarkers for patient stratification will be critical in the hitherto elusive goal of developing precision medicine approaches. Targeted pharmacological interventions offer a path toward more effective, well-tolerated, and potentially individualized treatment options for patients with severe mental illness.
{"title":"Emerging neurobiological targets in psychiatric treatment","authors":"Agampodi Ishan De Zoysa , Janani Govinnage , Frank Giorlando , Seetal Dodd , JC Narayanaswamy , Michael Berk","doi":"10.1016/j.euroneuro.2026.112767","DOIUrl":"10.1016/j.euroneuro.2026.112767","url":null,"abstract":"<div><div>Despite significant advancements in psychopharmacology, there are inadequate treatment options for many psychiatric disorders, including major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorders. This review explores emerging neurobiological targets beyond conventional monoaminergic approaches, focusing on sodium channels, Neuropeptide Y (NPY), Neurokinin 1 (NK1) receptors, P2 × 7 purinergic receptors, Sigma-1 receptors, and Orexin. Recent evidence suggests that sodium channel modulators, such as evenamide, may offer therapeutic benefits for treatment-resistant schizophrenia by stabilizing glutamatergic neurotransmission. NPY-based therapies have potential in stress-related disorders, foreshadowing rapid anxiolytic and antidepressant effects through modulation of the stress response. NK1 receptor antagonists, although inconsistent in mood disorders, show promise in addiction treatment by reducing substance cravings. The P2 × 7 receptor, a key regulator of neuroinflammation, has been implicated in mood disorders, and its pharmacological inhibition may provide neuroprotective benefits. Additionally, Sigma-1 receptor agonists, including Blarcamesine and Pridopidine, have shown neuroprotective and cognitive-enhancing properties, making them attractive candidates for psychiatric and neurodegenerative disorders. Orexin receptor antagonists, such as suvorexant and seltorexant, have potential in mood disorders and substance dependence, highlighting the broader therapeutic applications of targeting the orexinergic system. While these emerging therapeutic targets hold promise, challenges remain in translating preclinical findings into effective clinical applications. Large-scale, placebo-controlled trials are necessary to establish their efficacy and safety. The identification of biomarkers for patient stratification will be critical in the hitherto elusive goal of developing precision medicine approaches. Targeted pharmacological interventions offer a path toward more effective, well-tolerated, and potentially individualized treatment options for patients with severe mental illness.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"105 ","pages":"Article 112767"},"PeriodicalIF":6.7,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.euroneuro.2026.112768
Iryna Frankova , Iryna Leshchuk
{"title":"Traumatic loss, bereavement, and prolonged grief disorder in times of war: insights from Ukraine","authors":"Iryna Frankova , Iryna Leshchuk","doi":"10.1016/j.euroneuro.2026.112768","DOIUrl":"10.1016/j.euroneuro.2026.112768","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"106 ","pages":"Article 112768"},"PeriodicalIF":6.7,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.euroneuro.2026.112769
Yinzhao Liu , Iris E Sommer , Georgios Schoretsanitis , Iris Hamers , Toon A W Scheurink , Marieke J H Begemann , Shiral S Gangadin , Nico J M van Beveren
The clinical evidence for antipsychotic (AP) therapeutic drug monitoring (TDM) in evaluating AP-related movement disorders and cardiometabolic side-effects remains inconsistent. This study evaluates how AP plasma concentrations associate with movement disorders and cardiometabolic side-effects over time, and compares its predictive value to prescription dose in first-episode psychosis (FEP) patients. We included 200 remitted FEP patients from the HAMLETT trial. AP plasma concentrations were standardized using robust z-scores to accommodate different AP types. The St. Hans Rating Scale and Barnes Akathisia Rating Scale assessed movement disorders. Cardiometabolic indices included body mass index, waist circumference, blood pressure, glucose, triglycerides, and cholesterol. We evaluated longitudinal associations between plasma concentrations, movement disorders and cardiometabolic side-effects using two-part and linear mixed-effects models, and compared its predictive value to prescription dose using Bayesian Information Criterion (ΔBIC). Over a median 6-month follow-up (range = 0–48), AP plasma concentrations were positively associated with odds for parkinsonism (OR = 1.81, 95 % CI 1.27, 2.57, p = 0.001). No associations were found with tardive dyskinesia, akathisia, tardive dystonia, or cardiometabolic indices. AP plasma concentrations predicted parkinsonism better than prescription dose (ΔBIC = -2.95), but showed lower predictive value for waist circumference (ΔBIC = 3.22), total cholesterol (ΔBIC = 3.70), low-density-lipoprotein cholesterol (ΔBIC = 2.14) and non-high-density-lipoprotein cholesterol (ΔBIC = 5.46). These findings suggest that in remitted FEP patients, AP TDM may be more useful than dose in evaluating parkinsonism, likely because plasma concentrations more closely reflect free drugs at striatal dopamine receptors, but it does not appear useful for cardiometabolic side-effects.
{"title":"Antipsychotic plasma concentration as predictor of movement disorders and cardiometabolic side-effects: A comparison with prescription dose","authors":"Yinzhao Liu , Iris E Sommer , Georgios Schoretsanitis , Iris Hamers , Toon A W Scheurink , Marieke J H Begemann , Shiral S Gangadin , Nico J M van Beveren","doi":"10.1016/j.euroneuro.2026.112769","DOIUrl":"10.1016/j.euroneuro.2026.112769","url":null,"abstract":"<div><div>The clinical evidence for antipsychotic (AP) therapeutic drug monitoring (TDM) in evaluating AP-related movement disorders and cardiometabolic side-effects remains inconsistent. This study evaluates how AP plasma concentrations associate with movement disorders and cardiometabolic side-effects over time, and compares its predictive value to prescription dose in first-episode psychosis (FEP) patients. We included 200 remitted FEP patients from the HAMLETT trial. AP plasma concentrations were standardized using robust z-scores to accommodate different AP types. The St. Hans Rating Scale and Barnes Akathisia Rating Scale assessed movement disorders. Cardiometabolic indices included body mass index, waist circumference, blood pressure, glucose, triglycerides, and cholesterol. We evaluated longitudinal associations between plasma concentrations, movement disorders and cardiometabolic side-effects using two-part and linear mixed-effects models, and compared its predictive value to prescription dose using Bayesian Information Criterion (ΔBIC). Over a median 6-month follow-up (range = 0–48), AP plasma concentrations were positively associated with odds for parkinsonism (OR = 1.81, 95 % CI 1.27, 2.57, <em>p</em> = 0.001). No associations were found with tardive dyskinesia, akathisia, tardive dystonia, or cardiometabolic indices. AP plasma concentrations predicted parkinsonism better than prescription dose (ΔBIC = -2.95), but showed lower predictive value for waist circumference (ΔBIC = 3.22), total cholesterol (ΔBIC = 3.70), low-density-lipoprotein cholesterol (ΔBIC = 2.14) and non-high-density-lipoprotein cholesterol (ΔBIC = 5.46). These findings suggest that in remitted FEP patients, AP TDM may be more useful than dose in evaluating parkinsonism, likely because plasma concentrations more closely reflect free drugs at striatal dopamine receptors, but it does not appear useful for cardiometabolic side-effects.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"105 ","pages":"Article 112769"},"PeriodicalIF":6.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.euroneuro.2026.112766
Ting-Hui Liu , Chih-Cheng Lai
{"title":"Response to the letter regarding \"risk of manic switch and suicidal outcomes in bipolar depression treated with esketamine\"","authors":"Ting-Hui Liu , Chih-Cheng Lai","doi":"10.1016/j.euroneuro.2026.112766","DOIUrl":"10.1016/j.euroneuro.2026.112766","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"106 ","pages":"Article 112766"},"PeriodicalIF":6.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146006813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-17DOI: 10.1016/j.euroneuro.2026.112770
Yanlong Yao, Xu Fan
{"title":"Gene-environment interactions and white matter integrity in mood disorders: Further directions","authors":"Yanlong Yao, Xu Fan","doi":"10.1016/j.euroneuro.2026.112770","DOIUrl":"10.1016/j.euroneuro.2026.112770","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"105 ","pages":"Article 112770"},"PeriodicalIF":6.7,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号