Journal of Psychopharmacology最新文献

{"title":"Cognitive effects, pharmacokinetics, and safety of zuranolone administered alone or with alprazolam or ethanol in healthy adults in a phase 1 trial.","authors":"Joi Dunbar, David P Walling, Howard A Hassman, Rakesh Jain, Andy Czysz, Indrani Nandy, Victor Ona, Margaret K Moseley, Seth Levin, Paul Maruff","doi":"10.1177/02698811241282777","DOIUrl":"10.1177/02698811241282777","url":null,"abstract":"<p><strong>Background: </strong>Zuranolone is an oral, once-daily, 14-day treatment course approved for adults with postpartum depression in the United States.</p><p><strong>Aims: </strong>To assess cognitive effects, pharmacokinetics, and safety of zuranolone, alone or with alprazolam/ethanol.</p><p><strong>Methods: </strong>This was a phase 1, two-part, two-period, randomized, double-blind, placebo-controlled crossover trial. Participants received zuranolone 50 mg or placebo once daily for 9 days, and additionally received alprazolam (1 mg, Part A), ethanol (males: 0.7 g/kg; females: 0.6 g/kg, Part B), or corresponding placebo on days 1, 5, and 9. Within each part, participants received all treatment combinations. Cognition was assessed using a computerized test battery; pharmacokinetics and safety were also evaluated.</p><p><strong>Results: </strong>All participants (Part A, <i>N</i> = 24; Part B, <i>N</i> = 25) received ⩾1 dose of zuranolone/placebo. Compared to placebo, zuranolone produced small-to-moderate cognitive decline (Cohen's |<i>d</i>| = 0.126-0.76); effects were larger with alprazolam (Cohen's |<i>d</i>| = 0.523-0.93) and ethanol (Cohen's |<i>d</i>| = 0.345-0.88). Zuranolone coadministration with alprazolam (Cohen's |<i>d</i>| = 0.6-1.227) or ethanol (Cohen's |<i>d</i>| = 0.054-0.5) generally worsened cognitive decline when compared with zuranolone alone. Maximal pharmacodynamic effects occurred at approximately 5 h and were resolved by 12 h postbaseline. No pharmacokinetic interactions were observed. Incidence of adverse events was similar between groups; most events were mild or moderate in severity.</p><p><strong>Conclusion: </strong>A general small-to-moderate magnitude decline in cognition occurred with zuranolone alone. Coadministration with alprazolam/ethanol increased the magnitude, but not the duration, of effects compared with single-agent administration. Zuranolone prescribers and patients should be aware of the potential for increased central nervous system-depressant effects if coadministered with GABAergic active compounds such as alprazolam and ethanol.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1122-1136"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468382","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}

{"title":"High-dose Vitamin-B6 reduces sensory over-responsivity.","authors":"Rebekah O Cracknell, Teresa Tavassoli, David T Field","doi":"10.1177/02698811241271972","DOIUrl":"10.1177/02698811241271972","url":null,"abstract":"<p><strong>Background: </strong>Sensory reactivity differences are experienced by between 5% and 15% of the population, often taking the form of sensory over-responsivity (SOR), in which sensory stimuli are experienced as unusually intense and everyday function is affected. A potential mechanism underlying over-responsivity is an imbalance between neural excitation and inhibition in which inhibitory influences are relatively weakened. Therefore, interventions that boost neural inhibition or reduce neural excitation may reduce SOR; Vitamin-B6 is the coenzyme for the conversion of excitatory glutamate to inhibitory gamma-aminobutyric acid (GABA), and in animal models, it both increases the concentration of GABA and reduces glutamate.</p><p><strong>Aims: </strong>To discover whether taking a high dose of Vitamin-B6 reduces SOR and other aspects of sensory reactivity.</p><p><strong>Methods: </strong>We recruited 300 adults (249 females) from the general population who completed the Sensory Processing 3-Dimensions Scale (SP-3D) first at baseline, and again following randomisation to either 1 month's supplementation with 100 mg Vitamin-B6, or one of two control conditions (1000 µg Vitamin-B12 or placebo). To focus on individuals who experience SOR, we analysed the effects of supplementation only on individuals with high baseline SOR scores (above the 87th percentile).</p><p><strong>Results: </strong>In individuals with SOR at baseline, Vitamin-B6 selectively reduced SOR compared to both placebo and Vitamin-B12. We also found that Vitamin-B6 selectively reduced postural disorder in individuals with high scores on this subscale at baseline, but there were no effects on the four remaining SP-3D subscales.</p><p><strong>Conclusions: </strong>Clinical trials and mechanistic studies should now be conducted in autism, attention deficit hyperactivity disorder and other groups with SOR.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1147-1156"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046812","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}

{"title":"Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.","authors":"Haohao Zhu, Yucai Qu, Qin Zhou, Zhiqiang Du, Zhenhe Zhou, Ying Jiang","doi":"10.1177/02698811241282613","DOIUrl":"10.1177/02698811241282613","url":null,"abstract":"<p><strong>Objective: </strong>Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint.</p><p><strong>Methods: </strong>We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on <i>p</i>-value, OR (Odds Ratio), and 95% confidence interval (95% CI).</p><p><strong>Results: </strong>From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; <i>p</i> = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; <i>p</i> = 0.002), respectively. No significant causal relationship was found between aspirin and MD (<i>p</i> > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, <i>p</i> = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, <i>p</i> = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, <i>p</i> = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings.</p><p><strong>Conclusion: </strong>This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1137-1146"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348920","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":"Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys.","authors":"Dishary Sharmin, Daniela Rüedi-Bettschen, Laís F Berro, Jemma E Cook, Jaren A Reeves-Darby, Tanya Pareek, Md Yeunus Mian, Farjana Rashid, Lalit Golani, Eliseu da Cruz Moreira-Junior, Donna M Platt, James M Cook, James K Rowlett","doi":"10.1177/02698811241286760","DOIUrl":"10.1177/02698811241286760","url":null,"abstract":"<p><strong>Background: </strong>Benzodiazepines bind to γ-aminobutyric acid type A (GABA_A) receptor subtypes identified by different α subunits (i.e., α1GABA_A, α2GABA_A, α3GABA_A, and α5GABA_A). Sedative-motor effects of benzodiazepines are thought to involve α1GABA_A and α3GABA_A subtypes.</p><p><strong>Aims: </strong>We evaluated observable measures of sedative-motor effects and species-typical behaviors in monkeys following acute administration of novel GABAkines (positive allosteric modulators of GABA_A receptors), with varying degrees of selective efficacy at different GABA_A receptor subtypes. We predicted that the induction of sedative-motor effects would depend on the degree of α1GABA_A and α3GABA_A efficacy.</p><p><strong>Methods: </strong>Adult female rhesus monkeys (<i>N</i> = 4) were implanted with chronic indwelling i.v. catheters. Quantitative behavioral observation was conducted by trained observers following administration of multiple doses of the conventional benzodiazepine alprazolam and the GABAkines MP-III-80 (preferential efficacy at α2/α3/α5GABA_A subtypes), KRM-II-81, MP-III-24 (both with preferential efficacy for α2/α3GABA_A subtypes), and MP-III-22 (preferential potency and efficacy for α5GABA_A subtypes).</p><p><strong>Results: </strong>As with alprazolam, all GABAkines induced significant levels of mild sedation (\"rest/sleep posture\"). Deep sedation was observed with alprazolam, MP-III-80, and MP-III-22; motoric effects (observable ataxia) were obtained with alprazolam, KRM-II-81, and MP-III-22 only. Surprisingly, the order of potency for rest/sleep posture was significantly associated only with potency at α5GABA_A subtypes.</p><p><strong>Conclusions: </strong>GABAkines with preferential efficacy at α2/α3GABA_A and/or α5GABA_A subtypes engendered sedative-motor effects in monkeys, although only compounds with α5GABA_A activity engendered deep sedation. Moreover, the significant relationship between potency obtained with in vitro electrophysiology data and the rest/sleep posture measure suggests a role for the α5GABA_A subtype in this milder form of sedation.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1157-1169"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391349","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":"Clinical effects of CYP2D6 phenoconversion in patients with psychosis.","authors":"Emma Y De Brabander, Esmee Breddels, Therese van Amelsvoort, Roos van Westrhenen","doi":"10.1177/02698811241278844","DOIUrl":"10.1177/02698811241278844","url":null,"abstract":"<p><strong>Background: </strong>Pharmacogenetics is considered a promising avenue for improving treatment outcomes, yet evidence arguing for the use of pharmacogenetics in the treatment of psychotic disorders is mixed and clinical usefulness is under debate. Many patients with psychosis use multiple medications, which can alter the metabolic capacity of <i>CYP</i> enzymes, a process called phenoconversion. In clinical studies, treatment outcomes of drugs for psychosis management may have been influenced by phenoconversion.</p><p><strong>Aim: </strong>Here we evaluate the impact and predictive value of CYP2D6 phenoconversion in patients with psychotic disorders under pharmacological treatment.</p><p><strong>Method: </strong>Phenoconversion-corrected phenotype was determined by accounting for inhibitor strength. Phenoconversion-corrected and genotype-predicted phenotypes were compared in association with side effects, subjective well-being and symptom severity.</p><p><strong>Results: </strong>Phenoconversion led to a large increase in poor metabolizers (PMs; 17-82, 16% of sample), due to concomitant use of the serotonin reuptake inhibitors fluoxetine and paroxetine. Neither CYP2D6-predicted nor phenoconversion-corrected phenotype was robustly associated with outcome measures. Risperidone, however, was most affected by the <i>CYP2D6</i> genotype.</p><p><strong>Conclusion: </strong>Polypharmacy and phenoconversion were prevalent and accounted for a significant increase in PMs. CYP2D6 may play a limited role in side effects, symptoms and well-being measures. However, due to the high frequency of occurrence, phenoconversion should be considered in future clinical trials.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1095-1110"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289780","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}

{"title":"Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study.","authors":"Paulina B Lukow, Millie Lowther, Alexandra C Pike, Yumeya Yamamori, Alice V Chavanne, Siobhan Gormley, Jessica Aylward, Tayla McCloud, Talya Goble, Julia Rodriguez-Sanchez, Ella W Tuominen, Sarah K Buehler, Peter Kirk, Oliver J Robinson","doi":"10.1177/02698811241286773","DOIUrl":"10.1177/02698811241286773","url":null,"abstract":"<p><strong>Background: </strong>Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood.</p><p><strong>Aims: </strong>To investigate the neural correlates of subchronic antidepressant administration.</p><p><strong>Methods: </strong>We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (<i>n</i> = 96) and after subchronic escitalopram (<i>n</i> = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (<i>n</i> = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration.</p><p><strong>Results: </strong>Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration.</p><p><strong>Conclusions: </strong>To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may <i>increase</i> amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1071-1082"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372115","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}

{"title":"Towards precision dosing in psychiatry: Population pharmacokinetics meta-modelling of clozapine and lithium.","authors":"Aurélie Lereclus, Julien Welzel, Raoul Belzeaux, Théo Korchia, Frédéric Dayan, Olivier Blin, Sylvain Benito, Romain Guilhaumou","doi":"10.1177/02698811241275630","DOIUrl":"10.1177/02698811241275630","url":null,"abstract":"<p><strong>Background: </strong>Treatment optimization is mandatory in psychiatric diseases and the use of population pharmacokinetics (popPK) models through model informed precision dosing (MIPD) has the potential to improve patient medical care. In this perspective, meta-modelling methods could provide popPK models with improved predictive performances and most of covariates of interest. The aims of this study were to develop meta-models of clozapine and lithium, assess their predictability and propose optimized dosing regimens for both drugs.</p><p><strong>Methods: </strong>Two popPK models for each drug were retained to develop the meta-models. For clozapine, the model with the best predictive performances and gender as a covariate and one with smoking status were retained. For lithium, the model with the best predictive performances and fat-free mass as covariate and one with glomerular filtration rate were retained.</p><p><strong>Results: </strong>Both meta-models showed improved predictability compared to the original models. Clozapine meta-model simulations allowed us to propose dosing regimen according to gender and smoking status. Steady-state doses ranged from 375 to 725 mg/day for clozapine once daily, and from 350 to 650 mg/day for clozapine twice daily. Lithium meta-model simulations allowed us to propose dosing regimen according to weight, body mass index, gender and GFR. Our steady-state dose propositions ranged from 625 to 1125 mg/day for males, and from 375 to 750 mg/day for females.</p><p><strong>Conclusion: </strong>Both meta-models met the acceptability criteria for use in clinical practice on all subpopulations of interest. Those models could be used in the perspective of MIPD for clozapine and lithium.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1054-1062"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348924","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":"Optimizing the individual dosing of paroxetine in major depressive disorder with therapeutic drug monitoring.","authors":"Lingjun Zhong, Linlin Hu, Yinghui Li, Tianyu Wang, Suzhen Chen, Yuanyue Gao, Yonggui Yuan, Hua Shao","doi":"10.1177/02698811241278779","DOIUrl":"10.1177/02698811241278779","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies have examined the correlation between paroxetine concentrations and therapeutic efficacy in patients diagnosed with major depressive disorder (MDD), but findings have been contradictory.</p><p><strong>Aims: </strong>This study aimed to investigate the relationships among plasma concentrations, severity of symptoms, and adverse drug reactions (ADRs) to optimize individual dosing.</p><p><strong>Methods: </strong>Eighty-seven MDD patients, after completing treatment with paroxetine, were divided into low-concentration (LC, <i>n</i> = 38), medium-concentration (MC, <i>n</i> = 27), and high-concentration (HC, <i>n</i> = 22) groups, based on cutoff value concentrations with the 50% response rate and the laboratory alert level from the 2017 consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. The severity of depression and anxiety was evaluated using a 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA), respectively. Dosage, plasma concentrations, scale scores, and ADRs were recorded across the three groups at different treatment stages to define the therapeutic reference range.</p><p><strong>Results: </strong>The 4-week plasma concentration of paroxetine (65.00 ng/mL) could predict the clinical response in MDD patients at 8 weeks. Symptom relief in patients with 4-week paroxetine concentrations ranging from 65.00 to 120.00 ng/mL at 8 weeks was greater than in those with concentrations below 65.00 ng/mL, with no significant difference observed above this range. In addition, more cases of liver injury and weight gain were observed in patients with high paroxetine concentrations.</p><p><strong>Conclusion: </strong>Our results support that early paroxetine concentration may predict clinical efficacy and the incidence of ADRs, thus improving individual dosing regimens for MDD patients.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1063-1070"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348922","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":"Unidentified <i>CYP2D6</i> genotype does not affect pharmacological treatment for patients with first episode psychosis.","authors":"Emma Y De Brabander, Thérèse van Amelsvoort, Roos van Westrhenen","doi":"10.1177/02698811241279022","DOIUrl":"10.1177/02698811241279022","url":null,"abstract":"<p><strong>Background: </strong>Research on the pharmacogenetic influence of hepatic <i>CYP450</i> enzyme 2D6 (<i>CYP2D6</i>) on metabolism of drugs for psychosis and associated outcome has been inconclusive. Some results suggest increased risk of adverse reactions in poor and intermediate metabolizers, while others find no relationship. However, retrospective designs may fail to account for the long-term pharmacological treatment of patients. Previous studies found that clinicians adapted risperidone dose successfully without knowledge of patient <i>CYP2D6</i> phenotype.</p><p><strong>Aim: </strong>Here, we aimed to replicate the results of those studies in a Dutch cohort of patients with psychosis (<i>N</i> = 418) on pharmacological treatment.</p><p><strong>Method: </strong>We compared chlorpromazine-equivalent dose between <i>CYP2D6</i> metabolizer phenotypes and investigated which factors were associated with dosage. This was repeated in two smaller subsets; patients prescribed pharmacogenetics-actionable drugs according to published guidelines, and risperidone-only as done previously.</p><p><strong>Results: </strong>We found no relationship between chlorpromazine-equivalent dose and phenotype in any sample (complete sample: <i>p</i> = 0.3, actionable-subset: <i>p</i> = 0.82, risperidone-only: <i>p</i> = 0.34). Only clozapine dose was weakly associated with <i>CYP2D6</i> phenotype (<i>p</i> = 0.03).</p><p><strong>Conclusion: </strong>Clinicians were thus not intuitively adapting dose to <i>CYP2D6</i> activity in this sample, nor was <i>CYP2D6</i> activity associated with prescribed dose. Although the previous studies could not be replicated, this study may provide support for existing and future pharmacogenetic research.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1111-1121"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348925","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}

{"title":"Influence of panic disorder and paroxetine on brain functional hubs in drug-free patients.","authors":"Yingying Zhang, Haohao Yan, Yiding Han, Xiaoxiao Shan, Huabing Li, Feng Liu, Ping Li, Jingping Zhao, Wenbin Guo","doi":"10.1177/02698811241278780","DOIUrl":"10.1177/02698811241278780","url":null,"abstract":"<p><strong>Background: </strong>The effects of panic disorder (PD) and pharmacotherapy on brain functional hubs in drug-free patients, and the utility of their degree centrality (DC) in diagnosing and predicting treatment response (TR) for PD, remained unclear.</p><p><strong>Aims: </strong>This study aimed to assess the effects of PD and paroxetine on brain functional hubs in drug-free patients and to identify neuroimaging biomarkers for diagnosing and predicting TR in patients with PD.</p><p><strong>Methods: </strong>Imaging data from 54 medication-free PD patients and 54 matched healthy controls (HCs) underwent DC and functional connectivity (FC) analyses before and after a 4-week paroxetine treatment. Diagnosis and prediction of TR models for PD were constructed using support vector machine (SVM) and support vector regression (SVR), with DC as features.</p><p><strong>Results: </strong>Patients with PD showed aberrant DC and FC in the anterior cingulum, temporal, and occipital areas compared with HCs at baseline. After treatment, DC of the patients increased in the calcarine cortex, lingual gyrus, and cerebellum IV/V, along with improved clinical symptoms. Utilizing voxel-wise DC values at baseline, the SVM effectively distinguished patients with PD from HCs with an accuracy of 83.33%. In SVR, the predicted TR significantly correlated with the observed TR (correlation coefficient (<i>r</i>) = 0.893, Mean Squared Error = 0.009).</p><p><strong>Conclusion: </strong>Patients with PD exhibited abnormal DC and FC, notably in the limbic network, temporal, and occipital regions. Paroxetine ameliorated patients' symptoms while altering their brain FC. SVM and SVR models, utilizing baseline DC, effectively distinguished the patients from HCs and accurately predicted TR.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1083-1094"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289781","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}