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

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.

3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report

“…The execution of TMT involves several cognitive functions as well and depends on both prefrontal and non-frontal brain region activity, although there are some differences between the two parts of the task [ 79 , 80 ]. Indeed, it has been reported that TMT-A scores can be considered a measure of attention and speed that mainly relies on visual scanning and graphomotor and visuomotor processing speed, while working memory, inhibition control, or set-switching abilities seem to be more specifically implicated in TMT-B performance [ 79 ].…”

The Patient’s Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression

“…However, the brain-derived neurotrophic factor (BDNF) has been reported among the underlying mechanisms of the association between suicidality and depression [63]. Besides the inhibition of NMDA receptors, ketamine and esketamine can exert favorable effects on neuroinflammation through the modulation of BDNF and other intracellular proteins like the mechanistic target of rapamycin complex 1 (mTORC1) [18]. Indeed, an anti-inflammatory effect has been reported for both compounds with a potential enhancement of their anti-depressive properties [64].…”

“…The effectiveness of treatments is mainly based on objective criteria and clinicians' evaluation; however, including patients' self-rated, lived experience on changes in their symptomatology might be useful to understand the perceived helpfulness of therapies and to fill the knowledge gap about treatment outcomes [14,15]. Preliminary data focusing on clinician-rated specific symptoms and psychopathological dimensions reported beneficial effects of ESK-NS on anxiety, cognition, and physical correlates, as well as on anhedonia and suicidality in TRD patients [2,[16][17][18]. However, little evidence is available on the viewpoint of patients with TRD receiving esketamine, and it has been investigated through audio interviews [19] and self-administered questionnaires assessing cognition, quality of life, and functional outcomes [18,20,21].…”

“…Preliminary data focusing on clinician-rated specific symptoms and psychopathological dimensions reported beneficial effects of ESK-NS on anxiety, cognition, and physical correlates, as well as on anhedonia and suicidality in TRD patients [2,[16][17][18]. However, little evidence is available on the viewpoint of patients with TRD receiving esketamine, and it has been investigated through audio interviews [19] and self-administered questionnaires assessing cognition, quality of life, and functional outcomes [18,20,21].…”