Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

BACKGROUND: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period. METHODS: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466). FINDINGS: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline. CONCLUSIONS: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity. FUNDING: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.

The effect of lifestyle interventions on depressive symptom severity in individuals with type-2 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a severe metabolic condition which is commonly comorbid with depression. Lifestyle factors are involved in the pathophysiology of both conditions; however, the role of lifestyle interventions remains unclear. OBJECTIVE: The objective of this study is to systematically review the literature on randomized controlled trials evaluating the effect of lifestyle interventions on depressive scores in patients with T2DM. METHODS: A systematic search was conducted in computerized databases before October 2022. A random-effects model was used to investigate the effect of lifestyle interventions on depression scores and meta-regression was conducted to assess the influence of age and disease onset. RESULTS: Six trials met the eligibility criteria for inclusion. A statistically significant reduction in depression scores was found for groups receiving lifestyle interventions compared to controls (SMD = -0.49 [95%CI -0.89 to -0.08]; p = 0.0269]). Interventions increased in efficacy with the age of the participants but no significant correlation was found with years since disease onset. Participants in a control group receiving a less intense lifestyle intervention demonstrated improved depression scores when compared to those who received standard care or no intervention at all. Trial design and outcome measurement tools were heterogeneous between studies and limited data on antidepressant use was available which may introduce bias into the results. CONCLUSION: Lifestyle interventions were effective at improving depressive symptom severity in patients with T2DM.

Does the Ranking Matter? A Retrospective Cohort Study Investigating the Impact of the 2018 CANMAT and ISBD Guidelines for the Management of Patients with Bipolar Disorder Treatment Recommendations for Acute Mania on Rehospitalization Rates.

OBJECTIVE: There is limited data about the impact of mood disorders treatment guidelines on clinical outcomes. The objective of this study was to investigate the impact of prescribers' adherence to the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) treatment guidelines recommendations on the readmission rates of patients hospitalized for mania. METHOD: A retrospective cohort of all individuals admitted due to acute mania to Kingston General Hospital, Kingston, ON, from January 2018 to July 2021 was included in this study. Patient variables and data regarding index admission and subsequent hospitalizations were extracted from medical records up to December 31, 2021. Treatment regimens were classified as first-line, second-line, noncompliant, or no treatment. We explored the associations between treatment regimens and the risk of readmissions using univariate, multivariate, and survival analysis. RESULTS: We identified 211 hospitalizations related to 165 patients. The mean time-to-readmission was 211.8 days (standard deviation [SD] = 247.1); the 30-day rehospitalization rate was 13.7%, and any rehospitalization rate was 40.3%. Compared to no treatment, only first-line treatments were associated with a statistically significant decreased risk of 30-day readmission (odds ratio [OR] = 0.209; 95% CI, 0.058 to 0.670). The risk of any readmission was reduced by first-line (OR = 0.387; 95% CI, 0.173 to 0.848) and noncompliant regimens (OR = 0.414; 95% CI, 0.174 to 0.982) compared to no treatment. On survival analysis, no treatment group was associated with shorter time-to-readmission (log-rank test, p = 0.014) and increased risk of readmission (hazard ratio = 2.27; 95% CI, 1.30 to 3.96) when compared to first-line medications. CONCLUSIONS: Treatment with first-line medications was associated with lower 30-day rehospitalization rates and longer time-to-readmission. Physicians' adherence to treatments with higher-ranked evidence for efficacy, safety, and tolerability may improve bipolar disorder outcomes.

Barriers to and facilitators of success for early and Mid-Career professionals focused on bipolar disorder: A global needs survey by the International Society for Bipolar Disorders.

INTRODUCTION: The International Society for Bipolar Disorders created the Early Mid-Career Committee (EMCC) to support career development of the next generation of researchers and clinicians specializing in bipolar disorder (BD). To develop new infrastructure and initiatives, the EMCC completed a Needs Survey of the current limitations and gaps that restrict recruitment and retention of researchers and clinicians focused on BD. METHODS: The EMCC Needs Survey was developed through an iterative process, relying on literature and content expertise of workgroup members. The survey included 8 domains: navigating transitional career stages, creating and fostering mentorship, research activities, raising academic profile, clinical-research balance, networking and collaboration, community engagement, work-life balance. The final survey was deployed from May to August 2022 and was available in English, Spanish, Portuguese, Italian, and Chinese. RESULTS: Three hundred participants across six continents completed the Needs Survey. Half of the participants self-identified as belonging to an underrepresented group in health-related sciences (i.e., from certain gender, racial, ethnic, cultural, or disadvantaged backgrounds including individuals with disabilities). Quantitative results and qualitative content analysis revealed key barriers to pursuing a research career focused on BD with unique challenges specific to scientific writing and grant funding. Participants highlighted mentorship as a key facilitator of success in research and clinical work. CONCLUSION: The results of the Needs Survey are a call to action to support early- and midcareer professionals pursuing a career in BD. Interventions required to address the identified barriers will take coordination, creativity, and resources to develop, implement, and encourage uptake but will have long-lasting benefits for research, clinical practice, and ultimately those affected by BD.

Practices, knowledge, and attitudes about lithium treatment: Results of online surveys completed by clinicians and lithium-treated patients.

BACKGROUND: Lithium remains the gold-standard medication for acute and prophylactic treatment of bipolar disorder. Understanding clinicians' practices and patients' experiences, knowledge and attitudes about lithium may improve its clinical use. METHODS: Online anonymous surveys collected information about clinician's practices and level of confidence in managing lithium and patients' experiences with lithium treatment and information received about benefits and side effects. Knowledge and attitudes regarding lithium were assessed with the Lithium Knowledge Test (LKT) and the Lithium Attitudes Questionnaire (LAQ). RESULTS: Among 201 clinicians, 64.2% endorsed often treating patients with lithium and reported high levels of confidence in assessing and managing lithium. Practices concerning clinical indications, drug titration, and serum levels were guideline-concordant, but compliance with monitoring recommendations was less frequent. Practitioners were interested in receiving more education about lithium. The patients' survey recruited 219 participants with 70.3% being current lithium users. Most patients (68%) found lithium helpful and 71% reported experiencing any kind of side effect. Most responders did not receive information about side effects or other benefits of lithium. Patients with higher scores on the LKT were more likely to have positive attitudes about lithium. LIMITATIONS: Cross-sectional design with predominantly English-speaking participants from Brazil and North America. CONCLUSIONS: There is a discrepancy between guidelines, clinician confidence and knowledge of lithium use and practice. A deeper understanding of how to monitor, prevent and manage long-term side effects and which patients are most likely to benefit from lithium may narrow the gap between knowledge and use.

The concept of "metabolic jet lag" in the pathophysiology of bipolar disorder: implications for research and clinical care.

Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. "Metabolic jet lag" refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed through behavioral changes such as irregularities in sleep and appetite. Risk factors include genetic variation, mitochondrial dysfunction, lifestyle factors, poor gut microbiome health and abnormalities in hunger, satiety, and hedonistic function. Evidence suggests metabolic jet lag is a core component of BD pathophysiology, as individuals with BD frequently exhibit irregular eating rhythms and circadian desynchronization of their energetic metabolism, which is associated with unfavorable clinical outcomes. Although current diagnostic criteria lack any assessment of eating rhythms, technological advancements including mobile phone applications and ecological momentary assessment allow for the reliable tracking of biological rhythms. Overall, methodological refinement of metabolic jet lag assessment will increase knowledge in this field and stimulate the development of interventions targeting metabolic rhythms, such as time-restricted eating.

Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression.

IMPORTANCE: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years. EVIDENCE REVIEW: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS. FINDINGS: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, -0.35 [95% confidence interval, -0.68 to -0.03; P = 0.0351]; AS: standardized mean difference, -0.74 [95% CI, -1.37 to -0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression. CONCLUSIONS AND RELEVANCE: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.

Is there a place for dietetic interventions in adult ADHD?

Current treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in adults are limited by lack of response and side effects in about one third of the individuals. Changes towards a healthier lifestyle could have a positive impact beyond the relief of specific symptoms. However, it is not clear if nutritional interventions influence mental health and cognition. The objective of this study was to summarize the available literature addressing the impact of different diets in ADHD. The most promising dietetic approaches in ADHD are diets considered to be healthy (Mediterranean-type; DASH) and the Few-Foods Diet for children. Studies should take into account the presence of multiple confounders, biases associated with difficulties in blinding participants and researchers, and search for possible mechanisms of action, so we can have better evidence to guide clinical mental care of adults with ADHD.

A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges.

Purpose: Despite recent advancements in the treatment of depression, the prevalence of affected individuals continues to grow. The development of new strategies has been required and emerging evidence has linked a possible antidepressant effect with dietary interventions. In this review, we discuss recent findings about the possible antidepressant effect of dietary interventions with an emphasis on the results of randomized controlled trials. Recent findings: A high consumption of refined sugars and saturated fat and a low dietary content of fruits and vegetables has been associated with the development of depression. There is evidence supporting a small to moderate beneficial effect of a Mediterranean-type diet in depression. In addition, new dietary protocols are being studied for their use as possible interventions, such as the ketogenic diet, Nordic diet, and plant-based diet. Summary: Lifestyle interventions surrounding diet and nutrition are a relatively affordable way to enhance response to treatment and to be employed as an adjunct in mental health care. Most studies, however, are limited by the difficulty in controlling for the placebo effect. Mediterranean-style diets seem to be the most promising as an adjunctive treatment for mood disorders. Larger randomized controlled trials that could assess predictors of response to dietary interventions are needed to establish a clear positive effect of diet and guide clinical care and nutritional recommendations concerning mental health care.

Postictal Trismus Complicating Electroconvulsive Therapy: A Case Report.

We report a case of a 72-year-old woman who experienced postictal episodes of trismus lasting several minutes on 6 occasions during a series of 18 episodes of electroconvulsive therapy (ECT). There was no clear relationship between the development of trismus and any medications used during the treatments. The patient had no adverse outcomes or discomfort, but the development of trismus can put patients at significant risk.

What not to use in bipolar disorders: A systematic review of non-recommended treatments in clinical practice guidelines.

BACKGROUND: Clinical practice guidelines (CPG) are an important tool for implementation of evidence-based clinical care. Despite clinical trials showing lack of efficacy of some agents in bipolar disorder (BD), they are still frequently prescribed in clinical practice. The objective of this study was to systematically review the CPG recommendations on pharmacological interventions with evidence against their use due to lack of efficacy data and/or due to serious safety concerns. METHODS: A systematic literature search identified 29 guidelines published by national and international organizations during the 1994-2020 period. Information was extracted regarding how the recommendations framed non-use of treatments in particular clinical situations as well as the actual recommendation in the guideline. RESULTS: Twenty-three guidelines (79%) mentioned at least one non-recommended treatment. The terms used to qualify recommendations varied amongst guidelines and included: "not recommended" "no recommendation" and "negative evidence". Lamotrigine, topiramate and gabapentin were commonly cited as non-recommended treatments for mania and most CPG did not recommend monotherapy with antidepressants, aripiprazole, risperidone, and ziprasidone for treatment of acute bipolar depression. Most guidelines made recommendations about lack of efficacy data or potential harm in treatments for BD but there is a significant variation in the way this information is conveyed to the reader. LIMITATIONS: Non-recommended treatments were based on their use for BD episodes or maintenance but specific medications may benefit patients when treating comorbid conditions. CONCLUSIONS: The absence of a uniform language and recommendations in current guidelines may be an additional complicating factor in the implementation of evidence-based treatments in BD.