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Ketamine in depression

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Ketamine in depression

Ketamine is noncompetitive voltage-dependent N-methyl-D-aspartate receptor channel blocker whose antidepressant action is evident at low doses, and with increasing doses, it mimics psychotomimetic action and eventually leads to anesthesia in higher doses (1)

  • single dose of ketamine has rapid action on depressive symptoms, and this action persists even for a week, which suggests its possible role in neuroplasticity
  • ketamine may provide a rapid, robust, but transient antidepressant effect in MDD (major depressive disorder) and BD (bipolar depression)
    • benefits of ketamine are transient, up to 1-2 weeks after infusion (2)

  • most common physical adverse effects of ketamine are dizziness, blurred vision, headache, nausea or vomiting, dry mouth, poor coordination, poor concentration and restlessness (3)
    • effects have mostly been restricted to the time of administration, usually resolving within 60 minutes

  • the Royal College of Psychiatrists have stated (3)
    • there is limited evidence to recommend ketamine as a viable treatment option for treatment resistant depression
      • a systematic review found non-significant trend for ECT superiority over ketamine for post-treatment depression ratings (4)
    • short term efficacy has been demonstrated after a single treatment, but benefits are not lasting for most patients, and mood can rapidly decline after initial improvement, potentially increasing suicide risk

  • repeated subcutaneous ketamine injections for treatment-resistant depression (TRD)
    • the authors of the KADS study concluded that (5):
      • adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period

Mode of action (6)

  • is hypothesized that, at sub-anesthetic doses, ketamine causes an antidepressant effect through glutamatergic modulation
    • has been proposed to facilitate the neuroplasticity involved in new memory formation, fear extinction, and the restructuring of traumatic memorie
    • suggested that the psychoactive properties of sub-anesthetic ketamine doses may facilitate psychotherapeutic processes


  1. Mandal S, Sinha VK, Goyal N. Efficacy of ketamine therapy in the treatment of depression. Indian J Psychiatry. 2019 Sep-Oct;61(5):480-485.
  2. Corriger A, Pickering G. Ketamine and depression: a narrative review. Drug Des Devel Ther. 2019 Aug 27;13:3051-3067.
  3. Royal College of Psychiatrists (February 2017). Statement on ketamine to treat depression
  4. Menon V, Varadharajan N, Faheem A, Andrade C. Ketamine vs Electroconvulsive Therapy for Major Depressive Episode: A Systematic Review and Meta-analysis. JAMA Psychiatry. Published online April 12, 2023. doi:10.1001/jamapsychiatry.2023.0562
  5. Loo, C et al (2023). Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): Randomised double-blind active-controlled trial. The British Journal of Psychiatry, 1-9. doi:10.1192/bjp.2023.79
  6. Njenga C, Ramanuj P P, de Magalhães F J C, Pincus H A. New and emerging treatments for major depressive disorder BMJ 2024; 386 :e073823 doi:10.1136/bmj-2022-073823

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