Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study.

BACKGROUND: Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and/or IN routes. METHODS: In this context, we conducted an open-label clinical trial for investigating the efficacy and safety of 8 weekly sessions of SC esketamine in TRD patients (n = 30). RESULTS: At the end of the treatment, a partial response rate of 26.09 %, a response rate of 52.17 % and remission rate of 34.78 % were observed, assessed by Montgomery-Åsberg Depression Rating Scale. Moreover, the self-reported depressive symptoms, as measured by the Beck Depression Inventory II (BDI-II), significantly decreased from the baseline to the final session, and the improvements were sustained throughout the week. Follow-up evaluations (BDI-II) up to the sixth month consistently showed scores lower than the baseline. LIMITATIONS: The small sample size and the drop-out during the follow-up phase may limit the generalizability of the findings. Additionally, the absence of a control group necessitates cautious interpretation of causality. CONCLUSIONS: This groundbreaking study, which addresses SC esketamine treatment for TRD, reported promising response and remission rates, as well as sustained antidepressant effects. It highlights the need for further research to improve and expand our knowledge of this innovative, more accessible, and cost-effective therapeutic approach.

Effectiveness of an affect-adjusted, supervised, multimodal, online and home-based exercise group protocol for major depression: A randomized controlled trial.

This randomized controlled trial investigated the effectiveness of an affect-adjusted, supervised, multimodal, online, and home-based exercise group protocol as an adjunct therapy to antidepressants on depressive symptoms, cardiorespiratory fitness, and side effects related to antidepressants in adults with major depression (MDD, diagnosed by a clinician). Depressive symptom scales were administered by a psychiatrist and self-reported. A health-related measure (i.e., cardiorespiratory fitness), was also administered. The exercise intervention was adjusted by perceived effort and affect (pleasure and enjoyment) toward exercise and lasted 12 weeks. In total, 59 adults with MDD were divided into two groups: the exercise-group (EG; exercise + pharmacotherapy) with 26-patients (76.9 % females, mean age 28.5 years) and the control-group (CG, pharmacotherapy) with 33-patients (78.7 % females, mean age 25.6 years). The EG had a lower dropout rate (15.3 %) than CG and an increase in cardiorespiratory fitness (CRF), which was not observed in the CG. Both groups showed a decrease in self-reported depressive symptoms. However, the EG had significantly lower depressive symptom scores at t1 and t2. The EG also had higher remission rates (t1, EG: = 42.3 % and CG = 27.2 %) and remission rates (t2, EG: = 72.7 % and CG = 48.1 %) than CG, which were maintained during the four month follow-up. Side effects from anti-depressant medication were larger in the EG compared to CG. Complementing usual care for MDD with exercise resulted in better clinical outcomes and supports the use of this type of exercise protocol in the clinical management of depression.

Rapid and long-lasting effects of subcutaneous esketamine on suicidality: An open-label study in patients with treatment-resistant depression.

Therapeutics for suicide management is limited, taking weeks to work. This open-label clinical trial with 18 treatment-resistant depressive patients tested subcutaneous esketamine (8 weekly sessions) for suicidality. We noted a rapid and enduring effect of subcutaneous esketamine, lasting from one week to six months post-treatment, assessed by the Beck Inventory for Suicidality (BSI). There was an immediate drop in suicidality, 24 h following the initial dose, which persisted for seven days throughout the eight-week dosing period. Additionally, this study is the first to examine a six-month follow-up after multiple administrations of subcutaneous esketamine, finding consistently lower levels of suicidality throughout this duration. Conversely, suicidality also was measured along the 8-weeks of treatment by a psychiatrist using the Montgomery-Asberg Depression Rating Scale (MADRS), which showed significant reduction only after two treatment sessions expanding until the last session. Moreover, notably, 61% of patients achieved remission on suicidality (MADRS). These results suggest that weekly subcutaneous esketamine injections offer a cost-effective approach that induces a rapid and sustained response to anti-suicide treatment. This sets the stage for further, more controlled studies to corroborate our initial observations regarding the effects of SC esketamine on suicidality. Registered trial at: https://ensaiosclinicos.gov.br/rg/RBR-1072m6nv.

Self-Reported Mood and Lifestyle-Related Physical Activity of Young Adults With Major Depressive Disorder.

We investigated whether mood and lifestyle-related indicators of physical health are differentially expressed according to self-reported levels of depressive symptoms among young adults with a current episode of major depression. In a cross-sectional study, we recruited 94 young adults (females = 67, 71.3%; males = 27, 28.7%; aged 18-35 years) with a current episode of major depression. We assessed their mood with the Profile of Mood States (POMS), and Beck Anxiety Inventory-(BAI), sleep with the Pittsburgh Sleep Quality Index (PSQI), physical activity with the Simple Physical Activity Questionnaire (SIMPAQ), and their cardiorespiratory fitness. Participants' depression levels were classified as follows using established cut-points: (a) Mild Depressive Symptoms (MIDS, BDI-II 14-19 points, n = 17), (b) Moderate Depressive Symptoms (MODS, BDI-II 20-28 points, n = 37) or (c) Severe Depressive Symptoms (SEDS, BDI-II 29-63 points, n = 40). As expected, we found that young adults with SEDS, when compared to those with MODS and MIDS, showed higher depressive mood on the POMS, and they exhibited greater anxiety symptoms, lower reported 'vigor' on physical activity measures, worse sleep quality as expressed by their global score sleep; daytime dysfunction; and sleep disturbance, and they showed lower cardiorespiratory fitness. Those with moderate depressive symptoms only differed from those with mild symptoms with respect to hostility, fatigue and mood disturbance. Although there was a gradient whereby worse mental and physical health indicators were more closely related to the SEDS depression categorization, while healthier indicators were associated with the MIDS category, some parameters were not different between the MDD severity groups, particularly when comparing MIDS and MODS. Clinicians treating patients with MDD should consider these factors when designing lifestyle-based interventions.

Effects of exercise on cognitive functioning in adults with serious mental illness: A meta analytic review.

Cognitive performance is usually impaired in those with serious mental illness (SMI). Exercise may improve cognitive functioning, but studies examining the effects of exercise in SMI indicate heterogenous findings. To estimate the effects of exercise on cognitive outcomes in people with SMI. Randomized controlled trials evaluating the acute or chronic effects of exercise on cognitive functioning in SMI were searched from inception to December 26th, 2022 on major electronic databases. Random effect meta-analyses were conducted to assess the effects of exercise on over the cognitive domains and Standardized Mean Differences (SMD) and 95% confidence intervals (CIs) were used as the effect size measure. Funnel plots and Egger's test of effect size and the Trim and Fill procedure applied if evidence of publication bias was noted. Methodological quality was assessed using RoB 2. A total of 15 chronic (1 acute), 936 participants (46.7% women). Exercise showed large effects on reasoning and problem solving; small effects on executive functioning. Per diagnosis, exercise showed moderate positive effects on executive functioning and large effects on processing speed in people with depression; large effects on reasoning and problem solving in people with schizophrenia. The present study indicates a large beneficial effect of chronic physical exercise on reasoning and problem solving and small effects on executive functioning in people with SMI.

Moderators of ayahuasca's biological antidepressant action.

Introduction: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). Methods: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72). Results: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. Discussion: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

Analysis of stress tolerance, competitive-anxiety, heart rate variability and salivary cortisol during successive matches in male futsal players.

BACKGROUND: This study aimed to compare the stress tolerance, competitive anxiety, heart rate variability and salivary cortisol before and during successive futsal competitive matches (3 matches in 4 days) in young male futsal players. METHODS: 10 young male futsal players (16.9 ± 0.7 age; 71.0 ± 5.1 kg; 174.9 ± 4.3 cm) were monitored during one training session and across a competitive period with 3 successive matches. External load was determined by the PlayerLoad method, while session rating of perceived exertion was used to calculate the internal training and competitive load. The stress tolerance was examined using Daily Analysis of Life Demand in Athletes questionnaire and the Competitive State Anxiety Inventory was used to analyze the competitive anxiety. The Time and frequency monitoring parameters were used to analyze the vagal cardiac autonomic marker. sC was analyzed using enzyme-linked immunosorbent assay. RESULTS: A generalized estimating equation showed a significant difference for PlayerLoad from M1 to TS, M2 and M3, from M2 to M3 (p < 0.05), and for session rating of perceived exertion from M1 to Ts and M3 (p < 0.05). A difference for sources [χ2 (3) = 1.481, p = 0.68] or symptoms [χ2 (3) = 3.893, p = 0.27] was not found. There was no significant difference in any of the competitive anxiety [cognitive anxiety (F (1.644; 14.799) = 4.6, p = 0.73, ŋ2 p = 0.28), somatic anxiety (F (2,09; 18,85) = 26.07 p = 0.057; ŋ2p = 0.27) or self-confidence (F(2.07; 18.85) = 15.875 p = 0.152; ŋ2p = 0.18)] domains. The HRV parameters (time domain and frequency) and Salivary Cortisol (sC) (χ2 (3) = 4.320 p = 0.229) did not significantly change during the successive matches. CONCLUSION: The competitive scenario in which the players were evaluated did not significantly modify the stress tolerance, or the athletes' state of anxiety, which in turn was not able to promote changes in the cardiac vagal modulation or in the sC levels before the matches.

Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior.

Observational studies of long-term users of ayahuasca, an Amazonian psychedelic brew, suggest an increase in resilience via improvements in emotion and cognition. Ayahuasca has also demonstrated clinical antidepressant effects in human and animal studies; however, its potential prophylactic action in depression has not been previously studied. Therefore, this experimental study sought to evaluate the potential prophylactic effects of repeated and long-term ayahuasca use, via the modulation of resilience, in a non-human primate animal model, Callithrix jacchus, subjected to a protocol for induction of depressive-like behavior. For the formation of the study groups, some juvenile marmosets were kept in their family groups (GF = 7), while for the two experimental groups, the animals were removed from the family and kept socially isolated. Then, part of the isolated animals made up the group in which ayahuasca was administered (AG, n = 6), while for others, no intervention was made (IG, n = 5). AG animals took ayahuasca (1.67 mL/300g body weight) at weeks 4 (before isolation), 8, and 12 (during isolation) of the study. More adaptive stress response was observed for the AG when compared to the IG. The AG showed higher cortisol reactivity and fecal cortisol levels than IG, while both measures were similar to FG. Moreover, AG animals showed no signs of anhedonia and no increase in chronic stress-related behaviors, which were expressed by the IG. Thus, ayahuasca seems to promote the expression of resilient responses, indicating a prophylactic action, buffering the emergence of depressive-like behaviors and cortisol alterations associated with major depression. These results are encouraging for further research on the prophylactic use of psychedelics to prevent psychopathologies associated with chronic stress.

A Congested Match Schedule Alters Internal Match Load and Affects Salivary Immunoglobulin A Concentration in Youth Soccer Players.

ABSTRACT: Mortatti, AL, Oliveira, RSCd, Pinto, JCBdL, Galvão-Coelho, NL, Almeida, RN, Aoki, MS, and Moreira, A. A congested match schedule alters internal match load and affects salivary immunoglobulin A concentration in youth soccer players. J Strength Cond Res 36(6): 1655-1659, 2022-The aim of this study was to analyze the effects of a congested match schedule (CMS) undertaken after a tapering week, on internal match load (IML) and salivary immunoglobulin A (SIgA) concentration in 12 youth soccer players (16.6 ± 0.5 years; 175 ± 8 cm; 65 ± 8 kg) who performed 4 official matches within a 4-day period. Internal match load was determined using the session-rating of perceived exertion method and the competitive strain (CS) and monotony index (MI) were also determined. Saliva sampling was conducted, before the last training day of a tapering week (training) preceding the CMS, 60 minutes before the first match (match-1), and 22 hours after match 4 (postmatch 4). Salivary immunoglobulin A was analyzed by ELISA. The results of the analysis of variance with repeated measures showed a significant difference for IML across the matches (p < 0.001). A significant reduction in SIgA was observed from prematch 1 to postmatch 4 (p = 0.019). Regarding the change in SIgA (ΔSIgA), 58.3% of the players presented values equal/higher than the minimal detectable change. A large within-individual correlation was observed between ΔSIgA and MI and CS (r = 0.71 and r = 0.72: p < 0.01, respectively). The current findings suggest that youth players participating in a CMS may present a decrease in mucosal immunity function. In addition, data suggest that the MI and CS may be used as valuable markers for monitoring competition load during CMS in youth soccer players.

Ayahuasca for the Treatment of Depression.

Ayahuasca, the vine of the souls in Quechua, is a psychedelic brew with a few formulations that most often include the bark of a liana in the Malpighiaceae family (Banisteriopsis caapi), with leaves from a shrub in the coffee family Rubiaceae (Psychotria viridis). Mixed with water and boiled for hours or days, it produces a brownish-colored liquid with a strong and characteristic taste. Ayahuasca contains the psychedelic tryptamine N,N-Dimethyltryptamine (DMT), and Monoamine Oxidase Inhibitors (MAOi), and in the past few years, it has been tested. In recent years its antidepressant properties have been put to the test. Evidence from open and randomized placebo-controlled clinical trials has shown encouraging results, indicating significant and rapid antidepressant effects, starting as early as 1 day after the ayahuasca intervention. In addition, we have explored the nature of these effects using multivariate measures. In this article, we will review the history, pharmacology, clinical trials, and clinical and behavioral markers associated with the antidepressant effects of ayahuasca.