Improvement In Depressive Symptoms Research Articles

An open trial of biofeedback for long COVID

ObjectiveBiofeedback is a therapeutic treatment model that teaches self-regulation of autonomic functions to alleviate stress-related symptoms. “Long COVID” refers to chronic physical and cognitive sequelae post-SARS-CoV-2 infection. This study examined the efficacy of a six-week intervention, consisting of weekly one-hour sessions combining heart rate variability and temperature biofeedback, for alleviating mood symptoms, somatic symptoms and sleep disturbance of patients diagnosed with long COVID. MethodsData were collected from 20 adult participants aged 22–63 (Mage = 44.1, SDage = 12.2) with varying long COVID symptoms. Within this single arm design, 16 of the 20 participants completed all six sessions of biofeedback; 14 completed an assessment at the three-month post-treatment time point. ResultsParticipants self-reported significant improvements in somatic, anxiety, and depressive symptoms, sleep quality, quality of life, and number of “bad days” immediately after the intervention and three months later (Cohen's d effect size (ES) = 1.09–0.46). Reduced number of medical doctor visits (ES = 0.85) and prescription drug use over the last month (odds ratio = 0.33), as well as improved emotional wellbeing (ES = 0.97) were observed at the three-month time point only. ConclusionResults suggest that this short, readily scalable intervention can be potentially efficacious in alleviating symptoms of long COVID. Despite notable improvements, the major limitation of this study is its lack of control group. While a randomized trial merits study, biofeedback appears to be a brief, effective, non-invasive, and low-cost treatment option for patients with chronic somatic symptoms secondary to SARS-CoV-2 infection.Clinicaltrials.govID: NCT05120648

A WHO digital intervention to address depression among young Chinese adults: a type 1 effectiveness-implementation randomized controlled trial

Common mental disorders among young people are rising globally. Current university-based interventions are inadequate to address the need for evidence-based interventions. We investigated the effectiveness and implementation of Step-by-Step (SbS), a WHO digital intervention to address depression, among Chinese university students with depressive symptoms. In this paper, we report a type 1 hybrid effectiveness-implementation randomized controlled trial conducted between September 2021 and September 2022. The control condition was enhanced treatment as usual (ETAU, psychoeducation). The primary outcome was improvement in depression symptoms. Secondary outcomes were improvements in psychological well-being, anxiety symptoms, and self-identified psychosocial problems. Effectiveness of the intervention was evaluated using generalized linear mixed models. Implementation outcomes were evaluated by thematic analysis of participant interviews. A total of 371 participants were enrolled to two treatment conditions in a 1:1 ratio. SbS resulted in a greater reduction in depressive symptoms at posttreatment (p = 0.004, Hedges’ g = 0.35), but no significant difference between SbS and ETAU was observed at three-month follow-up (p = 0.179, Hedges’ g = 0.16). The treatment effect was larger among those who adhered to the treatment (Hedges’ gs = 0.59 and 0.30). Subjective well-being also improved for SbS at both time points (Hedges’ gs = 0.31 and 0.30). In addition, SbS resulted in more improvement in anxiety symptoms at posttreatment (p = 0.029, Hedges’ g = 0.26), but not at three-month follow-up (p = 0.265, Hedges’ g = 0.13). The qualitative results demonstrated that the intervention was well-implemented as a self-help mental health service, with minimal support from peer supporters. In conclusion, Step-by-Step, a digital intervention developed by WHO, was effective in reducing depressive symptoms in the short term and improving psychological well-being in a longer term. The sustained effect on depression needs further investigation. Improving uptake and engagement in the program is needed for its scale-up implementation as a university-based mental health service for Chinese young adults. Trial registration: ChiCTR2100050214.

Action recommendations review in community-based therapy and depression and anxiety outcomes: a machine learning approach

BackgroundWhile the positive impact of homework completion on symptom alleviation is well-established, the pivotal role of therapists in reviewing these assignments has been under-investigated. This study examined therapists' practice of assigning and reviewing action recommendations in therapy sessions, and how it correlates with patients’ depression and anxiety outcomes.MethodsWe analyzed 2,444 therapy sessions from community-based behavioral health programs. Machine learning models and natural language processing techniques were deployed to discern action recommendations and their subsequent reviews. The extent of the review was quantified by measuring the proportion of session dialogues reviewing action recommendations, a metric we refer to as “review percentage”. Using Generalized Estimating Equations modeling, we evaluated the correlation between this metric and changes in clients' depression and anxiety scores.ResultsOur models achieved 76% precision in capturing action recommendations and 71.1% in reviewing them. Using these models, we found that therapists typically provided clients with one to eight action recommendations per session to engage in outside therapy. However, only half of the sessions included a review of previously assigned action recommendations. We identified a significant interaction between the initial depression score and the review percentage (p = 0.045). When adjusting for this relationship, the review percentage was positively and significantly associated with a reduction in depression score (p = 0.032). This suggests that more frequent review of action recommendations in therapy relates to greater improvement in depression symptoms. Further analyses highlighted this association for mild depression (p = 0.024), but not for anxiety or moderate to severe depression.ConclusionsAn observed positive association exists between therapists’ review of previous sessions’ action recommendations and improved treatment outcomes among clients with mild depression, highlighting the possible advantages of consistently revisiting therapeutic homework in real-world therapy settings. Results underscore the importance of developing effective strategies to help therapists maintain continuity between therapy sessions, potentially enhancing the impact of therapy.

Brief Interventions for Suicidal Youths in Medical Settings: A Meta-Analysis.

Most youths who die by suicide have interfaced with a medical system in the year preceding their death, placing outpatient medical settings on the front lines for identification, assessment, and intervention. Review and consolidate the available literature on suicide risk screening and brief intervention with youths in outpatient medical settings and examine common outcomes. The literature search looked at PubMed, OVID, CINAHL, ERIC, and PsychInfo databases. Interventions delivered in outpatient medical settings assessing and mitigating suicide risk for youths (ages 10-24). Designs included randomized controlled trials, prospective and retrospective cohort studies, and case studies. Authors extracted data on rates of referral to behavioral health services, initiation/adjustment of medication, follow-up in setting of assessment, suicidal ideation at follow-up, and suicide attempts and/or crisis services visited within 1 year of initial assessment. There was no significant difference in subsequent suicide attempts between intervention and control groups. Analysis on subsequent crisis service could not be performed due to lack of qualifying data. Key secondary findings were decreased immediate psychiatric hospitalizations and increased mental health service use, along with mild improvement in subsequent depressive symptoms. The review was limited by the small number of studies meeting inclusion criteria, as well as a heterogeneity of study designs and risk of bias across studies. Brief suicide interventions for youth in outpatient medical settings can increase identification of risk, increase access to behavioral health services, and for crisis interventions, can limit psychiatric hospitalizations.

Multifaceted Music Therapy for Depression in Dementia: A Network Meta-Analysis of Randomized Controlled Trials.

This study aimed to assess the efficacy of various music therapy interventions in ameliorating depressive symptoms in dementia patients, utilizing a network meta-analysis approach. We rigorously selected randomized controlled trials focused on music therapy for dementia with depressive symptoms from major electronic databases. The primary outcome measured was the impact on depressive symptoms, with the secondary outcome evaluating dropout rates across different intervention groups and standard care control groups. The research protocol has been duly registered with PROSPERO (Registration ID: CRD42023393059). Our network meta-analysis incorporated 14 randomized controlled trials involving a total of 1080 participants and examined a range of interventions, including active music therapy, listening to music, rhythmic music therapy, singing, and tailored music interventions. The analysis revealed that active music therapy combined with singing emerged as the most effective intervention, demonstrating a significant improvement in depressive symptoms in dementia patients (Standardized Mean Difference [SMD] = -0.89, 95% Confidence Interval [CI]: -1.48 to -0.30). In contrast, listening to music alone showed a smaller effect (SMD = -0.26, 95% CI: -0.71 to 0.20). This study was particularly noteworthy for not showing higher dropout rates compared to standard care, indicating its feasibility and acceptability in clinical settings. The findings of our study indicate that active music therapy combined with singing is an effective approach to reducing depressive symptoms in dementia patients, potentially due to enhanced social interaction. These results offer new perspectives for dementia care, suggesting a promising direction for further research and clinical application.

Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis.

Major depressive disorder (MDD) is associated with significant cognitive deficits during the acute and remitted stages. The aim of this systematic review and meta-analysis was to examine the course of cognitive function whilst considering demographic, treatment, or clinical features of MDD that could moderate the extent of cognitive change. Databases were searched to identify studies that reported on cognitive function in MDD with a ≥12-week test-retest interval. Relevant studies were pooled using random effects modelling to generate an inverse-variance, weighted, mean effect size estimate (Hedges' g) of cognitive change for each cognitive variable and for an overall composite cognitive domain. Of 6898 records, 99 eligible studies were identified from which 69 were meta-analysed, consisting of 4639 MDD patients (agemean = 40.25years, female% = 64.62%) across 44 cognitive variables. In over 95% of cognitive variables, improvements were either of non-significant, negligible, or of a small magnitude, and when compared to matched healthy controls, the possibility of practice effects could not be precluded. Depressive symptom improvement and the number of previous depressive episodes moderated the extent of cognitive change, demonstrating state- and scar-like features for one-quarter of the cognitive domains. Further longitudinal studies are required to elucidate the MDD cognitive trajectory from initial onset. Findings nonetheless suggest that following pharmacological and non-pharmacological treatment, cognitive change in MDD is typically small, but the capacity for change may be less with episode recurrence. Targeting cognition early in the course of illness may facilitate better prognosis and support a more complete functional recovery.

Correlation of Circadian Rhythms and Improvement of Depressive Symptoms in Acute Ischemic Stroke Patients.

To investigate the correlation between evening melatonin timing secretion, dim light melatonin onset (DLMO), and post-stroke depression (PSD) in acute ischemic stroke (AIS) patients and their influence on the improvement of depressive symptoms. 120 patients with a recent magnetic resonance imaging confirmed stroke were included. Salivary melatonin samples were collected at 5 time points within 1 week after hospitalization (7 p.m.-11 p.m., 1 sample per hour). The circadian phase was defined by calculating DLMO secretion. Post-stroke depressive symptoms were evaluated by the 17-item Hamilton Rating Scale for Depression (HRSD) both on day 7 of hospitalization and 3 months after stroke. Patients were divided into PSD and non-PSD groups based on whether the acute phase HRSD score was ≥8. Similarly, patients were divided into the improved depressive symptoms (IDS) and no improvement in depressive symptoms (non-IDS) groups based on whether the HRSD score at 3 months was lower than at baseline. Neurological recovery at 3 months was assessed using the modified Rankin Scale (mRS). The difference in DLMO between PSD and non-PSD patients was not statistically significant (p =0.173). In the non-IDS group, there was a significant decrease in melatonin secretion at 10 p.m. (p =0.012), and DLMO was significantly later than in the IDS group (p =0.017). Logistic regression analysis showed that DLMO (OR 1.91, 95%CI:1.13-3.23, p = 0.016) was an independent risk factor for persistent no improvement in depressive symptoms, which was associated with a markedly worse prognosis (p <0.001). Our findings suggest possible interventions for the very early identification of non- IDS patients.

Improvement of migraine depressive symptoms is not related to headache frequency: exploring the impact of anti-CGRP therapies.

The present study aimed to describe the prevalence and evolution of depressive symptoms in a cohort of migraine patients treated with anti-CGRP monoclonal antibodies. This is an exploratory, prospective, unicentric, one-year longitudinal study. We included migraine patients who started treatment with anti-CGRP monoclonal antibodies. Baseline demographic data, medical history, concomitant medication and migraine characteristics were collected. The presence of depressive symptoms was evaluated using the Beck Depression Inventory-II quarterly and treatment response was categorized according to the reduction in monthly headache days. A generalized mixed-effect regression model was used to model depression score over a one-year treatment taking into account frequency response rates. We included 577 patients: 84.2% females; median (range) age 47.0 (39.0-53.0)years, 46.1% (266/577) of them presented depressive symptoms at baseline (16.1% mild, 13.3% moderate and 16.6% severe). After six-month treatment, 47.4% (126/266) reduced headache frequency ≥50% after one year and 63.5% (169/266) achieved a clinically significant improvement in depression symptoms. We observed a 30.8% (-50.0%, -3.2%) main reduction in depression score during the first quarter. The improvement in depression symptoms was independently associated with headache frequency response: non-responders, -25.0% (-43.9%, -1.1%); partial responders, -30.2% (-51.3%, -7.6%); and good responders, -33.3% (-54.6%, -7.5%). Anti-CGRP monoclonal antibodies targeting CGRP are effective in reducing depressive symptoms in patients with migraine. The main change of depression score happens during the first threemonths of treatment. The reduction in depressive symptoms is independent of migraine frequency improvement.

Longitudinal Pain Outcomes Following an Intensive Pediatric Pain Rehabilitation Program: Testing Potential Treatment Mechanisms.

This study tested performance measures of physical functioning and pain-related psychosocial measures as potential mechanisms of improvements in outcomes following intensive outpatient interdisciplinary pain rehabilitation for adolescents. We hypothesized that improvements in performance measures of physical functioning, fear of pain, pain catastrophizing, and self-efficacy during treatment would be related to improvements in pain, functional disability, and depressive symptoms. Seventy-seven adolescents, 10 to 18 years old, completed self-report measures before treatment, after the first week, at discharge, and at the 3-month follow-up. Participants completed physical performance measures of physical and exercise capacity and core strength on day 1, after the first week, and at discharge. Linear mixed models were used to examine the association between changes in potential mechanisms and changes in outcomes, adjusting for age, sex, pain duration, and baseline functional disability. Statistically significant improvement in functional disability, pain, and depressive symptoms was demonstrated across the 4 time points. Improvements were also demonstrated in physical performance measures, fear of pain, pain catastrophizing, and self-efficacy. Improvements in pain catastrophizing predicted improvements in functional disability, pain, and depressive symptoms. Improvements in self-efficacy predicted improvements in all outcome variables except depression. Improvements in physical performance measures predicted improvements in some aspects of functional disability and pain, but not depressive symptoms. This study contributes to the growing literature on the effectiveness of pediatric intensive interdisciplinary pain rehabilitation programs and mechanisms that influence improvements in outcomes, an area that is currently underexplored. Results are important to guide future research and inform clinical practice.

Abstract TP87: Trending the Impact of Non-Body Weight Supported Treadmill Training on Physical Functioning and Depressive Symptoms in Chronic Stroke Survivors

Introduction: Stroke is the most common cause of adult-onset disability and is often associated with chronic limitations in activities of daily living (ADLs). Relatedly, the loss of functional independence has been suggested in increasing the likelihood of post-stroke depression, yet limited strategies are available to mitigate these risks. The objective of this secondary analysis study was to determine the immediate and residual impact of non- body weight supported treadmill training (NBWTT) on ADL and PHQ-9 in chronic stroke survivors. We hypothesized that training would result in improvement in ADL and depressive symptoms. Method: Data from 40-community-dwelling stroke survivors with mild-moderate walking impairment were used for this analysis. All participants underwent nine training sessions (3 per week x 3 weeks) of backward (BLTT/n=19) or forward (FLTT/n=21) NBWTT. The Stroke Impact Scale -16 (ADL-measure) and PHQ-9 (depression screen) were collected at baseline, post-training, at 30- and 90-day follow-up. Results: Both BLTT and FLTT resulted in an improvement in SIS-16 (p&lt;0.01) and PHQ9 &lt;0.01); however, there were no significant differences between groups. Post-training improvements in SIS and PHQ-9 were minimally inversely correlated (p&lt;0.01, R2=0.2). While the impact of training on SIS-16 and PHQ-9 were still present at 30 and 90-days post-training, these differences were no longer significant. Conclusion: Our preliminary findings suggest that NBWTT resulted transient improvements in both ADL and symptoms of depression. Future studies should investigate ways to extend the effects of training on these and similar quality of life measures.

Comparable Efficacy of Repeated Transcranial Direct Current Stimulation, Cognitive Behavioral Therapy, and Their Combination in Improvement of Cold and Hot Cognitive Functions and Amelioration of Depressive Symptoms.

This study aimed to evaluate the effectiveness of repeated transcranial direct current stimulation (rtDCS), cognitive behavioral therapy (CBT), and their combination (rtDCS-CBT) in the treatment of cognitive dysfunction, social cognition, and depressive symptoms in women diagnosed with major depressive disorder (MDD). A total of 40 female participants with MDD were randomly assigned to one of four groups: rtDCS, CBT, rtDCS-CBT, and a control group. The participants' depressive symptoms, executive functions, and social cognition were assessed at baseline, preintervention, postintervention, and during a 1-month follow-up. The rtDCS group received 10 sessions of anodal dorsolateral and cathodal ventromedial prefrontal cortex (2 mA for 20 minutes). The CBT group received 10 sessions of traditional CBT, whereas the combined group received CBT after the tDCS sessions. The results of the analysis of variance indicated that all intervention groups demonstrated significant improvements in depressive symptoms, cognitive dysfunction, and social cognition compared with the control group (all p < 0.001). Furthermore, the rtDCS-CBT group exhibited significantly greater reductions in depressive symptoms when compared with each intervention alone (all p < 0.001). Notably, working memory improvements were observed only in the rtDCS group ( p < 0.001). In conclusion, this study suggests that both CBT and tDCS, either individually or in combination, have a positive therapeutic impact on enhancing executive functions, theory of mind, and depressive symptoms in women with MDD.

Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression

BackgroundPatients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression.MethodsA total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26).ResultsLinear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009).ConclusionsOur results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males.Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn

Effectiveness of Shugan Jieyu capsules for psychiatric symptoms of epilepsy: a systematic review and meta-analysis

BackgroundThe relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy.MethodsWe searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events.ResultsNine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant.ConclusionsOur results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.

Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study.

There is growing evidence for the therapeutic effects of psychedelics. However, it is still uncertain how these drugs interact with serotonergic antidepressants (serotonin reuptake inhibitors (SRIs)). This study explores the interaction between psychedelics and SRIs in terms of therapeutic effects. The objective is to compare acute psychedelic effects and subsequent changes in well-being and depressive symptoms among 'SRI -' individuals (not on psychiatric medication) and 'SRI +' individuals (undergoing SRI treatment). Using prospective survey data, the study employs multivariate analysis of covariance (MANCOVA) and linear mixed effect models to analyse subjective differences and changes in well-being and depressive symptoms pre- and post-psychedelic experiences. Results indicate that 'SRI -' participants experience significantly more intense subjective effects compared to 'SRI +' participants (F = 3.200, p = 0.016) in MANCOVA analysis. Further analysis reveals 'SRI -' individuals report stronger mystical (18.2% higher, p = 0.048), challenging (50.9% higher, p = 0.001) and emotional breakthrough experiences (31.9% higher, p = 0.02) than 'SRI +' individuals. No differences are observed in drug-induced visual effects (p = 0.19). Both groups exhibited similar improvements in well-being and depressive symptoms after the psychedelic experience. Individuals presumed to be on serotonergic antidepressants during psychedelic use display reduced subjective effects but similar antidepressant effects compared to those not undergoing SRI treatment. Further controlled research is needed to comprehend the interplay between serotonergic antidepressants and psychedelics, illuminating potential therapeutic benefits and limitations in clinical contexts.

Switching to Vortioxetine in Patients with Poorly Tolerated Antidepressant-Related Sexual Dysfunction in Clinical Practice: A 3-Month Prospective Real-Life Study.

To determine the effectiveness of switching to vortioxetine due to SD in a routine clinical practice setting. observational pragmatic and naturalistic study to determine the effectiveness of the switch to vortioxetine (mean dosage 13.11 ± 4.03) in 74 patients aged 43.1 ± 12.65 (54% males) at risk of discontinuing treatment due to sexual dysfunction. The PRSexDQ*- SALSEX scale (* Psychotropic-Related Sexual Dysfunction Questionnaire) was applied at two moments: baseline visit and after 3 months of follow-up. global Sexual Dysfunction (SD) measured with the SALSEX scale decreased significantly between the baseline visit (10.32; SD 2.73) and the follow-up visit (3.78; SD 3.68), p < 0.001. There was a significant improvement (p < 0.001) at the endpoint including decreased libido, delay of orgasm, anorgasmia and arousal difficulties in both sexes. After switching to vortioxetine, 83.81% of patients experienced an improvement in sexual function (43.2% felt greatly improved). Most patients (83.3%) who switched to vortioxetine continued treatment after the follow-up visit. A total of 58.1% of patients showed an improvement in depressive symptoms from the baseline visit. switching to vortioxetine is an effective and reliable strategy to treat patients with poorly tolerated previous antidepressant-related sexual dysfunction in real-life clinical settings.

Ketamine for Adults With Treatment-Resistant Depression or Posttraumatic Stress Disorder: A 2023 Update

What Is the Issue?&#x0D; &#x0D; Many drug treatments are available for depression, but 22% of people in Canada with the condition have treatment-resistant depression (TRD). For people with TRD, standard drug treatments do not improve their symptoms or do not work for long, and their depression persists.&#x0D; Posttraumatic stress disorder (PTSD) is a disabling mental health condition that affects about 9% of people in Canada in their lifetime. Few drugs are available for treating PTSD, none of which are considered effective.&#x0D; Ketamine is a hallucinogenic drug used primarily for anesthesia. Ketamine has also been explored for other indications, such as TRD and PTSD, generating questions about whether it could be a treatment option for these conditions.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; We conducted a review of the clinical effectiveness, cost-effectiveness, and evidence-based guidelines on the use of ketamine in adults with TRD or PTSD, to help guide decisions on the use of ketamine for managing these conditions.&#x0D; An information specialist conducted a search of peer-reviewed and grey literature sources published in March 2022 or later. One reviewer screened citations and selected and critically appraised the included studies.&#x0D; CADTH engaged a patient with lived experience of TRD who shared their experiences and perspectives on ketamine-assisted psychotherapy. These perspectives helped us to contextualize the literature and appreciate nuances of the experience.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; Ketamine could lead to an immediate improvement in depressive symptoms and suicidal ideation compared to placebo or midazolam in adults with TRD. The longest follow-up was 90 days, and the longest lasting effect after a dose was 28 days. Serious side effects of ketamine — such as dissociation — were rare and short-lived, lasting hours, in adults with TRD.&#x0D; It is uncertain if ketamine is an effective and safe treatment for symptoms of PTSD, due to little to no evidence suggesting its effectiveness or safety against placebo, midazolam, or opioids.&#x0D; Most studies evaluated ketamine given intravenously, and we found limited evidence on intramuscular (IM), subcutaneous, and intranasal routes of administration. We found no studies on oral or sublingual administration of ketamine and no studies comparing the different ways that ketamine can be given for TRD or PTSD.&#x0D; An economic evaluation found that IV ketamine was likely to be cost-effective compared to intranasal esketamine in adults with TRD from a health care perspective in the US. However, from a patient perspective, IV ketamine was unlikely to be cost-effective compared to esketamine, due to comparable levels of clinical effectiveness and lower costs of esketamine attributable to commercial insurance coverage and manufacturer assistance programs.&#x0D; A US guideline on TRD suggests ketamine as augmentation to antidepressants. A US guideline on PTSD does not suggest the use of ketamine as therapy.&#x0D; The patient contributor CADTH engaged for this review highlighted the benefits, stigma, and barriers of ketamine therapy, including financial implications.&#x0D; &#x0D; What Does This Mean?&#x0D; &#x0D; There is some clinical effectiveness and cost-effectiveness evidence and a guideline recommendation to support the short-term use of ketamine in adults with TRD.&#x0D; Clinical effectiveness evidence and a guideline recommendation do not support the use of ketamine in adults with PTSD.&#x0D; Future research is necessary to understand the effectiveness and safety of ketamine as therapy for TRD in larger populations over longer periods and for PTSD for any follow-up duration.&#x0D; Decision-makers should consider offering ketamine in an equitable manner.&#x0D;

Long-term quality of life after repeated ketamine infusions in anxious and nonanxious patients with depression

BackgroundThere have been many studies on the benefits of repeated ketamine infusions on patients' depression but few on the impact of ketamine on patients' long-term quality of life (QoL). This study investigated long-term QoL in individuals with depression, both anxious and nonanxious. MethodsA total of 107 individuals with a diagnosis of depression were included in the study. The patients were evaluated on Days 0, 13 and 26 and Months 6 and 9, and they received six ketamine infusions over the course of two weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale and the Patient Health Questionnaire-9 (PHQ-9) Scale were used to measure depressive symptoms and QoL. Linear mixed models were used to evaluate depressive symptoms and QoL during ketamine treatment. ResultsA total of 67.2 % of patients were diagnosed with anxious depression. In the long term, there were no significant differences in the time-by-group interactions for general QoL (F = 0.510; P = 0.676), physical QoL (F = 2.092; P = 0.102), psychological QoL (F = 0.102; P = 0.959), social QoL (F = 2.180; P = 0.091), or environmental QoL (F = 1.849; P = 0.139) between the two groups. LimitationsThe main limitation of this study is its open-label design. ConclusionThe improvement in depression symptoms and QoL following ketamine treatment was not impacted by the presence or absence of anxiety in patients who were depressed prior to treatment. Only occasionally did depressed individuals with anxiety experience a worsening of their quality of life compared to those without anxiety.

Exercise alters molecular rhythms in the central nervous system that negatively correlate with depression-like behavior.

Major depressive disorder (MDD) ranks among the top 10 leading causes of death. However, exercise is known to improve depressive symptoms but the mechanism responsible is still unknown. To date, numerous studies have shown that molecular rhythms and exercise are associated with MDD. Thus, we hypothesized that exercise could affect the expression of central nervous system clock genes to improve depressive symptoms. Ninety adult male Sprague-Dawley rats (250 g) were divided into a control Normal Group, an unpredictable chronic mild stress (CMS) treated CMS Group and an Exercise Group, which was intervened by a moderate-intensity exercise training on a treadmill at 2 p.m. every day for 4 weeks after CMS treatment. The open field test, elevated plus maze and forced swim test were employed to test mood-related behaviors. The telemetry recording method recorded voluntary locomotor activity and core body temperature. Expression of core clock genes in the suprachiasmatic nucleus (SCN) was tested by qRT-PCR. Compared with the CMS Group, depressive symptoms were improved in the Exercise Group ( P < 0.05). Moreover, the periodic changes of molecular rhythms in the Exercise Group were close to those of rats in Normal Group. Next, exercise increased oscillations of expression of core clock genes in SCN after CMS treatment, and the amplitudes of core clock gene expression oscillations were negatively correlated with depressive-like behavior. Our findings suggested that exercise could change the expressions of central clock genes in MDD animals, and this effect was positively correlated with the improvement of depressive symptoms by exercise.

Targeting metaplasticity mechanisms to promote sustained antidepressant actions.

The discovery that subanesthetic doses of (R, S)-ketamine (ketamine) and (S)-ketamine (esketamine) rapidly induce antidepressant effects and promote sustained actions following drug clearance in depressed patients who are treatment-resistant to other therapies has resulted in a paradigm shift in the conceptualization of how rapidly and effectively depression can be treated. Consequently, the mechanism(s) that next generation antidepressants may engage to improve pathophysiology and resultant symptomology are being reconceptualized. Impaired excitatory glutamatergic synapses in mood-regulating circuits are likely a substantial contributor to the pathophysiology of depression. Metaplasticity is the process of regulating future capacity for plasticity by priming neurons with a stimulation that alters later neuronal plasticity responses. Accordingly, the development of treatment modalities that specifically modulate the duration, direction, or magnitude of glutamatergic synaptic plasticity events such as long-term potentiation (LTP), defined here as metaplastogens, may be an effective approach to reverse the pathophysiology underlying depression and improve depression symptoms. We review evidence that the initiating mechanisms of pharmacologically diverse rapid-acting antidepressants (i.e., ketamine mimetics) converge on consistent downstream molecular mediators that facilitate the expression/maintenance of increased synaptic strength and resultant persisting antidepressant effects. Specifically, while the initiating mechanisms of these therapies may differ (e.g., cell type-specificity, N-methyl-D-aspartate receptor (NMDAR)subtype-selective inhibition vs activation, metabotropic glutamate receptor 2/3 antagonism, AMPA receptor potentiation, 5-HT receptor-activating psychedelics, etc.), the sustained therapeutic mechanisms of putative rapid-acting antidepressants will be mediated, in part, by metaplastic effects that converge on consistent molecular mediators to enhance excitatory neurotransmission and altered capacity for synaptic plasticity. We conclude that the convergence of these therapeutic mechanisms provides the opportunity for metaplasticity processes to be harnessed as a druggable plasticity mechanism by next-generation therapeutics. Further, targeting metaplastic mechanisms presents therapeutic advantages including decreased dosing frequency and associated diminished adverse responses by eliminating the requirement for the drug to be continuously present.

Effectiveness of two systems-level interventions to address perinatal depression in obstetric settings (PRISM): an active-controlled cluster-randomised trial

Perinatal depression is a common and undertreated condition, with potential deleterious effects on maternal, obstetric, infant, and child outcomes. We aimed to compare the effectiveness of two systems-level interventions in the obstetric setting-the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms and the PRogram In Support of Moms (PRISM)-in improving depression symptoms and participation in mental health treatment among women with perinatal depression. In this cluster-randomised, active-controlled trial, obstetric practices across Massachusetts (USA) were allocated (1:1) via covariate adaptive randomisation to either continue participating in the MCPAP for Moms intervention, a state-wide, population-based programme, or to participate in the PRISM intervention, which involved MCPAP for Moms plus a proactive, multifaceted, obstetric practice-level intervention with intensive implementation support. English-speaking women (aged ≥18 years) who screened positive for depression (Edinburgh Postnatal Depression Scale [EPDS] score ≥10) were recruited from the practices. Patients were followed up at 4-25 weeks of gestation, 32-40 weeks of gestation, 0-3 months postpartum, 5-7 months postpartum, and 11-13 months postpartum via telephone interview. Participants were masked to the intervention; investigators were not masked. The primary outcome was change in depression symptoms (EPDS score) between baseline assessment and 11-13 months postpartum. Analysis was done by intention to treat, fitting generalised linear mixed models adjusting for age, insurance status, education, and race, and accounting for clustering of patients within practices. This trial is registered with ClinicalTrials.gov, NCT02760004. Between July 29, 2015, and Sept 20, 2021, ten obstetric practices were recruited and retained; five (50%) practices were randomly allocated to MCPAP for Moms and five (50%) to PRISM. 1265 participants were assessed for eligibility and 312 (24·7%) were recruited, of whom 162 (51·9%) were enrolled in MCPAP for Moms practices and 150 (48·1%) in PRISM practices. Comparing baseline to 11-13 months postpartum, EPDS scores decreased by 4·2 (SD 5·2; p<0·0001) among participants in MCPAP for Moms practices and by 4·3 (SD 4.5; p<0·0001) among those in PRISM practices (estimated difference between groups 0·1 [95% CI -1·2 to 1·4]; p=0·87). Both the MCPAP for Moms and PRISM interventions were equally effective in improving depression symptoms. This finding is important because the 4-point decrease in EPDS score is clinically significant, and MCPAP for Moms has a lower intensity and greater population-based reach than does PRISM. US Centers for Disease Control and Prevention.