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How the Food and Drug Administration Drug Approval Process Relates to the Potential Approval of Intravenous Racemic Ketamine for Treatment-resistant Major Depression. 美国食品和药物管理局的药物审批程序如何与可能批准静脉注射消旋氯胺酮治疗耐药性重度抑郁症相关联。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000768
Sheldon H Preskorn

This column focuses on the status of intravenous racemic ketamine for the treatment of patients suffering from a form of major depressive disorder that does not respond to trials of currently available biogenic amine antidepressants. To provide context, the column reviews the 3 pivotal elements of the usual Food and Drug Administration (FDA) drug approval process: (1) the unmet medical need (ie, the indication) for which the drug is being developed, (2) the efficacy of the drug for that condition, and (3) the safety/tolerability of the drug. This column is based on the author's 45-year history of drug development work and is not a statement of the FDA. There are typically 3 phases in the drug development process: (1) studies done in normal volunteers, (2) typically small-scale proof of concept studies, and (3) large-scale registration trials. This third phase is critical in determining the efficacy, safety, and tolerability of the drug in a manner that most closely follows the clinical use of the drug. This column focuses specifically on whether generally small-scale studies done in academic centers are sufficient for drug approval, and it briefly reviews lithium and clozapine as examples of psychiatric medications that had such academic research in the literature, as well as clinical use in other countries. Those data supported the unique value of these medications in patients with bipolar disorder and treatment-resistant schizophrenia (ie, the unmet medical need), respectively, and the findings led American psychiatrists to advocate for FDA approval of these medications. Their efforts led to the needed registration trials for FDA approval of these medications. This column reviews the key features of registration trials and the reason that they are critical for FDA approval, and it discusses 2 special considerations related to the intravenous administration of racemic ketamine. First, racemic ketamine is not esketamine but, instead, it contains R-ketamine in addition to S-ketamine (ie, esketamine). The second consideration is that differences between intravenous and intranasal administration may affect the safety of the drug. While safety concerns were specifically addressed in the registration trials for esketamine, comparable research remains to be done for intravenous racemic ketamine. Understanding how the FDA's drug approval process works is important for prescribers, their patients, and the public.

本专栏主要介绍静脉注射外消旋氯胺酮治疗重度抑郁症患者的情况,这种患者对目前可用的生物胺类抗抑郁药试验无反应。为了提供背景资料,本专栏回顾了美国食品和药物管理局(FDA)通常药物审批程序的三个关键要素:(1)正在开发的药物尚未满足的医疗需求(即适应症);(2)药物对该病症的疗效;以及(3)药物的安全性/耐受性。本专栏基于作者 45 年的药物开发工作经验,并非 FDA 的声明。药物开发过程通常分为 3 个阶段:(1)在正常志愿者中进行的研究;(2)典型的小规模概念验证研究;(3)大规模注册试验。第三阶段对于以最贴近临床用药的方式确定药物的疗效、安全性和耐受性至关重要。本专栏特别关注在学术中心进行的一般小规模研究是否足以作为药物审批的依据,并简要回顾了锂和氯氮平作为精神科药物的例子,这些药物在文献中进行了此类学术研究,并在其他国家进行了临床使用。这些数据分别支持了这些药物在双相情感障碍和耐药性精神分裂症患者中的独特价值(即未满足的医疗需求),这些研究结果促使美国精神科医生倡导美国食品药物管理局批准这些药物。他们的努力促成了 FDA 批准这些药物所需的注册试验。本专栏回顾了注册试验的主要特点以及注册试验对 FDA 批准至关重要的原因,并讨论了与外消旋氯胺酮静脉注射有关的两个特殊注意事项。首先,外消旋氯胺酮不是艾司氯胺酮,而是除了 S-氯胺酮(即艾司氯胺酮)外还含有 R-氯胺酮。第二个考虑因素是静脉注射和鼻内注射的不同可能会影响药物的安全性。虽然在埃斯氯胺酮的注册试验中专门讨论了安全性问题,但对于静脉注射外消旋氯胺酮仍有待进行类似的研究。了解美国食品和药物管理局的药物审批程序对处方者、患者和公众都很重要。
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引用次数: 0
Formulary Coverage of Esketamine and Ketamine for Depression in Ohio Health Insurance Marketplace and Medicaid Plans. 俄亥俄州健康保险市场和医疗补助计划中治疗抑郁症的 Esketamine 和 Ketamine 的处方覆盖范围。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000766
Brian S Barnett

For more than 2 decades, intravenous ketamine has been demonstrated to have rapid antidepressant effects. However, access to this generic drug is limited due to insurers claiming it is "experimental" because ketamine does not have a Food and Drug Administration indication for depression. In contrast, intranasal esketamine, an enantiomer of ketamine, is approved by the Food and Drug Administration for depression and is still under patent. The goal of this column is to provide a clearer understanding of formulary coverage of these similar medications by insurers. Formularies of all 2023 Ohio Health Insurance Marketplace and Medicaid plans were reviewed to determine the inclusion status of intravenous ketamine and intranasal esketamine for depression. This review found that intravenous ketamine was not covered by any Marketplace or Medicaid plan for depression, while intranasal esketamine was on 72.7% and 100% of formularies, respectively. Thus, members of the analyzed insurance plans can more easily access intranasal esketamine than intravenous ketamine for depression, despite the latter being more cost-effective and possibly more efficacious.

二十多年来,静脉注射氯胺酮已被证明具有快速抗抑郁作用。然而,由于保险公司声称氯胺酮是 "试验性 "药物,因此这种非专利药物的使用受到了限制,因为氯胺酮并没有获得美国食品药品管理局的抑郁症适应症。与此相反,氯胺酮的对映体--鼻内注射用艾司氯胺酮已被美国食品药品管理局批准用于治疗抑郁症,并且仍在专利期内。本专栏旨在让读者更清楚地了解保险公司对这些类似药物的处方覆盖范围。我们审查了 2023 年俄亥俄州健康保险市场和医疗补助计划的所有医保目录,以确定静脉注射氯胺酮和鼻内注射艾司氯胺酮治疗抑郁症的纳入情况。审查发现,静脉注射氯胺酮未被任何市场或医疗补助计划纳入抑郁症治疗范围,而鼻内注射艾司氯胺酮则分别被纳入 72.7% 和 100% 的医保目录。因此,与静脉注射氯胺酮相比,分析的保险计划的成员更容易获得鼻内注射艾司氯胺酮治疗抑郁症,尽管后者更具成本效益,疗效也可能更好。
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引用次数: 0
Prodromal or Factitious Psychosis: A Cautionary Tale in the Era of Increasing Social Media Use by Vulnerable Individuals. 前驱性或假性精神病:在弱势群体越来越多地使用社交媒体的时代,一个值得警惕的故事。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000771
Leo Bastiaens, Stephanie Cristofano-Casella, Jesse Bastiaens

Research on the prodromal phase of schizophrenia has been ongoing for several decades and, more recently, findings from this research are being incorporated into everyday psychiatric practice, such as the use of interviews to evaluate prodromal symptomatology. This evolution is happening in the midst of an explosion of social media use by teenagers and young adults, increasing the exposure of youth to portrayals of psychiatric experiences. For example, reports from around the world of "TIK-TOK tics" emphasize the role of social media in the "creation" of psychiatric symptoms. This case report highlights the importance of a full psychiatric evaluation in acute care settings where quick treatment of psychotic symptoms is the norm. A 15-year-old patient was initially diagnosed with prodromal schizophrenia but, after a more extensive evaluation during a second admission, she was diagnosed with borderline personality disorder. Her antipsychotic treatment regimen was stopped and appropriate education and treatment were started, without the recurrence of "psychotic symptoms" during follow-up. It may be that patients with borderline personality disorder, a frequent condition on inpatient units, are at particular risk of assimilating symptoms as represented on social media.

对精神分裂症前驱期的研究已经持续了几十年,最近,这项研究的结果正在被纳入日常的精神科实践中,例如使用访谈来评估前驱期症状。这一演变是在青少年使用社交媒体激增的背景下发生的,社交媒体增加了青少年接触精神科经历的机会。例如,世界各地关于 "TIK-TOK 抽搐 "的报道强调了社交媒体在 "创造 "精神症状中的作用。本病例报告强调了在急症护理环境中进行全面精神评估的重要性,因为在急症护理环境中,快速治疗精神病症状是一种常态。一名 15 岁的患者最初被诊断为前驱型精神分裂症,但在第二次入院接受更全面的评估后,她被诊断为边缘型人格障碍。她的抗精神病治疗方案被停止,并开始接受适当的教育和治疗,但在随访期间没有再出现 "精神病症状"。边缘型人格障碍是住院病房的常见病,边缘型人格障碍患者可能特别容易吸收社交媒体上的症状。
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引用次数: 0
Acknowledgment of Peer Reviewers. 感谢同行评审员。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000777
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引用次数: 0
Patterns of Psychiatric Medication Prescriptions for Veterans in Treatment Courts and Other Specialty Courts. 治疗法庭和其他专业法庭为退伍军人开具精神病药物处方的模式。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000769
Jack Tsai, Nicholaus J Christian, Dorota Szymkowiak

Psychiatric medications can serve as important tools for addressing behavioral health issues among criminal justice-involved (CJI) veterans. This study used national data on 12,790 CJI veterans in the U.S. Department of Veterans Affairs (VA) Veterans Justice Outreach program from 2019 to 2020 to compare patterns of psychiatric medication prescriptions among veterans who entered a veterans treatment court (n = 6975), another specialty court (SC; n = 414), or no-SC (n = 5401). Different classes of medications were examined, including antidepressants, stimulants, antipsychotics, benzodiazepines, and medications for substance use disorders. The results showed that 60.2% of the total sample was prescribed a psychiatric medication within 1 year of entering the Veterans Justice Outreach program. There was no significant difference in overall psychiatric prescribing among veterans treatment court, other SC, and no-SC groups, but there were a few differences in certain classes of psychiatric medications. Moreover, about 7.8% of veterans who were in the no-SC group and were prescribed psychiatric medications did not have a psychiatric diagnosis. Veterans who were younger, non-Hispanic white, married, with a VA service-connected disability rating, had a diagnosis of mental and/or substance use disorder, and used more VA health care services were more likely to have been prescribed psychiatric medication. Together, these findings illustrate the essential role of psychiatric medications in courts and programs that serve CJI veterans, as well as the important link between VA service engagement and psychiatric prescriptions.

精神科药物可以作为解决涉及刑事司法(CJI)的退伍军人行为健康问题的重要工具。本研究使用了美国退伍军人事务部(VA)退伍军人司法外展项目在 2019 年至 2020 年期间收集的 12790 名参与刑事司法调查的退伍军人的全国数据,比较了进入退伍军人治疗法庭(n = 6975)、其他专业法庭(SC;n = 414)或无专业法庭(n = 5401)的退伍军人的精神科药物处方模式。对不同类别的药物进行了研究,包括抗抑郁药、兴奋剂、抗精神病药、苯二氮卓类药物和治疗药物使用障碍的药物。结果显示,在所有样本中,有 60.2% 的人在加入退伍军人司法外展计划后的 1 年内服用过精神科药物。退伍军人治疗法庭组、其他 SC 组和非 SC 组在开具精神科药物的总体情况上没有明显差异,但在某些精神科药物类别上存在一些差异。此外,在无 SC 组别中,约有 7.8% 的退伍军人在被开具精神病药物处方时没有精神病诊断。年龄较轻、非西班牙裔白人、已婚、有退伍军人事务部认定的伤残等级、有精神和/或药物使用障碍诊断、使用退伍军人事务部医疗服务较多的退伍军人更有可能被处方精神科药物。这些发现共同说明了精神科药物在法院和服务于CJI退伍军人的项目中的重要作用,以及退伍军人服务参与和精神科处方之间的重要联系。
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引用次数: 0
The American Psychiatric Association Publishing Textbook of Geriatric Psychiatry, Sixth Edition. 美国精神病学协会出版的《老年精神病学教科书》第六版。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000765
Matthew J Biller, Art Walaszek
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引用次数: 0
The Moral Dimension of Mental Health Treatment. 心理健康治疗的道德维度。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000775
John R Peteet

Patients regularly bring value-laden concerns to treatment, but clinicians are often unsure about what role to play in their patients' moral lives. Addressing problems in moral functioning depends on assessing how individuals are accomplishing basic moral tasks: developing moral commitments, making moral decisions, implementing these decisions, assessing the correspondence between their ideals and behavior, dealing effectively with moral failure, and developing morally admirable character traits, or virtues. Clarity about the moral dimension of clinical work is important for shaping the direction of treatment, achieving clinical aims, and engaging the moral challenges that clinicians face.

病人在接受治疗时经常会提出一些价值方面的问题,但临床医生往往不知道应该在病人的道德生活中扮演什么角色。解决道德功能方面的问题取决于评估个人如何完成基本的道德任务:制定道德承诺、做出道德决定、执行这些决定、评估理想与行为之间的对应关系、有效处理道德失败以及发展道德上令人钦佩的性格特征或美德。明确临床工作的道德维度对于确定治疗方向、实现临床目标以及应对临床医生面临的道德挑战非常重要。
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引用次数: 0
Attunement. 调适。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-03-01 DOI: 10.1097/PRA.0000000000000774
John M Oldham
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引用次数: 0
Characterization of Psychiatric Inpatients: The Role of Gender Differences in Clinical and Pharmacological Patterns. 精神病住院患者的特征:性别差异在临床和药物治疗模式中的作用。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-01-01 DOI: 10.1097/PRA.0000000000000756
Isabella Berardelli, Andrea Aguglia, Andrea Amerio, Salvatore Sarubbi, Elena Rogante, Maria A Trocchia, Davide Zelletta, Ludovica Longhini, Denise Erbuto, Fabrizio Pastorino, Dorian A Lamis, Marco Innamorati, Gianluca Serafini, Maurizio Pompili

Background: Severe mental disorders that require hospitalization are disabling conditions that contribute to the burden of mental diseases. They pose increased clinical challenges and highlight the need to thoroughly explore variables emerging from daily clinical practice. In this study, we assessed to what extent gender differences may characterize a large population of psychiatric inpatients.

Methods: We conducted a cross-sectional study in 2 Italian teaching medical centers, which included 2358 patients who were consecutively admitted to the psychiatric emergency units. We explored and characterized gender differences for variables such as prevalence of psychiatric diagnosis, presence of suicidal ideation, suicide attempts, age at onset of psychiatric illness, presence of substance or alcohol abuse, length of stay, number of hospitalizations, presence of involuntary admission, type of discharge from the hospital, and pharmacological treatment at discharge.

Results: Female patients were primarily diagnosed with bipolar disorder or personality disorders. Female patients had a significantly higher prevalence of lifetime suicide attempts (23.1% vs. 16.5%, P<0.001) and a longer length of hospitalization (11.43±10.73 d vs. 10.52±10.37 d, t=-2.099, gl=2356, P=0.036) compared with male patients. Male patients had more involuntary admissions (25.1% vs. 19.7%, χ2=9.616, gl=1, P=0.002), more use of illicit substances (34.1% vs. 20.9%, χ2=51.084, gl=1, P<0.001), and higher rates of alcohol abuse (21.3% vs. 14.7%, χ2=17.182, gl=1, P<0.001) compared with female patients. Finally, antidepressants and lithium were prescribed more frequently to the female patients, whereas other mood stabilizers were more often prescribed to the male patients.

Conclusions: Our real-world results highlighted gender differences among patients with severe mental disorders admitted to psychiatric units, and suggest further investigations that may help in understanding trajectories accompanying disabling clinical conditions.

背景:需要住院治疗的严重精神障碍是一种致残性疾病,加重了精神疾病的负担。它们给临床带来了更大的挑战,并凸显了深入探究日常临床实践中出现的变量的必要性。在这项研究中,我们评估了大量精神病住院患者的性别差异特征:我们在意大利的两所教学医疗中心开展了一项横断面研究,研究对象包括连续入住精神科急诊室的 2358 名患者。我们探讨了精神病诊断率、是否有自杀意念、自杀未遂、精神病发病年龄、是否滥用药物或酒精、住院时间、住院次数、是否非自愿入院、出院类型以及出院时的药物治疗等变量的性别差异及其特征:女性患者主要被诊断为躁郁症或人格障碍。女性患者终生自杀未遂的比例明显更高(23.1% vs. 16.5%,PConclusions):我们在现实世界中的研究结果突显了入住精神科的严重精神障碍患者的性别差异,并建议开展进一步调查,以帮助了解伴随致残性临床症状的轨迹。
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引用次数: 0
Patient and Caregiver Depression in Jordan After a First Stroke. 约旦首次中风后患者和护理人员的抑郁症。
IF 1.9 4区 医学 Q3 PSYCHIATRY Pub Date : 2024-01-01 DOI: 10.1097/PRA.0000000000000754
Belal Aldabbour, Majdi Al Qawasmeh, Samah Elamassie, Amal Abuabada, Khalid Abdelrahman, Mohammad Zahran, Mays Khweileh, Khalid El-Salem

Background: Poststroke depression among patients is well-recognized, while caregiver depression is understudied. The interaction between patient and caregiver depression is also unclear.

Methods: This cross-sectional and follow-up study recruited 108 patient-caregiver dyads after the first-ever stroke. Demographic and clinical data, stroke severity (NIH Stroke Scale score), functional outcome (Barthel Index), and residual disability (modified Rankin Score) were documented. Using the self-reported Patient Health Questionnaire-9, we screened patients and caregivers for depressive symptoms upon admission and after 1 month. Changes in the prevalence and severity of depression were calculated. The Pearson correlation test and logistic regression analysis were conducted to evaluate both the correlation between both groups and significant predictors of depression.

Results: In total, 89 patients and 96 caregivers responded to both screenings. Depression was reported by 13.5% and 27.0% of patients on admission and after 1 month, and 9.4% and 18.8% of caregivers, respectively. Caregiver depression on admission was significantly correlated with patient depression on admission (P=0.031). In addition, depression in caregivers after 1 month was a significant predictor of patient depression (P=0.008). Predictors of caregiver depression after 1 month were female caregivers (P=0.026), caring for a male patient (P=0.045), higher mRS scores after 1 month (P=0.013), longer admissions (P=0.017), caregiver between 17 and 35 years of age compared with 54 to 70 years of age (P=0.030), and caring for a patient with poststroke depression at 1 month poststroke (P=0.003).

Conclusions: Both stroke survivors and their caregivers are at high risk for depression, with a potential interaction between depression in the 2 groups.

背景:卒中后患者抑郁已得到广泛认可,而护理者抑郁却未得到充分研究。患者抑郁与护理者抑郁之间的相互作用也不清楚:方法:这项横断面和随访研究招募了 108 例首次中风后患者-护理者二人组。记录了人口统计学和临床数据、中风严重程度(NIH 中风量表评分)、功能结果(Barthel 指数)和残障程度(修正的 Rankin 评分)。我们使用自我报告的《患者健康问卷-9》对患者和护理人员进行了入院时和入院 1 个月后的抑郁症状筛查。我们计算了抑郁症患病率和严重程度的变化。通过皮尔逊相关性检验和逻辑回归分析来评估两组之间的相关性和抑郁症的重要预测因素:共有 89 名患者和 96 名护理人员对两次筛查做出了回应。入院时和一个月后,分别有 13.5% 和 27.0% 的患者和 9.4% 和 18.8% 的护理人员报告患有抑郁症。护理人员入院时的抑郁情绪与患者入院时的抑郁情绪有明显的相关性(P=0.031)。此外,1 个月后护理人员的抑郁也是患者抑郁的重要预测因素(P=0.008)。1 个月后照护者抑郁的预测因素包括:女性照护者(P=0.026)、照护男性患者(P=0.045)、1 个月后 mRS 评分较高(P=0.013)、入院时间较长(P=0.017)、照护者年龄在 17-35 岁之间(P=0.030)与 54-70 岁之间(P=0.030)之间、照护卒中后 1 个月抑郁的患者(P=0.003):结论:卒中幸存者及其照护者都是抑郁症的高危人群,这两类人群的抑郁症之间可能存在相互作用。
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引用次数: 0
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Journal of Psychiatric Practice
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