Ketamine in major depressive disorder: Mechanisms and future perspectives

Cheolmin Shin, Yong Ku Kim

    Research output: Contribution to journalReview articlepeer-review

    20 Citations (Scopus)


    Major depressive disorder (MDD) is a serious psychiatric illness that causes functional impairment in many people. While monoaminergic antidepressants have been used to effectively treat MDD, these antidepressants have limitations in that they have delayed onset of action and many patients remain treatment-resistant. Therefore, there is a need to develop antidepressants with a novel target, and researchers have directed their attention to the glutamatergic system. Ketamine, although developed as an anesthetic, has been found to produce an antidepressant effect at sub-anesthetic doses via N-Methyl-D-aspartic acid (NMDA) receptor blockade as well as NMDA receptor-independent pathways. A single infusion of ketamine produced rapid improvement in clinical symptoms to a considerable level and led to the resolution of serious depressive symptoms, including imminent suicidal ideation, in patients with MDD. A series of recent randomized controlled trials have provided a high level of evidence for the therapeutic efficacy of ketamine treatment in MDD and presented new insights on the dose, usage, and route of administration of ketamine as an antidepressant. With this knowledge, it is expected that ketamine treatment protocols for MDD will be established as a treatment option available in clinical practice. However, long-term safety must be taken into consideration as ketamine has abuse potential and it is associated with psychological side effects such as dissociative or psychotomimetic effects.

    Original languageEnglish
    Pages (from-to)181-192
    Number of pages12
    JournalPsychiatry Investigation
    Issue number3
    Publication statusPublished - 2020 Mar

    Bibliographical note

    Publisher Copyright:
    © 2020 Korean Neuropsychiatric Association.


    • Antidepressant
    • Ketamine
    • Major depressive disorder
    • N-Methyl-D-aspartic acid (NMDA) receptor antagonist

    ASJC Scopus subject areas

    • Psychiatry and Mental health
    • Biological Psychiatry


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