{"title":"News on the Role of Antidepressants in and for COVID-19 and Long COVID.","authors":"Udo Bonnet, Georg Juckel","doi":"10.1055/a-2381-2117","DOIUrl":"https://doi.org/10.1055/a-2381-2117","url":null,"abstract":"","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351508","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}
Oscar Alcoverro-Fortuny, Ferran Viñas Usan, Carmen E Sanabria, Mikel Esnaola, José E Rojo Rodes
Objectives: The determination of anesthetic depth has been used to assess the optimal moment for applying electrical stimuli in electroconvulsive therapy (ECT), as some of the anesthetics used can reduce its effectiveness. In this study, seizure quality was assessed using anesthetic depth measurement with the patient state index (PSI).
Methods: A prospective experimental study was conducted with a control group, including a sample of 346 stimulations (PSI=134; Control=212) in 51 patients admitted and diagnosed with major depressive disorders. Seizure adequacy variables (seizure time in electroencephalogram [EEG] and motor activity, visual evaluation of the EEG, ECT-EEG parameter rating scale [EEPRS], seizure concordance, central inhibition, automated parameters, and autonomic activation) were assessed using linear mixed-effects models for continuous variables and generalized linear mixed-effects models for dichotomous variables.
Results: The PSI group required lower stimulation energy. The use of the PSI was associated with longer seizure time, both motor and electroencephalographic, higher quality of the EEG recording, better seizure concordance, and higher values for the automated parameters of maximum sustained coherence and time to peak coherence.
Conclusions: The use of the PSI to measure anesthetic depth may reduce the electrical stimulus charge required and improve seizure quality in ECT modified with propofol.
{"title":"Monitoring Anesthetic Depth Using the Patient State Index in Electroconvulsive Therapy Improves Seizure Quality.","authors":"Oscar Alcoverro-Fortuny, Ferran Viñas Usan, Carmen E Sanabria, Mikel Esnaola, José E Rojo Rodes","doi":"10.1055/a-2398-7693","DOIUrl":"https://doi.org/10.1055/a-2398-7693","url":null,"abstract":"<p><strong>Objectives: </strong>The determination of anesthetic depth has been used to assess the optimal moment for applying electrical stimuli in electroconvulsive therapy (ECT), as some of the anesthetics used can reduce its effectiveness. In this study, seizure quality was assessed using anesthetic depth measurement with the patient state index (PSI).</p><p><strong>Methods: </strong>A prospective experimental study was conducted with a control group, including a sample of 346 stimulations (PSI=134; Control=212) in 51 patients admitted and diagnosed with major depressive disorders. Seizure adequacy variables (seizure time in electroencephalogram [EEG] and motor activity, visual evaluation of the EEG, ECT-EEG parameter rating scale [EEPRS], seizure concordance, central inhibition, automated parameters, and autonomic activation) were assessed using linear mixed-effects models for continuous variables and generalized linear mixed-effects models for dichotomous variables.</p><p><strong>Results: </strong>The PSI group required lower stimulation energy. The use of the PSI was associated with longer seizure time, both motor and electroencephalographic, higher quality of the EEG recording, better seizure concordance, and higher values for the automated parameters of maximum sustained coherence and time to peak coherence.</p><p><strong>Conclusions: </strong>The use of the PSI to measure anesthetic depth may reduce the electrical stimulus charge required and improve seizure quality in ECT modified with propofol.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308288","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}
Manouk den Toom, Laura Blanken, Inge Horn, Selene Veerman, Joris J B van der Vlugt-Molenaar, Mariken B de Koning, Jan Bogers, John Enterman, Martin de Jonge, Daniela Cianci, Gerardus W J Frederix, Hans J de Haas, Bram W Storosum, Mike Veereschild, Martin Javadzadeh, Peter F J Schulte, Dan Cohen, Jim van Os, Wiepke Cahn, Lieuwe de Haan, Jasper B Zantvoord, Jurjen J Luykx
{"title":"Correction: Electroconvulsive Therapy Versus Aripiprazole Addition to Clozapine in Patients with Clozapine-Resistant Symptoms (EMECLO): A Protocol of a Single-Blind, Multicenter, Randomized-Controlled Feasibility Trial.","authors":"Manouk den Toom, Laura Blanken, Inge Horn, Selene Veerman, Joris J B van der Vlugt-Molenaar, Mariken B de Koning, Jan Bogers, John Enterman, Martin de Jonge, Daniela Cianci, Gerardus W J Frederix, Hans J de Haas, Bram W Storosum, Mike Veereschild, Martin Javadzadeh, Peter F J Schulte, Dan Cohen, Jim van Os, Wiepke Cahn, Lieuwe de Haan, Jasper B Zantvoord, Jurjen J Luykx","doi":"10.1055/a-2406-6396","DOIUrl":"https://doi.org/10.1055/a-2406-6396","url":null,"abstract":"","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146025","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}
Pub Date : 2024-09-01Epub Date: 2024-07-31DOI: 10.1055/a-2334-6253
Garrett D Alexander, Luke R Cavanah, Jessica L Goldhirsh, Leighton Y Huey, Brian J Piper
Introduction: There have been substantial increases in the use of Schedule II stimulants in the United States. Schedule II stimulants are the gold standard treatment for attention-deficit hyperactivity disorder (ADHD), but also carry the risk of addiction. Since the neurocognitive deficits seen in ADHD resemble those of chronic cannabis use, and the rise in stimulant use is incompletely understood, this study sought to determine if recreational cannabis (RC) legalization increased distribution rates of Schedule II stimulants.
Methods: The distribution of amphetamine, lisdexamfetamine, and methylphenidate were extracted from the ARCOS database of the Drug Enforcement Administration. The three-year population-corrected slopes of distribution before and after RC sales were evaluated.
Results: Total stimulant distribution rates were significantly higher in states with RC sales after (p=0.049), but not before (p=0.221), program implementation compared to states without RC. Significant effects of time (p<0.001) and RC sales status (p=0.045) were observed, while time x RC sales status interaction effects were not significant (p=0.406).
Discussion: RC legalization did not contribute to a more pronounced rise in Schedule II stimulant distribution in states. Future studies could explore the impact of illicit cannabis use on stimulant rates and the impact of cannabis sales on distribution rates of non-stimulant ADHD pharmacotherapies and ADHD diagnoses.
导言:在美国,二类兴奋剂的使用大幅增加。第二类兴奋剂是治疗注意力缺陷多动障碍(ADHD)的金标准,但也有成瘾的风险。由于注意力缺陷多动障碍(ADHD)的神经认知缺陷与长期吸食大麻相似,而且人们对兴奋剂使用的增加还不完全了解,因此本研究试图确定娱乐性大麻(RC)合法化是否会增加附表 II 兴奋剂的销售率:从缉毒署的 ARCOS 数据库中提取了苯丙胺、利眠宁和哌醋甲酯的分布情况。对 RC 销售前后三年的人口校正分布斜率进行了评估:与未实施 RC 的州相比,在实施 RC 计划后(p=0.049),而在实施 RC 计划前(p=0.221),有 RC 销售的州的兴奋剂总销售率明显较高。观察到时间的显著影响(pp=0.045),而时间 x RC 销售状况的交互影响不显著(p=0.406):讨论:RC 合法化并未导致各州附表 II 兴奋剂销售量的明显上升。今后的研究可以探讨非法使用大麻对兴奋剂使用率的影响,以及大麻销售对非兴奋剂多动症药物疗法和多动症诊断分布率的影响。
{"title":"Recreational Cannabis Legalization: No Contribution to Rising Prescription Stimulants in the USA.","authors":"Garrett D Alexander, Luke R Cavanah, Jessica L Goldhirsh, Leighton Y Huey, Brian J Piper","doi":"10.1055/a-2334-6253","DOIUrl":"10.1055/a-2334-6253","url":null,"abstract":"<p><strong>Introduction: </strong>There have been substantial increases in the use of Schedule II stimulants in the United States. Schedule II stimulants are the gold standard treatment for attention-deficit hyperactivity disorder (ADHD), but also carry the risk of addiction. Since the neurocognitive deficits seen in ADHD resemble those of chronic cannabis use, and the rise in stimulant use is incompletely understood, this study sought to determine if recreational cannabis (RC) legalization increased distribution rates of Schedule II stimulants.</p><p><strong>Methods: </strong>The distribution of amphetamine, lisdexamfetamine, and methylphenidate were extracted from the ARCOS database of the Drug Enforcement Administration. The three-year population-corrected slopes of distribution before and after RC sales were evaluated.</p><p><strong>Results: </strong>Total stimulant distribution rates were significantly higher in states with RC sales after (<i>p</i>=0.049), but not before (<i>p</i>=0.221), program implementation compared to states without RC. Significant effects of time (<i>p</i><0.001) and RC sales status (<i>p</i>=0.045) were observed, while time x RC sales status interaction effects were not significant (<i>p</i>=0.406).</p><p><strong>Discussion: </strong>RC legalization did not contribute to a more pronounced rise in Schedule II stimulant distribution in states. Future studies could explore the impact of illicit cannabis use on stimulant rates and the impact of cannabis sales on distribution rates of non-stimulant ADHD pharmacotherapies and ADHD diagnoses.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860524","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}
Pub Date : 2024-09-01Epub Date: 2024-08-01DOI: 10.1055/a-2345-7448
Simon Kurzhals, Martin Schäfer, Udo Bonnet, Katrin Isbruch, Stefan Kühnhold, Jörg Timm, Michael Specka, Norbert Scherbaum
Introduction: People addicted to illegal drugs were discussed as a risk group for SARS-CoV-2 infections, with increased susceptibility and a severe course of infection.
Methods: In this study, the frequency of SARS-CoV-2 infections of drug-dependent persons admitted to inpatient detoxification treatment in five psychiatric hospitals was determined by implementing routine polymerase chain reaction (PCR)-testing at admission (9/2020) up to one year. Main substance-related diagnosis, comorbid respiratory disease, housing situation, and current opioid maintenance treatment (OMT) were documented. An age-matched control group of psychiatric inpatients without dependence from illegal drugs was established.
Results: Data from 1675 patients (male 79.5%; mean age 39.5 years; opioid dependence 81.5% homelessness; 2.4%; chronic respiratory disease 6.3%) were included. Out of 1365 patients dependent on opioids, 50.2% were currently in OMT. Six (3 female; mean age 40.3 years) patients tested positive for SARS-CoV-2 by PCR (0.36%), and none showed symptoms of COVID-19. All six were opioid dependent, 5 currently not in OMT. In the control group, 11 out of 1811 inpatients tested positive (0.61%).
Discussion: The rate of SARS-CoV-2-infections in persons with dependence on illegal drugs was not increased compared to a control group of psychiatric patients. OMT is presumably a protective factor, e. g. in the participating cities, OMT facilities offered an easy access to vaccination programs. In contrast, drug addicts in the USA were severely affected by the pandemic. Differences between countries might partially be explained by social factors such as the higher availability of OMT in Germany and a much lower frequency of homelessness.
{"title":"SARS-CoV-2-Infection in People Addicted to Illegal Drugs - Is There a Protective Effect of Opioid Maintenance Treatment?","authors":"Simon Kurzhals, Martin Schäfer, Udo Bonnet, Katrin Isbruch, Stefan Kühnhold, Jörg Timm, Michael Specka, Norbert Scherbaum","doi":"10.1055/a-2345-7448","DOIUrl":"10.1055/a-2345-7448","url":null,"abstract":"<p><strong>Introduction: </strong>People addicted to illegal drugs were discussed as a risk group for SARS-CoV-2 infections, with increased susceptibility and a severe course of infection.</p><p><strong>Methods: </strong>In this study, the frequency of SARS-CoV-2 infections of drug-dependent persons admitted to inpatient detoxification treatment in five psychiatric hospitals was determined by implementing routine polymerase chain reaction (PCR)-testing at admission (9/2020) up to one year. Main substance-related diagnosis, comorbid respiratory disease, housing situation, and current opioid maintenance treatment (OMT) were documented. An age-matched control group of psychiatric inpatients without dependence from illegal drugs was established.</p><p><strong>Results: </strong>Data from 1675 patients (male 79.5%; mean age 39.5 years; opioid dependence 81.5% homelessness; 2.4%; chronic respiratory disease 6.3%) were included. Out of 1365 patients dependent on opioids, 50.2% were currently in OMT. Six (3 female; mean age 40.3 years) patients tested positive for SARS-CoV-2 by PCR (0.36%), and none showed symptoms of COVID-19. All six were opioid dependent, 5 currently not in OMT. In the control group, 11 out of 1811 inpatients tested positive (0.61%).</p><p><strong>Discussion: </strong>The rate of SARS-CoV-2-infections in persons with dependence on illegal drugs was not increased compared to a control group of psychiatric patients. OMT is presumably a protective factor, e. g. in the participating cities, OMT facilities offered an easy access to vaccination programs. In contrast, drug addicts in the USA were severely affected by the pandemic. Differences between countries might partially be explained by social factors such as the higher availability of OMT in Germany and a much lower frequency of homelessness.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875585","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}
Pub Date : 2024-09-01Epub Date: 2024-06-19DOI: 10.1055/a-2331-2300
Taro Kishi, Kenji Sakuma, Shun Hamanaka, Yasufumi Nishii, Nakao Iwata
Introduction: Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317).
Methods: This is a retrospective cohort study.
Results: Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively.
Discussion: The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.
{"title":"Discontinuation Rate of Lurasidone and Quetiapine Extended Release in Bipolar Depression.","authors":"Taro Kishi, Kenji Sakuma, Shun Hamanaka, Yasufumi Nishii, Nakao Iwata","doi":"10.1055/a-2331-2300","DOIUrl":"10.1055/a-2331-2300","url":null,"abstract":"<p><strong>Introduction: </strong>Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317).</p><p><strong>Methods: </strong>This is a retrospective cohort study.</p><p><strong>Results: </strong>Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively.</p><p><strong>Discussion: </strong>The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427309","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}
Introduction: Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.
Methods: A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.
Results: Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.
Discussion: Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.
导言:传统的抗精神病药物可减轻多巴胺能神经传递,但对大约三分之一的精神分裂症患者无效。因此有必要开发非多巴胺能药物:方法:利用美国临床试验注册中心和欧盟临床试验注册中心,对已完成的精神分裂症治疗化合物 II 期和 III 期试验进行了系统检索。在最新的II期和III期试验中,在主要结果指标上明显优于安慰剂的化合物被确定下来。通过人工搜索PubMed和新闻稿,收集了所纳入化合物的相关信息:结果:共确定了16种化合物,其中4种化合物(乌洛他隆、沙诺美林/氯化曲塞膦、伐比卡西林和罗鲁哌酮)作为单一疗法进行了研究,其余12种化合物(匹马万塞林、比托哌汀、BI 425809、安塞尼可林、托吡司琼、孕烯醇酮、D-丝氨酸、雌二醇、托卡朋、伐昔洛韦、大麻二酚和利莫那班)作为附加疗法进行了研究。与安慰剂相比,乌洛他隆、沙诺美林/氯化曲安奈德、伐比卡西林、比托泊汀、雌二醇、大麻二酚、利莫那班和D-丝氨酸对阳性症状有疗效;罗哌利酮和匹马万赛林对阴性症状有效;安可奈林、托吡司琼、孕烯诺龙、托卡朋、BI 425809和伐昔洛韦改善了认知功能:讨论:功能不同于现有抗精神病药物的化合物可为精神分裂症患者提供新的症状特异性治疗策略。
{"title":"Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments.","authors":"Yuki Komatsu, Moe Takehara, Xenia Hart, Yuna Takahashi, Satoko Hori, Fumihiko Ueno, Hiroyuki Uchida","doi":"10.1055/a-2307-6484","DOIUrl":"10.1055/a-2307-6484","url":null,"abstract":"<p><strong>Introduction: </strong>Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.</p><p><strong>Methods: </strong>A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.</p><p><strong>Results: </strong>Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.</p><p><strong>Discussion: </strong>Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860277","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}
Pub Date : 2024-09-01Epub Date: 2024-06-25DOI: 10.1055/a-2313-9979
Farhana Islam, Amanda Lisoway, Edward S Oh, Laura M Fiori, Leen Magarbeh, Samar S M Elsheikh, Helena K Kim, Stefan Kloiber, James L Kennedy, Benicio N Frey, Roumen Milev, Claudio N Soares, Sagar V Parikh, Franca Placenza, Stefanie Hassel, Valerie H Taylor, Francesco Leri, Pierre Blier, Rudolf Uher, Faranak Farzan, Raymond W Lam, Gustavo Turecki, Jane A Foster, Susan Rotzinger, Sidney H Kennedy, Daniel J Müller
Introduction: Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19, CYP2D6, CYP3A4, and ABCB1, and its effect on these outcomes.
Methods: The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects.
Results: Eleven cis-SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain (q=0.027) and serum concentrations of ESCadj (q<0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESCadj concentrations. CITs did not indicate that these effects were epigenetically mediated.
Discussion: These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored.
{"title":"Integrative Genetic Variation, DNA Methylation, and Gene Expression Analysis of Escitalopram and Aripiprazole Treatment Outcomes in Depression: A CAN-BIND-1 Study.","authors":"Farhana Islam, Amanda Lisoway, Edward S Oh, Laura M Fiori, Leen Magarbeh, Samar S M Elsheikh, Helena K Kim, Stefan Kloiber, James L Kennedy, Benicio N Frey, Roumen Milev, Claudio N Soares, Sagar V Parikh, Franca Placenza, Stefanie Hassel, Valerie H Taylor, Francesco Leri, Pierre Blier, Rudolf Uher, Faranak Farzan, Raymond W Lam, Gustavo Turecki, Jane A Foster, Susan Rotzinger, Sidney H Kennedy, Daniel J Müller","doi":"10.1055/a-2313-9979","DOIUrl":"10.1055/a-2313-9979","url":null,"abstract":"<p><strong>Introduction: </strong>Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, <i>CYP2C19</i>, <i>CYP2D6</i>, <i>CYP3A4</i>, and <i>ABCB1</i>, and its effect on these outcomes.</p><p><strong>Methods: </strong>The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects.</p><p><strong>Results: </strong>Eleven <i>cis-</i>SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, <i>CYP2C19</i> rs4244285 was associated with treatment-related weight gain (<i>q</i>=0.027) and serum concentrations of ESC<sub>adj</sub> (<i>q</i><0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESC<sub>adj</sub> concentrations. CITs did not indicate that these effects were epigenetically mediated.</p><p><strong>Discussion: </strong>These results elucidate functional mechanisms underlying the established associations between <i>CYP2C19</i> rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451121","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}
Objective: To determine if the cardiac function and "endocrinium" of Chinese patients are associated with dopamine D2 (DRD2) (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms when treated with amisulpride.
Methods: This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic discrimination.
Results: Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the rs6276 AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E2) level in rs6276 GG and rs963468 GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in rs6276 GG and rs963468 GG groups was the highest among their different genotype groups. The increase in the level of "AST" in the rs6280 TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of "CK" in the rs6280 CT group was higher than that in the CC and CT groups. Besides, the increased level of "PRL" in the rs6280 CC group and rs963468 GG group was higher than that in their other two genotypes groups.
Conclusion: DRD2 (rs6276) and DRD3 (rs6280, rs963468) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia.
目的确定中国患者在接受氨磺必利治疗时,其心脏功能和 "内分泌 "是否与多巴胺D2(DRD2)(rs6276)和DRD3(rs6280,rs963468)基因多态性有关:本研究招募了 148 名精神分裂症患者,这些患者口服阿米舒必利 8 周。采用TaqMan-MGB等位基因辨别法检测DRD2(rs6276)和DRD3(rs6280、rs963468)基因多态性:多变量协方差分析(MANCOVA)显示,在调整年龄、性别和基线水平后,rs6276 AG 组天门冬氨酸氨基转移酶(AST)和肌酸激酶(CK)水平的升高幅度高于 AA 组和 GG 组。同样,rs6276 GG 组和 rs963468 GG 组的雌二醇(E2)水平变化也高于其他两组。调整协变量后,rs6276 GG 组和 rs963468 GG 组甘油三酯(TG)水平的升高在不同基因型组中最高。在调整协变量后,rs6280 TT 组 "谷草转氨酶 "水平的升高幅度高于 CC 组和 CT 组。同样,MANCOVA 显示,rs6280 CT 组 "肌酸激酶 "水平的升高也高于 CC 组和 CT 组。此外,rs6280 CC 组和 rs963468 GG 组 "PRL "水平的升高也高于其他两个基因型组:结论:DRD2(rs6276)和DRD3(rs6280、rs963468)多态性可能影响阿米舒必利的耐受性,因为它们与观察到的不良反应有关,包括中国精神分裂症患者的心功能障碍和内分泌紊乱。
{"title":"Association Study Between DRD2, DRD3 Genetic Polymorphisms and Adverse Reactions in Chinese Patients on Amisulpride Treatment.","authors":"Kankan Qu, Yanan He, Zhongdong Zhang, Yeli Cao, Qiyun Qin, Zhenhe Zhou, Lili Zhen","doi":"10.1055/a-2375-3859","DOIUrl":"https://doi.org/10.1055/a-2375-3859","url":null,"abstract":"<p><strong>Objective: </strong>To determine if the cardiac function and \"endocrinium\" of Chinese patients are associated with dopamine D<sub>2</sub> (<i>DRD2</i>) (<i>rs6276</i>) and <i>DRD3</i> (<i>rs6280, rs963468</i>) genetic polymorphisms when treated with amisulpride.</p><p><strong>Methods: </strong>This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. <i>DRD2 (rs6276)</i> and <i>DRD3 (rs6280, rs963468)</i> genetic polymorphisms were detected with TaqMan-MGB allelic discrimination.</p><p><strong>Results: </strong>Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the <i>rs6276</i> AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E<sub>2</sub>) level in <i>rs6276</i> GG and <i>rs963468</i> GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in <i>rs6276</i> GG and <i>rs963468</i> GG groups was the highest among their different genotype groups. The increase in the level of \"AST\" in the <i>rs6280</i> TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of \"CK\" in the <i>rs6280</i> CT group was higher than that in the CC and CT groups. Besides, the increased level of \"PRL\" in the <i>rs6280</i> CC group and <i>rs963468</i> GG group was higher than that in their other two genotypes groups.</p><p><strong>Conclusion: </strong><i>DRD2</i> (<i>rs6276</i>) and <i>DRD3</i> (<i>rs6280, rs963468</i>) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073461","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}
Manouk den Toom, Laura Blanken, Inge Horn, Selene Veerman, Joris J B van der Vlugt-Molenaar, Mariken B de Koning, Jan Bogers, John Enterman, Martin de Jonge, Daniela Cianci, Gerardus W J Frederix, Hans J de Haas, Bram W Storosum, Mike Veereschild, Martin Javadzadeh, Peter F J Schulte, Dan Cohen, Jim van Os, Wiepke Cahn, Lieuwe de Haan, Jasper B Zantvoord, Jurjen J Luykx
Background: Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS.
Methods: In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment.
Discussion: Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT.
Trial registration: The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021-006333-19).
{"title":"Electroconvulsive Therapy Versus Aripiprazole Addition to Clozapine in Patients with Clozapine-Resistant Symptoms (EMECLO): A Protocol of a Single-Blind, Multicenter, Randomized-Controlled Feasibility Trial.","authors":"Manouk den Toom, Laura Blanken, Inge Horn, Selene Veerman, Joris J B van der Vlugt-Molenaar, Mariken B de Koning, Jan Bogers, John Enterman, Martin de Jonge, Daniela Cianci, Gerardus W J Frederix, Hans J de Haas, Bram W Storosum, Mike Veereschild, Martin Javadzadeh, Peter F J Schulte, Dan Cohen, Jim van Os, Wiepke Cahn, Lieuwe de Haan, Jasper B Zantvoord, Jurjen J Luykx","doi":"10.1055/a-2364-4357","DOIUrl":"10.1055/a-2364-4357","url":null,"abstract":"<p><strong>Background: </strong>Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS.</p><p><strong>Methods: </strong>In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment.</p><p><strong>Discussion: </strong>Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT.</p><p><strong>Trial registration: </strong>The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021-006333-19).</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073462","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}