Subjective and Objective Measures of Cognitive Function are Correlated in Persons with Post-COVID-19 Condition: A Secondary Analysis of a Randomized Controlled Trial.

Background: It remains unclear whether subjective and objective measures of cognitive function in Post COVID-19 Condition (PCC) are correlated. The extent of correlation has mechanistic and clinical implications. Methods: This post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial contains baseline data of subjective and objective measures of cognition in a rigorously characterized cohort living with PCC. Herein, we evaluated the association between subjective and objective condition function, as measured by the Perceived Deficits Questionnaire, 20-item (PDQ-20) and the Digit Symbol Substitution Test (DSST) and Trails Making Test (TMT)-A/B, respectively. Results: A total of 152 participants comprised the baseline sample. Due to missing data, our statistical analyses included 150 for self-reported PDQ-20, 147 individuals for combined DSST-measured cognitive function (composite z-score of the Pen/Paper plus Online CogState Version, N combinedDSST ), 71 for in-person DSST-measured cognitive function (Pen/Paper Version), 70 for TMT-A-measured cognitive function, and 70 for TMT-B-measured cognitive function. After adjusting for age, sex, and education, PDQ-20 was significantly correlated with pen-and-paper DSST (ß = -0.003, p = 0.002) and TMT-B (ß = 0.003, p = 0.008) scores, but not with TMT-A scores (ß = -0.001, p = 0.751). Conclusions: Overall, a statistically significant correlation was observed between subjective and objective cognitive functions. Clinicians providing care for individuals with PCC who have subjective cognitive function complaints may consider taking a measurement-based approach to cognition at the point of care that focuses exclusively on patient-reported measures.

Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder.

Borderline personality disorder (BPD) has high rates of comorbidity with mood disorders, including treatment-resistant depression (TRD). Comorbidity of BPD with depression is associated with poorer response to antidepressants. Intravenous ketamine is a novel treatment for TRD that has not been specifically evaluated in patients with comorbid BPD. In this retrospective analysis of data collected from participants who received care at the Canadian Rapid Treatment Centre of Excellence (CRTCE; Braxia Health; ClinicalTrials.gov: NCT04209296), we evaluated the effectiveness of intravenous ketamine in a TRD population with comorbid BPD (N=100; n=50 BPD-positive compared with n=50 BPD-negative). Participants were administered four doses of intravenous ketamine (0.5-0.75mg/kg over 40 minutes) over two weeks. The primary outcome measures were changes in depressive symptom severity (as measured by Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR16)) and borderline symptom severity (as measured by Borderline Symptom List 23-item (BSL-23)). Both BPD-positive and BPD-negative groups improved significantly on the QIDS-SR16, QIDS-SR16 suicide ideation item, anxiety, and functionality scales with large effect sizes. There was no significant difference between groups. The BPD-positive group exhibited significant reduction of 0.64 on BSL-23 scores and a significant reduction of 5.95 on QIDS-SR16 scores. Patients with TRD and comorbid BPD receiving ketamine exhibited a significant reduction in symptoms of depression, borderline personality, suicidality, and anxiety.

Olanzapine and samidorphan combination treatment: A systematic review.

INTRODUCTION: The overarching aim of this review is to synthesize the efficacy, tolerability, and weight-mitigation effects of the olanzapine/samidorphan (OLZ/SAM) combination treatment in adults with schizophrenia and bipolar disorder-I. METHODS: A systematic search of PubMed, Web of Science, Embase, and The Cochrane Library was conducted on August 15th, 2021. Studies were included if they investigated the use of OLZ/SAM treatment in patients with schizophrenia or bipolar disorder-I, and reported the clinical outcomes: efficacy, change in weight or waist circumference, tolerability, pharmacokinetics, or change in metabolic parameters. A narrative synthesis was undertaken of the data. RESULTS: Eight studies met the inclusion criteria. All identified studies were conducted in adults with schizophrenia. Compared to OLZ-monotherapy, OLZ/SAM was associated with decreased odds of developing clinically significant (>10%) weight gain (OR=0.50, 95% CI:0.31,0.80; p= 0.003) and increase in waist circumference (risk difference = -17.1% 95% CI:-26.3,-7.8) from baseline measurements respectively. In another study, OLZ was 2.7 times more associated with clinically significant weight gain as compared to OLZ/SAM (OR=2.73, 95% CI:1.11, 6.67; p = 0.023). The clinical efficacy of OLZ/SAM remained similar to OLZ with improved tolerability in both short- and long-term studies with no significantly altered pharmacokinetic properties of the constituent agents. CONCLUSION: OLZ/SAM-treatment is associated with mitigated weight-gain liability when compared to OLZ-monotherapy in adults with schizophrenia. Additional studies are needed to ascertain patient acceptability, appropriate selection and sequencing of OLZ/SAM in the treatment algorithms for adults with schizophrenia (and BD-I), as well as to determine cost-effectiveness and long-term metabolic effects.

Ketamine use in pediatric depression: A systematic review.

Pediatric depression is a common psychiatric disorder that is associated with significant morbidity and mortality. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with demonstrated antidepressant effects in the adult population, however, the efficacy and safety of ketamine for the treatment of pediatric depression remains poorly understood. Electronic databases were searched from inception to June 2022 to identify relevant articles. Six articles involving 46 participants with a mean age of 15.7 years were included in this systematic review. Out of six articles, three were case reports, one was a randomized clinical trial (RCT) and two were open-label trials. All studies used 0.5 mg/kg intravenous ketamine except for one, which used 2-7 micrograms/kg. Ketamine was significantly associated with reduced depressive symptoms without severe adverse events. Taken together, the results of these studies demonstrated the potential role of ketamine for treating pediatric depression. Several important limitations were identified, most notably the small sample sizes of the component studies, and that all studies administered intravenous ketamine. Further studies with larger sample sizes and different administration modalities are needed to better determine the efficacy and safety of ketamine in pediatric depression.