Human Psychopharmacology: Clinical and Experimental最新文献_第10页

N,N-dimethyltryptamine and Amazonian ayahuasca plant medicine N、 N-二甲基色胺和亚马逊阿亚瓦斯卡植物药。

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2022-02-17 DOI: 10.1002/hup.2835

Edward James, Joachim Keppler, Thomas L Robertshaw, Ben Sessa

Objective

Reports have indicated possible uses of ayahuasca for the treatment of conditions including depression, addictions, post-traumatic stress disorder, anxiety and specific psychoneuroendocrine immune system pathologies. The article assesses potential ayahuasca and N,N-dimethyltryptamine (DMT) integration with contemporary healthcare. The review also seeks to provide a summary of selected literature regarding the mechanisms of action of DMT and ayahuasca; and assess to what extent the state of research can explain reports of unusual phenomenology.

Design

A narrative review.

Results

Compounds in ayahuasca have been found to bind to serotonergic receptors, glutaminergic receptors, sigma-1 receptors, trace amine-associated receptors, and modulate BDNF expression and the dopaminergic system. Subjective effects are associated with increased delta and theta oscillations in amygdala and hippocampal regions, decreased alpha wave activity in the default mode network, and stimulations of vision-related brain regions particularly in the visual association cortex. Both biological processes and field of consciousness models have been proposed to explain subjective effects of DMT and ayahuasca, however, the evidence supporting the proposed models is not sufficient to make confident conclusions. Ayahuasca plant medicine and DMT represent potentially novel treatment modalities.

Conclusions

Further research is required to clarify the mechanisms of action and develop treatments which can be made available to the general public. Integration between healthcare research institutions and reputable practitioners in the Amazon is recommended.

目的：报告表明阿亚瓦斯卡可能用于治疗抑郁症、成瘾、创伤后应激障碍、焦虑症和特定的心理神经内分泌免疫系统疾病。本文评估了阿亚瓦斯卡和N，N-二甲基色胺（DMT）与当代医疗保健的潜在整合。该综述还试图提供有关DMT和阿亚瓦斯卡作用机制的精选文献摘要；并评估研究状态在多大程度上可以解释异常现象学的报道。设计：叙述性回顾。结果：阿亚瓦斯卡中的化合物已被发现与5-羟色胺能受体、谷氨酰胺能受体、sigma-1受体、微量胺相关受体结合，并调节BDNF的表达和多巴胺能系统。主观效应与杏仁核和海马区域的δ和θ振荡增加、默认模式网络中的α波活动减少以及视觉相关大脑区域的刺激有关，尤其是视觉联想皮层。生物过程和意识场模型都被提出来解释DMT和阿亚瓦斯卡的主观影响，然而，支持所提出的模型的证据不足以得出可信的结论。Ayawasca植物药和DMT代表了潜在的新型治疗模式。结论：需要进一步的研究来阐明作用机制，并开发可向公众提供的治疗方法。建议将医疗保健研究机构和亚马逊知名从业者整合在一起。

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引用次数: 13

Effects of ayahuasca on the endocannabinoid system of healthy volunteers and in volunteers with social anxiety disorder: Results from two pilot, proof-of-concept, randomized, placebo-controlled trials 死藤水对健康志愿者和社交焦虑症志愿者内源性大麻素系统的影响:来自两个试点、概念验证、随机、安慰剂对照试验的结果

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2022-02-02 DOI: 10.1002/hup.2834

Rafael G. dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi, Flávia L. Osório, Genís Ona, José Carlos Bouso, Gabriela de Oliveira Silveira, Mauricio Yonamine, Camila Marchioni, Eduardo José Crevelin, Maria Eugênia Queiroz, José Alexandre Crippa, Jaime E. C. Hallak

Objective

To assess endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo.

Methods

Post hoc analysis of endocannabinoid plasma levels (baseline, 90 and 240 min after drug intake) from two parallel-group, randomized, placebo-controlled trials. In Study 1, 20 healthy volunteers ingested ayahuasca (average 1.58 mg/ml dimethyltryptamine (DMT)) or placebo, and in Study 2, 17 volunteers with SAD received ayahuasca (average 0.680 mg/ml DMT) or placebo.

Results

A significant difference was observed in AEA concentrations in Study 2 after ayahuasca intake (Χ²(2) = 6.5, p = 0.03, Friedman test), and near significant differences (increases) were observed between baseline and 90 (Z = 0, p = 0.06, Wilcoxon test) and 240 (Z = 10, p = 0.06) minutes after ayahuasca intake.

Conclusions

Although our findings suggest that ayahuasca could modulate AEA levels in SAD patients, the high interindividual variability in both trials and the small samples preclude definitive conclusions. More research with larger samples is needed to better understand the effects of ayahuasca and other hallucinogens in the endocannabinoid system.

目的评价内源性大麻素(anandamide, AEA);2-花生四烯醇甘油酯(2-AG)在健康志愿者和患有社交焦虑症(SAD)的志愿者口服单剂量死水或安慰剂后的血浆水平。方法对两个平行组、随机、安慰剂对照试验的内源性大麻素血浆水平(服药后基线、服药后90分钟和服药后240分钟)进行事后分析。在研究1中，20名健康志愿者服用死水(平均1.58 mg/ml二甲色胺(DMT))或安慰剂，在研究2中，17名患有SAD的志愿者服用死水(平均0.680 mg/ml DMT)或安慰剂。结果研究2中服用死藤水后AEA浓度差异有统计学意义(Χ2(2) = 6.5, p = 0.03, Friedman检验)，且与服用死藤水后90分钟(Z = 0, p = 0.06, Wilcoxon检验)和240分钟(Z = 10, p = 0.06)相比差异接近统计学意义(增加)。虽然我们的研究结果表明死藤水可以调节SAD患者的AEA水平，但两项试验的高个体间差异和小样本排除了明确的结论。为了更好地了解死藤水和其他致幻剂对内源性大麻素系统的影响，需要更多的研究和更大的样本。

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引用次数: 6

Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders 5 -羟色胺转运体基因多态性与新诊断重度抑郁症患者抗抑郁药物舍曲林、米氮平疗效的关系

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2022-01-28 DOI: 10.1002/hup.2833

Syed Gulfishan, Sumita Halder, Rajarshi Kar, Shruti Srivastava, Rachna Gupta

Objective

We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST).

Method

Newly diagnosed, treatment naïve, 80 MDD patients (aged 18–45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15–45 mg/day or ST 25–200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL.

Result

We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs.

Conclusion

Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.

目的探讨重度抑郁症患者血清素受体转运体基因多态性与米氮平(MZ)、舍曲林(ST)临床疗效的关系。方法采用DSM-5标准诊断，Beck抑郁量表评分(BDI)≥21分，新诊断、治疗naïve的MDD患者80例(18-45岁)，随机分为两组，每组40例，分别给予MZ 15 ~ 45mg /d或ST 25 ~ 200mg /d。随访6周，评估BDI评分。进行基因型评估，根据聚合酶链反应片段大小鉴定出三个等位基因变异:短(S;486 bp)，长(L;529bp)，或外沿(XL;基因型分别为S/S、S/L、L/L、S/XL和L/XL。结果32.5%的患者属于S/S基因型，提示SS基因型患者发生重度抑郁症的风险较高。在基因型的基础上，未发现与ST或MZ组有统计学意义的关联。两种药物治疗6周后，观察到临床显著改善，BDI评分降低50%以上。结论基因型检测可用于高危人群的识别。重度抑郁症患者先前的基因分型可能有助于预测使用抗抑郁药的更好临床结果。

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引用次数: 0

The chemical induction of synaesthesia 联觉的化学诱导

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2022-01-19 DOI: 10.1002/hup.2832

David P. Luke, Laura Lungu, Ross Friday, Devin B. Terhune

Objective

Preliminary research suggests that experiences resembling synaesthesia are frequently reported under the influence of a diverse range of chemical substances although the incidence, chemical specificity, and characteristics of these effects are poorly understood.

Methods

Here we surveyed recreational drug users and self-reported developmental synaesthetes regarding their use of 28 psychoactive drugs from 12 different drug classes and whether they had experienced synaesthesia under the influence of these substances.

Results

The drug class of tryptamines exhibited the highest incidence rates of drug-induced synaesthesia in controls and induction rates of novel forms of synaesthesia in developmental synaesthetes. Induction incidence rates in controls were strongly correlated with the corresponding induction and enhancement rates in developmental synaesthetes. In addition, the use of lysergic acid diethylamide (LSD) was the strongest predictor of drug-induced synaesthesia in both controls and developmental synaesthetes. Clear evidence was observed for a clustering of synaesthesia-induction rates as a function of drug class in both groups, denoting non-random incidence rates within drug classes. Sound-colour synaesthesia was the most commonly observed type of induced synaesthesia. Further analyses suggest the presence of synaesthesia-prone individuals, who were more likely to experience drug-induced synaesthesia with multiple drugs.

Conclusions

These data corroborate the hypothesized link between drug-induced synaesthesia and serotoninergic activity, but also suggest the possibility of alternative neurochemical pathways involved in the induction of synaesthesia. They further imply that the induction and modulation of synaesthesia in controls and developmental synaesthetes share overlapping mechanisms and that certain individuals may be more susceptible to experiencing induced synaesthesia with different drugs.

目的:初步研究表明，在多种化学物质的影响下，类似联觉的体验经常被报道，尽管这些影响的发生率、化学特异性和特征尚不清楚。方法调查了娱乐性药物使用者和自我报告的发展性联觉者对12种不同药物类别的28种精神活性药物的使用情况，以及他们是否在这些药物的影响下经历过联觉。结果色胺类药物在对照组中具有最高的药物性联觉发生率，在发展性联觉者中具有最高的新型联觉诱导率。对照组的诱导发生率与发育联觉者相应的诱导和增强率密切相关。此外，麦角酸二乙胺(LSD)的使用是对照组和发展性联觉者药物诱导联觉的最强预测因子。明确的证据表明，在两组中，联觉诱导率作为药物类别的函数呈聚类，表明药物类别内的非随机发生率。声音-颜色联觉是最常见的诱导联觉类型。进一步的分析表明，联觉倾向个体的存在，他们更有可能经历多种药物引起的联觉。结论这些数据证实了药物诱导的联觉与血清素能活性之间的联系，但也表明可能有其他神经化学途径参与联觉的诱导。他们进一步暗示，控制联觉和发育联觉的联觉的诱导和调节有重叠的机制，某些个体可能更容易经历不同药物诱导的联觉。

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引用次数: 4

Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder 5 -羟色胺转运体和受体基因多态性在选择性5 -羟色胺再摄取抑制剂治疗反应中的作用

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2022-01-06 DOI: 10.1002/hup.2830

Varsha Ramesh, Vettriselvi Venkatesan, Balakrishnan Ramasamy

Objective

Significant challenges in the management of major depressive disorder include the lag period from treatment initiation to an evident response, low response rates and unpredictable disparities in outcome between patients. As a large part of these has been linked to genetic mechanisms, we tried to establish a relationship between genes associated with serotonin neurotransmission and outcome to selective serotonin reuptake inhibitor (SSRI) treatment.

Methods

One hundred and twenty-five patients with moderate to severe depression [at least 15 on the Hamilton Depression (HAM-D) Rating Scale] being started on SSRI were recruited. Those with a reduction of at least 50% from baseline or an absolute score of 7 or less after 8 weeks of treatment were considered as responders. The serotonin transporter linked polymorphic region 5HTTLPR, serotonin transporter intron 2 (STin2) polymorphism and the 5-HT receptor 1A rs6295 polymorphisms were studied in association with outcome.

Results

The l/l genotype of the 5HTTLPR was associated with greater likelihood of response (OR: 4.65, CI: 1.74–12.38, p = 0.003). Patients with the 12/12 repeat variant of the STin2 VNTR polymorphism showed a greater reduction in HAM-D score, compared to patients with the 10/10 genotype (OR: 0.12, CI: 0.03–0.44, p = 0.001). We found no association of the 5HTR1Ars6295 polymorphism with response.

Conclusions

The 5HTTLPR polymorphism and the SLC6A4 intron 2 polymorphism were associated with treatment response, with the l/l genotype and 12-copy allele showing a tendency towards better outcomes, respectively.

目的重性抑郁症治疗面临的重大挑战包括从治疗开始到明显反应的滞后期、低反应率和患者之间不可预测的结果差异。由于其中很大一部分与遗传机制有关，我们试图建立与血清素神经传递相关的基因与选择性血清素再摄取抑制剂(SSRI)治疗结果之间的关系。方法选取125例开始接受SSRI治疗的中重度抑郁症患者(Hamilton depression (HAM-D) Rating Scale≥15例)。那些在治疗8周后从基线减少至少50%或绝对得分为7或更低的患者被认为是应答者。研究了5-羟色胺转运蛋白相关多态性区5HTTLPR、5-羟色胺转运蛋白内含子2 (STin2)多态性和5-羟色胺受体1A rs6295多态性与预后的关系。结果5HTTLPR的l/l基因型与更大的应答可能性相关(OR: 4.65, CI: 1.74 ~ 12.38, p = 0.003)。与10/10基因型患者相比，携带STin2 VNTR多态性12/12重复变体的患者在HAM-D评分上的下降幅度更大(OR: 0.12, CI: 0.03-0.44, p = 0.001)。我们发现5HTR1Ars6295多态性与应答没有关联。结论5HTTLPR多态性和SLC6A4内含子2多态性与治疗效果相关，1 /l基因型和12拷贝等位基因分别表现出较好的预后趋势。

{"title":"Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder","authors":"Varsha Ramesh, Vettriselvi Venkatesan, Balakrishnan Ramasamy","doi":"10.1002/hup.2830","DOIUrl":"10.1002/hup.2830","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Significant challenges in the management of major depressive disorder include the lag period from treatment initiation to an evident response, low response rates and unpredictable disparities in outcome between patients. As a large part of these has been linked to genetic mechanisms, we tried to establish a relationship between genes associated with serotonin neurotransmission and outcome to selective serotonin reuptake inhibitor (SSRI) treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One hundred and twenty-five patients with moderate to severe depression [at least 15 on the Hamilton Depression (HAM-D) Rating Scale] being started on SSRI were recruited. Those with a reduction of at least 50% from baseline or an absolute score of 7 or less after 8 weeks of treatment were considered as responders. The serotonin transporter linked polymorphic region 5HTTLPR, serotonin transporter intron 2 (STin2) polymorphism and the 5-HT receptor 1A rs6295 polymorphisms were studied in association with outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The l/l genotype of the 5HTTLPR was associated with greater likelihood of response (OR: 4.65, CI: 1.74–12.38, <i>p</i> = 0.003). Patients with the 12/12 repeat variant of the STin2 VNTR polymorphism showed a greater reduction in HAM-D score, compared to patients with the 10/10 genotype (OR: 0.12, CI: 0.03–0.44, <i>p</i> = 0.001). We found no association of the 5HTR1Ars6295 polymorphism with response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The 5HTTLPR polymorphism and the SLC6A4 intron 2 polymorphism were associated with treatment response, with the l/l genotype and 12-copy allele showing a tendency towards better outcomes, respectively.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"37 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39905868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Psychopharmacoepidemiology of antidepressant medications among homeless and unstably housed service users in the Veterans Affairs healthcare system 退伍军人事务医疗保健系统中无家可归和住房不稳定的服务使用者抗抑郁药物的精神药理学流行病学

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2021-11-19 DOI: 10.1002/hup.2829

Jack Tsai, Dorota Szymkowiak, Theddeus Iheanacho

Objective

This study conducted a pharmacoepidemiologic examination of antidepressant prescription patterns in homeless and unstably housed (HUH) populations.

Methods

Data were analyzed on over 2.6 million veterans from the U.S. Department of Veterans Affairs (VA), the largest provider of healthcare for HUH veterans and a system that does not require healthcare insurance.

Results

Multivariable analyses revealed that HUH veterans with depression and PTSD were less likely to receive an antidepressant Rx compared to their stably housed (SH) counterparts with these conditions (OR = 0.77, 99% CI = 0.74–0.79; and OR = 0.87, 99% CI = 0.84–0.90, respectively). Antidepressants were mostly prescribed in specialty mental health care settings, but HUH veterans were less likely to be prescribed antidepressants in primary care settings than SH veterans. In the total sample, the 40–49 age group, female sex, VA service-connected disability, outpatient mental health visits, and emergency department visits were positively associated with any antidepressant Rx. Nearly all psychiatric diagnoses were more associated with prescription of selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRIs/SNRIs) than tricyclic antidepressants.

Conclusion

These findings highlight socioeconomic disparities in antidepressant Rx in a healthcare system that does not rely on insurance and suggest clinical challenges with antidepressant prescriptions in HUH populations.

目的对无家可归和住房不稳定人群的抗抑郁药物处方模式进行药物流行病学调查。方法分析来自美国退伍军人事务部(VA)的260多万退伍军人的数据，VA是HUH退伍军人最大的医疗保健提供者，也是一个不需要医疗保险的系统。结果多变量分析显示，与稳定居住(SH)的退伍军人相比，患有抑郁症和PTSD的HUH退伍军人接受抗抑郁药Rx的可能性更低(OR = 0.77, 99% CI = 0.74-0.79;和= 0.87,99% CI -0.90 = 0.84,分别)。抗抑郁药主要在专业精神卫生保健机构开，但HUH退伍军人在初级保健机构开抗抑郁药的可能性低于SH退伍军人。在总样本中，40-49岁年龄组、女性、退伍军人事务部服务相关的残疾、门诊精神健康就诊和急诊就诊与任何抗抑郁药处方呈正相关。几乎所有的精神病诊断都与选择性5 -羟色胺再摄取抑制剂/ 5 -羟色胺和去甲肾上腺素再摄取抑制剂(SSRIs/SNRIs)的处方相关，而不是三环抗抑郁药。这些发现突出了在不依赖保险的医疗保健系统中抗抑郁药物处方的社会经济差异，并提示了在HUH人群中抗抑郁药物处方的临床挑战。

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引用次数: 1

Stress, caffeine and psychosis-like experiences—A double-blind, placebo-controlled experiment 压力、咖啡因和精神病样经历——一项双盲、安慰剂对照实验

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2021-11-18 DOI: 10.1002/hup.2828

Csilla Ágoston, László Bernáth, Peter J. Rogers, Zsolt Demetrovics

Objective

Psychosis-like perceptual distortions can occur in the general population, and both stress and caffeine can enhance the proneness to psychosis-like experiences, such as hallucinations. The current study aims to explore the effects of acute caffeine intake and acute stress on perceptual distortions in a double-blind, placebo-controlled experiment.

Methods

Regular caffeine consumers (n = 92) and non/low consumers (n = 89) were assigned to 100 mg caffeine/placebo and stress/no stress conditions. The White Christmas Paradigm (WCP) was used to measure hallucination-like symptoms, and bias towards threat-related words was used as an indicator of persecutory ideation. Participants reported their daily caffeine intake, and completed the State-Trait Anxiety Inventory, the Launay-Slade Hallucination Scale, the Persecutory Ideation Questionnaire and the Marlow-Crowne Social Desirability Scale.

Results

Acute stress slightly increased hallucination-like experiences, but not recall bias, while the small amount of caffeine had a time-dependent effect on recall bias. Proneness to persecutory ideation was positively and social desirability was negatively correlated with recall bias towards threat-related words, while proneness to hallucinations positively correlated with hallucination-like experiences.

Conclusions

Our results indicate that psychosocial stress—in line with the diathesis–stress model—can lead to the enhancement of hallucination-like experiences.

一般人群都可能出现类似精神病的知觉扭曲，压力和咖啡因都可以增加类似精神病的经历的倾向，比如幻觉。本研究旨在通过双盲安慰剂对照实验，探讨急性咖啡因摄入和急性应激对知觉扭曲的影响。方法将常规咖啡因摄入者(n = 92)和非/低咖啡因摄入者(n = 89)分为100 mg咖啡因/安慰剂组和应激/无应激组。白色圣诞范式(WCP)用于测量幻觉样症状，对威胁相关词汇的偏见被用作迫害意念的指标。参与者报告了他们每天的咖啡因摄入量，并完成了状态-特质焦虑量表、劳奈-斯莱德幻觉量表、受迫害意念问卷和马洛-克朗社会期望量表。结果急性应激轻微增加幻觉样体验，但不增加回忆偏倚，而少量咖啡因对回忆偏倚有时间依赖性。受迫害意念倾向与威胁相关词语的回忆偏向呈正相关，社会期望倾向与威胁相关词语的回忆偏向呈负相关，而幻觉倾向与幻觉样经历呈正相关。结论心理社会应激(符合素质-应激模型)可导致幻觉样体验的增强。

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引用次数: 0

Prospective analysis of serum prolactin levels, clinical symptomatology and sexual functions in patients with schizophrenia switched to paliperidone palmitate 3-monthly from paliperidone palmitate 1-monthly: Preliminary findings of the first 3 months 从棕榈酸帕利哌酮1个月改用棕榈酸帕利哌酮3个月的精神分裂症患者血清催乳素水平、临床症状和性功能的前瞻性分析:前3个月的初步结果

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2021-11-17 DOI: 10.1002/hup.2827

Ersin Hatice Karslioğlu, Zeynep Kolcu, Nisa İrem Karslioğlu, Ali Çayköylü

Objective

Long-acting injectable (LAI) antipsychotics were developed to improve adherence to schizophrenia treatment. Paliperidone palmitate (PP) has two LAI forms: Monthly (PP1M) and three-monthly (PP3M). PP3M shows less difference in Peak-to-Trough drug concentration levels. This could be related to a lower incidence of hyperprolactinemia, which may negatively affect adherence. We aimed to compare prolactin levels and investigate relationships between prolactin levels, symptomatology and sexual function in patients with schizophrenia after switching from PP1M to PP3M.

Methods

Twenty-five patients were enrolled. The sociodemographic data form, the Positive and Negative Syndromes Scale (PANSS) and the Arizona Sexual Experience Scale (ASEX) were used. Morning blood samples were drawn to determine prolactin levels.

Results

Prolactin level (p < 0.001), the total score and arousal sub-score of ASEX (respectively; p = 0.015, p = 0.020) and the total score and positive scale of PANSS (respectively; p = 0.017, p = 0.021) were decreased on the 90th day (±15 days).

Conclusions

After switching to PP3M, the decreases in prolactin levels and potentially related sexual side effects was statistically significant. There may be a difference between two formulations of the same drug in terms of side effects, and there is a need for prospective follow-up studies with larger samples.

目的研制长效注射抗精神病药物，提高精神分裂症治疗的依从性。棕榈酸帕利哌酮(PP)有两种LAI形式:每月(PP1M)和三个月(PP3M)。PP3M在峰谷药物浓度水平上差异较小。这可能与高泌乳素血症发生率较低有关，这可能对依从性产生负面影响。我们的目的是比较催乳素水平，并研究精神分裂症患者从PP1M转为PP3M后催乳素水平、症状和性功能之间的关系。方法入选25例患者。采用社会人口学数据表、阳性和阴性症状量表(PANSS)和亚利桑那性经验量表(ASEX)。早上抽取血样以测定催乳素水平。结果催乳素水平(p <0.001)， ASEX总分和唤醒分值分别为;p = 0.015, p = 0.020)， PANSS总分和阳性量表分别为;P = 0.017, P = 0.021)在第90天(±15天)下降。结论改用PP3M后，催乳素水平下降及相关的性副作用均有统计学意义。同一药物的两种剂型在副作用方面可能存在差异，因此需要对更大样本进行前瞻性随访研究。

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引用次数: 3

Influence of eight ABCB1 polymorphisms on antidepressant response in a prospective cohort of treatment-free Russian patients with moderate or severe depression: An explorative psychopharmacological study with naturalistic design 8种ABCB1多态性对俄罗斯中重度抑郁症患者无治疗前瞻性队列抗抑郁反应的影响:一项自然设计的探索性精神药理学研究

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2021-11-17 DOI: 10.1002/hup.2826

Lisanne M. Geers, Taichi Ochi, Natalya M. Vyalova, Innokentiy S. Losenkov, Diana Z. Paderina, Ivan V. Pozhidaev, German G. Simutkin, Nikolay A. Bokhan, Bob Wilffert, Daniël J. Touw, Anton J.M. Loonen, Svetlana A. Ivanova

Background

Many antidepressants are substrates of P-glycoprotein, an efflux transporter in the blood-brain-barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response.

Method

152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton-Depression-Rating-Scale (HAMD-17)-scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene-polymorphisms and reduction in HAMD-17 score were assessed using independent t-test and multiple linear regression.

Results

Tricyclic antidepressants were associated with a higher reduction of HAMD-17 score when compared to SSRIs. The SNP rs2235040 A-allele had a significant positive influence on the ΔHAMD-17_(0→2W) score but a significant negative influence on the ΔHAMD-17_(2→4W) score. The rs4148739 G-allele had a significant negative influence on the ΔHAMD-17_(0→2W) score but a significant positive influence on the ΔHAMD-17_(2→4W) score. The SNP rs2235015 T-allele is significant negatively related to the ΔHAMD-17_(2→4W) score.

Conclusion

ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.

许多抗抑郁药是p -糖蛋白的底物，p -糖蛋白是一种由ABCB1基因编码的血脑屏障外排转运蛋白。遗传变异可能影响抗抑郁药的转运率，从而影响其药理作用。本研究探讨了ABCB1基因的8个多态性对抗抑郁治疗反应的影响。方法选取托木斯克市精神卫生研究所精神科收治的152例患者。汉密尔顿抑郁评定量表(HAMD-17)得分在基线和第二周、第二周和第四周、基线和第四周之间的差异被用来估计抑郁症改善的时间。采用独立t检验和多元线性回归评估ABCB1基因多态性与HAMD-17评分降低之间的关系。结果与SSRIs相比，三环类抗抑郁药与HAMD-17评分的降低相关。SNP rs2235040 a等位基因对ΔHAMD-17(0→2W)评分有显著的正影响，对ΔHAMD-17(2→4W)评分有显著的负影响。rs4148739 g等位基因对ΔHAMD-17(0→2W)评分有显著负向影响，对ΔHAMD-17(2→4W)评分有显著正向影响。SNP rs2235015 t等位基因与ΔHAMD-17(2→4W)评分呈显著负相关。结论ABCB1基因变异影响抗抑郁药物反应的速度，但不影响其程度。

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引用次数: 3

The potential role of lysergic acid diethylamide for psychological assisted therapy: A meta-analysis of randomised controlled trials in healthy volunteers 麦角酸二乙胺在心理辅助治疗中的潜在作用:一项健康志愿者随机对照试验的荟萃分析

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental

Pub Date : 2021-11-05 DOI: 10.1002/hup.2825

Hang Li, Yi Zhong, Siyuan Yang, Jiahe Wang, Xiang Li, Jianguo Xu, Heng Gao, Gang Chen

Objective

In recent years, interest in using lysergic acid diethylamide (LSD) in psychiatric research and corresponding therapy has increased rapidly. In this meta-analysis, we explored the effects of LSD on healthy subjects with respect to subjective drug effects, blood pressure, heart rate, body temperature and side effects.

Method

PubMed, Embase, and the Cochrane Library were searched from January 2010 to December 2020 for randomized controlled trials (RCTs) on the effects of LSD in healthy people. Subsequently, 5 RCTs with 132 healthy people which focused on the effects of LSD were enrolled in our study.

Result

We found that taking 50, 100 and 200 mcg LSD doses were associated with a significant increase in the maximal difference from the baseline compared to the placebo group among the outcomes of AMRS (Adjective Mood Rating Scale) score. Significant differences existed between the LSD and placebo groups when taking 100 and 200 mcg LSD in acute adverse effects (100 mcg: SMD = .97, 95% confidence interval [CI], .50, 1.44, Z = 4.04, p < .001; 200 mcg: SMD = 1.18, 95% CI, 0.65, 1.72, Z = 4.32, p < .001).

Conclusions

Meta-analysis of the subjective effects of LSD in healthy people revealed moderate significant effect sizes in favor of LSD with no significant adverse effects. A 100 mcg dose of LSD has potential for use in psychological-assisted therapy and may improve the mental fitness of patients with disease-related psychiatric distress. Additional clinical trials are necessary to explore the efficacy and safety of LSD as a psychological-assisted therapy.

目的近年来，人们对麦角酸二乙基酰胺(LSD)在精神病学研究和治疗中的应用兴趣迅速增加。在本荟萃分析中，我们探讨了LSD对健康受试者在主观药物效应、血压、心率、体温和副作用方面的影响。方法检索PubMed、Embase和Cochrane图书馆2010年1月至2020年12月关于LSD对健康人影响的随机对照试验(rct)。随后，我们的研究纳入了5项随机对照试验，涉及132名健康人，主要关注LSD的影响。结果我们发现，与安慰剂组相比，服用50、100和200 mcg LSD剂量组的AMRS(形容词情绪评定量表)评分结果与基线的最大差异显著增加。服用100 mcg和200 mcg LSD与安慰剂组在急性不良反应方面存在显著差异(100 mcg: SMD = 0.97, 95%可信区间[CI]， 0.50, 1.44, Z = 4.04, p <措施;200 mcg: SMD = 1.18, 95% CI, 0.65, 1.72, Z = 4.32, p & lt;措施)。结论LSD对健康人主观效应的荟萃分析显示，LSD具有中等显著效应，无显著不良反应。100微克剂量的LSD有可能用于心理辅助治疗，并可能改善与疾病相关的精神痛苦患者的心理健康。进一步的临床试验是必要的，以探索LSD作为一种心理辅助治疗的有效性和安全性。

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引用次数: 4