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Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder

Jolien K E Veraart, M. van Westenbrugge, J.E. van Wulfften Palthe, Annemarie van der Meij, Robert A Schoevers, Joop De Jong

Heliyon May 1, 2023 DOI: 10.1016/j.heliyon.2023.e15883 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case series Case report Peer reviewed
Sample size 5
Population Patients with treatment-resistant depression and comorbid PTSD
Intervention Esketamine
Duration Six weeks to a year
Topics Depression Esketamine Ketamine PTSD
Citations 30
Key findings In four of five patients with treatment-resistant depression and comorbid PTSD, repeated oral esketamine was associated with improved depressive symptoms, increased resilience, and greater receptiveness to psychotherapy; one patient's symptoms worsened after a threatening situation during treatment. The authors propose that esketamine within a psychotherapeutic framework is promising and call for controlled trials.

Abstract

Introduction: Ketamine and its S-enantiomer esketamine are novel pharmacotherapeutic options for treatment resistant depression (TRD). There is growing evidence on the efficacy for other psychiatric disorders, including posttraumatic stress disorder (PTSD). It is hypothesized that psychotherapy may further potentiate the effects of (es)ketamine in psychiatric disorders.

Methods: Repeated oral esketamine was prescribed once or twice weekly in five patients suffering from TRD and comorbid PTSD. We describe the clinical effects of esketamine and report data from psychometric instruments and patients' perspectives.

Results: Esketamine treatment duration ranged from six weeks to a year. In four patients, we observed improvement in depressive symptoms, increased resilience and more receptiveness to psychotherapy. One patient experienced symptom worsening in response to a threatening situation during esketamine treatment, highlighting the need for a safe setting.

Discussion: (Es)ketamine treatment within a psychotherapeutic framework appears promising in patients with treatment resistant symptoms of depression and PTSD. Controlled trials are warranted to validate these results and to elucidate the optimal treatment methods.

Comparable studies

Other case reports and case series on ketamine for PTSD, most cited first.

Study Year Design Participants
Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series Veterans with co-morbid depression and PTSD 2022 Retrospective case series n = 35
Combined Effects of Nasal Ketamine and Trauma-Focused Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder: A Pilot Case Series. Individuals with chronic, treatment-resistant PTSD 2024 Pilot case series n = 3
The Effect of Ketamine-Assisted Group Therapy on Treatment-Resistant Mental Health Conditions in Firefighters: A Prospective Observational Case Series. Firefighters with mental health diagnoses 2025 Observational case series
Dramatic and persistent relief from chronic suicidality, emotional disturbances, and trauma symptomatology with oral ketamine and memantine in refractory depression with complex PTSD A 27-year-old woman with chronic recurrent depressive disorder and complex... 2024 Case report n = 1
Case Report: Successful management of psychogenic non-epileptic seizures with intranasal esketamine. Patient with treatment-resistant depression and psychogenic non-epileptic seizures 2025 Case report n = 1

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