From the Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
J Clin Psychopharmacol. 2022;42(5 Suppl 1):S1-S13. doi: 10.1097/JCP.0000000000001596.
This continuing education supplement is jointly provided by Medical Education Resources and CMEology. The supplement is supported by an independent educational grant from Sunovion Pharmaceuticals Inc. It was edited and peer reviewed by the Journal of Clinical Psychopharmacology.After reviewing the learning objectives and reading the supplement, please complete the Activity Evaluation/Credit Request form online at https://www.cmesurvey.site/TAAR1.
All currently available antipsychotics work via essentially the same mechanism: by antagonizing the dopamine D2 receptor. However, schizophrenia is an extremely heterogeneous condition, and antipsychotics do not adequately control symptoms for all patients. Negative and cognitive symptoms are especially difficult to manage with existing medications. Therefore, antipsychotic agents with novel mechanisms of action are urgently needed. Recently, a phase 2 clinical trial and extension study demonstrated that, relative to placebo, the trace amine-associated receptor 1 (TAAR1) agonist ulotaront was effective at controlling the positive, negative, and cognitive symptoms of schizophrenia. In addition, ulotaront seems to lack the weight gain, metabolic issues, and extrapyramidal symptoms associated with traditional antipsychotics. This agent is currently undergoing multiple phase 3 trials for the treatment of schizophrenia. Another TAAR1 agonist, ralmitaront, is being investigated for the treatment of schizophrenia and schizoaffective disorders. Two phase 2 clinical trials are underway, evaluating ralmitaront both as a monotherapy and an add-on therapy to traditional antipsychotics. In this supplement, we review the biologic, preclinical, and clinical data available for TAAR1 agonists, so that if and when they are approved for the treatment of schizophrenia, psychiatry specialists will be ready to use them to optimize patient outcomes. We also briefly review other emerging therapies in late-stage development for the treatment of schizophrenia.
本继续教育增刊由 Medical Education Resources 与 CMEology 联合提供。该增刊由 Sunovion 制药公司提供独立教育资助。它由《临床精神药理学杂志》编辑和同行评审。在审查学习目标并阅读增刊后，请在 https://www.cmesurvey.site/TAAR1 在线填写活动评估/学分申请表。
目前所有的抗精神病药物基本上都是通过相同的机制发挥作用：通过拮抗多巴胺 D2 受体。然而，精神分裂症是一种极其异质的疾病，抗精神病药物并不能使所有患者的症状都得到充分控制。阴性和认知症状尤其难以用现有药物治疗。因此，迫切需要具有新作用机制的抗精神病药物。最近，一项 2 期临床试验和扩展研究表明，与安慰剂相比，痕量胺相关受体 1（TAAR1）激动剂 ulotaront 可有效控制精神分裂症的阳性、阴性和认知症状。此外，ulotaront 似乎缺乏与传统抗精神病药物相关的体重增加、代谢问题和锥体外系症状。该药物目前正在进行多项 3 期临床试验，用于治疗精神分裂症。另一种 TAAR1 激动剂 ralmitaront 正在研究用于治疗精神分裂症和分裂情感障碍。两项 2 期临床试验正在进行，评估 ralmitaront 作为单一疗法和传统抗精神病药物的附加疗法的疗效。在本增刊中，我们回顾了 TAAR1 激动剂的生物学、临床前和临床数据，以便在它们被批准用于治疗精神分裂症时，精神科专家能够准备好使用它们来优化患者的治疗效果。我们还简要回顾了其他处于后期开发阶段的治疗精神分裂症的新兴疗法。
