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Ketamine for depression

Jolien K E Veraart

February 10, 2026 DOI: 10.33612/diss.1484805904 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Thesis including a randomized controlled trial, survey, and real-world clinical practice observations
Population People with treatment-resistant depression
Interventions oral esketamine ketamine psychotherapy
Topics Depression Ketamine Esketamine
Keywords Electroconvulsive therapy Dosing Clinical trial Meaning existential Depression economics Randomized controlled trial Psychotherapist Intensive care medicine Dissociative
Key findings Fixed low doses of oral esketamine were not effective, but higher, individualized dosing led to meaningful improvement in a subgroup of patients.

Abstract

This thesis explores the use of ketamine in people with treatment-resistant depression. It starts by examining the concept of treatment-resistant depression, a term that is widely used but poorly defined. Importantly, this label may negatively influence patients’ expectations and sense of hope. As an alternative, more neutral framing is suggested.Survey data from individuals seeking ketamine treatment show that many have been suffering from depressive symptoms for years and are dissatisfied with standard treatments. At the same time, there is strong interest in innovative approaches. The thesis therefore focuses on the clinical potential of oral esketamine, studied both in a randomized controlled trial and in real-world clinical practice. Fixed low doses were not effective, but higher, individualized dosing led to meaningful improvement in a subgroup of patients.The thesis further examines ketamine treatment in patients with complex and comorbid forms of depression, including those with psychotic symptoms, post-traumatic stress disorder (PTSD), and patients receiving maintenance electroconvulsive therapy (ECT). In these populations, ketamine was often effective and well tolerated, particularly when provided in a supportive and carefully monitored setting. Combining ketamine with psychotherapy appears promising, although more controlled research is needed.Finally, the thesis addresses important pharmacological issues such as drug–drug interactions, the safety of combining ketamine with MAO inhibitors, and variability in blood levels. A key finding is the possible occurrence of auto-induction, meaning that repeated oral use may speed up ketamine’s own metabolism, potentially reducing its long-term effectiveness. Overall, this work offers practical guidance for the safe and thoughtful use of ketamine in clinical practice.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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