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Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series.

Maria Pepe, Giovanni Bartolucci, Ilaria Marcelli, Alessio Simonetti, Giovanni Camardese, Marco Di Nicola, Gabriele Sani

Journal of Psychiatric Practice July 1, 2023 DOI: 10.1097/pra.0000000000000723 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case series Case report Peer reviewed
Sample size 8
Population Outpatients with chronic treatment-resistant depression
Intervention Intranasal esketamine
Duration 3 months of treatment, with assessments at baseline and after 4, 8, and 12 weeks
Measures Montgomery-Åsberg Depression Rating Scale (MADRS), Digit Symbol Substitution Test (DSST), Trail Making Test-B (TMT-B), Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), Hamilton Anxiety Rating Scale (HARS), Clinical Global Impressions Scale (CGI)
Topics Depression Ketamine Esketamine
Keywords Humans Antidepressive agents Double-blind method Cognition Depressive disorder, treatment-resistant
Key findings In eight patients with chronic treatment-resistant depression, intranasal esketamine was followed by improvements in cognitive symptoms on the DSST, TMT-B, and PDQ-D5 within the first two months, occurring before clinical antidepressant response (at least 50% decrease in baseline MADRS scores) and earlier than reductions in HARS scores. The authors suggest this indicates an additional value to esketamine's antidepressant properties.

Abstract

Background: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine.

Methods: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI).

Findings: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores.

Conclusions: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted.

Comparable studies

Other case reports and case series on esketamine for depression, most cited first.

Study Year Design Participants
Electroconvulsive Therapy, Ketamine, and Esketamine in a Patient with Major Depressive Disorder and Multiple Comorbidities: A Case Report over 10-year Treatment from Adolescence to Adulthood. A patient with treatment-resistant depression and comorbid generalized anxiety... 2025 Case report n = 1
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
Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa Patients with anorexia nervosa and a comorbid depressive disorder treated at a private... 2023 Case report n = 4
Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder Patients with treatment-resistant depression and comorbid PTSD 2023 Case series n = 5
Disembodiment and Affective Resonances in Esketamine Treatment of Depersonalized Depression Subtype: Two Case Studies. Patients with treatment resistant depression and depersonalized depression symptoms 2024 Case study n = 2

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