The molecular pathophysiology of depression and the new therapeutics

Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness,...

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Published inMedComm (2020) Vol. 3; no. 3; pp. e156 - n/a
Main Authors Tian, Haihua, Hu, Zhenyu, Xu, Jia, Wang, Chuang
Format Journal Article
LanguageEnglish
Published China John Wiley & Sons, Inc 01.09.2022
John Wiley and Sons Inc
Wiley
Subjects
(R)‐ketamine
(S)‐ketamine
Antidepressants
Drug therapy
Ketamine
major depressive disorder (MDD)
Mental depression
Pathophysiology
Review
Reviews
ketamine
(S)‐ketamine
major depressive disorder (MDD)
(R)‐ketamine
Online AccessGet full text

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Abstract Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long‐lasting antidepressant effects in treatment‐resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects. This review aimed to clarify the safety, tolerability, and efficacy of ketamine and its metabolites for the treatment of major depressive disorder (MDD), along with a review of potential pharmacological mechanisms, research challenges, and future clinical prospects. Many novel hubba proteins and MDD‐risk proteins were found, indicating that the current pharmacological mechanisms were just the tip of the iceberg.
AbstractList Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long-lasting antidepressant effects in treatment-resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects.Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long-lasting antidepressant effects in treatment-resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects.
Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long-lasting antidepressant effects in treatment-resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects.
Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long‐lasting antidepressant effects in treatment‐resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects. This review aimed to clarify the safety, tolerability, and efficacy of ketamine and its metabolites for the treatment of major depressive disorder (MDD), along with a review of potential pharmacological mechanisms, research challenges, and future clinical prospects. Many novel hubba proteins and MDD‐risk proteins were found, indicating that the current pharmacological mechanisms were just the tip of the iceberg.
Abstract Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long‐lasting antidepressant effects in treatment‐resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects.
Author Tian, Haihua
Hu, Zhenyu
Xu, Jia
Wang, Chuang
AuthorAffiliation 1 Ningbo Key Laboratory of Behavioral Neuroscience Ningbo University School of Medicine Ningbo Zhejiang China
4 Department of Laboratory Medicine Ningbo Kangning Hospital Ningbo Zhejiang China
5 Department of Child Psychiatry Ningbo Kanning Hospital Ningbo Zhejiang China
2 Zhejiang Provincial Key Laboratory of Pathophysiology School of Medicine Ningbo University Ningbo Zhejiang China
3 Department of Physiology and Pharmacology Ningbo University School of Medicine Ningbo Zhejiang China
AuthorAffiliation_xml – name: 2 Zhejiang Provincial Key Laboratory of Pathophysiology School of Medicine Ningbo University Ningbo Zhejiang China
– name: 4 Department of Laboratory Medicine Ningbo Kangning Hospital Ningbo Zhejiang China
– name: 3 Department of Physiology and Pharmacology Ningbo University School of Medicine Ningbo Zhejiang China
– name: 5 Department of Child Psychiatry Ningbo Kanning Hospital Ningbo Zhejiang China
– name: 1 Ningbo Key Laboratory of Behavioral Neuroscience Ningbo University School of Medicine Ningbo Zhejiang China
Author_xml – sequence: 1
  givenname: Haihua
  surname: Tian
  fullname: Tian, Haihua
  organization: Ningbo Kangning Hospital
– sequence: 2
  givenname: Zhenyu
  surname: Hu
  fullname: Hu, Zhenyu
  organization: Ningbo Kanning Hospital
– sequence: 3
  givenname: Jia
  surname: Xu
  fullname: Xu, Jia
  email: xujia@nbu.edu.cn
  organization: Ningbo University School of Medicine
– sequence: 4
  givenname: Chuang
  surname: Wang
  fullname: Wang, Chuang
  email: wangchuang@nbu.edu.cn
  organization: Ningbo University School of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35875370$$D View this record in MEDLINE/PubMed
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Issue 3
Keywords ketamine
(S)‐ketamine
major depressive disorder (MDD)
(R)‐ketamine
Language English
License Attribution
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2022 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.
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Notes Haihua Tian and Zhenyu Hu contributed equally to this work.
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Snippet Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology...
Abstract Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular...
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SubjectTerms (R)‐ketamine
(S)‐ketamine
Antidepressants
Drug therapy
Ketamine
major depressive disorder (MDD)
Mental depression
Pathophysiology
Review
Reviews
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Title The molecular pathophysiology of depression and the new therapeutics
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