Psychiatry
RCT: KarXT (xanomeline–trospium) demonstrates significant symptom reduction in schizophrenia compared to placebo – The Lancet
11 May, 2024 | 13:42h | UTCStudy Design and Population: The EMERGENT-2 study was a randomized, double-blind, placebo-controlled, flexible-dose, 5-week phase 3 trial conducted across 22 inpatient sites in the USA. It targeted adults aged 18–65 years diagnosed with schizophrenia, exhibiting a recent exacerbation in psychotic symptoms. A total of 252 participants, each with a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher and a Clinical Global Impression-Severity score of 4 or more, were enrolled and randomized equally into two groups to receive either the muscarinic receptor agonist KarXT (xanomeline–trospium) or a placebo.
Main Findings: KarXT significantly reduced the PANSS total scores from baseline to week 5, with a mean decrease of 21.2 points compared to 11.6 points in the placebo group (least squares mean difference -9.6; 95% CI -13.9 to -5.2; p<0.0001; Cohen’s d=0.61). All secondary endpoints were also met favorably for KarXT. Common adverse events for KarXT included constipation, dyspepsia, and nausea, but rates of extrapyramidal symptoms were similar between the two groups. The treatment was generally well tolerated with comparable discontinuation rates due to adverse events.
Implications for Practice: These results indicate that KarXT could represent a new class of antipsychotic treatment, diverging from traditional D2 dopamine receptor antagonists and instead leveraging muscarinic receptor activation. The promising outcomes observed in EMERGENT-2 suggest that KarXT has the potential to improve both positive and negative symptoms of schizophrenia while maintaining a favorable safety profile. Ongoing and future studies (EMERGENT-3, EMERGENT-4, and EMERGENT-5) will further elucidate the long-term efficacy and safety of KarXT.
Reference (link to abstract – $ for full-text):
Meta-analysis reveals 24% prevalence of eating disorders among individuals with insulin-dependent diabetes – Eat Behav
11 May, 2024 | 13:41h | UTCThis systematic review and meta-analysis evaluated the prevalence of eating disorder symptoms (EDS) in individuals aged 16 and older with insulin-dependent diabetes, covering both type 1 and type 2 diabetes. The study involved an extensive search across several databases including PubMed, Embase, Scopus, PsycINFO, and CINAHL, culminating in the inclusion of 45 studies. The meta-analysis revealed a pooled prevalence of EDS at 24% (95% CI 0.21–0.28), with prevalence reaching 27% (95% CI 0.24–0.31) among studies using the Diabetes Eating Problem Survey-Revised (DEPS-R), the most frequently utilized screening tool. Notably, the prevalence of EDS varied based on the screening tool used and was significantly associated with sex distribution; studies with a higher percentage of female participants (over 58%) reported a higher prevalence of EDS (30% vs. 18%, prevalence ratio 1.7). The study also highlighted a concerning prevalence of insulin omission, reported at 21% (95% CI 0.13–0.33). This analysis underscores the substantial occurrence of eating disorder symptoms among this patient population, emphasizing the need for tailored screening and interventions.
Reference (link to abstract – $ for full-text):
RCT: Cytisinicline shows promising results in enhancing vaping cessation among adults – JAMA Intern Med
11 May, 2024 | 13:35h | UTCStudy Design and Population: The ORCA-V1 study was a double-blind, placebo-controlled randomized clinical trial conducted across five US clinical sites from July 2022 to February 2023. It enrolled 160 adults who used nicotine e-cigarettes daily and expressed a desire to quit, but were not current cigarette smokers. Participants were predominantly middle-aged (mean age 33.6 years), with a slight female majority (51.9%).
Main Findings: The trial assessed cytisinicline, a plant-based alkaloid, compared to placebo over a 12-week period with follow-up to 16 weeks. Results showed that cytisinicline significantly increased continuous abstinence from e-cigarette use during the last four weeks of treatment (31.8% vs 15.1% with placebo; odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). The effect was less pronounced but still present during the four weeks post-treatment (23.4% vs 13.2% with placebo; odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). The medication was well-tolerated, with only 3.8% of the cytisinicline group discontinuing due to adverse events.
Implications for Practice: Cytisinicline offers a promising pharmacotherapy option for adults seeking to quit vaping, demonstrating both efficacy and safety in this trial. Further research in larger populations and over longer periods is needed to confirm these findings and fully establish cytisinicline’s role in treating nicotine e-cigarette dependence.
Reference (link to abstract – $ for full-text):
Meta-Analysis: Acute adverse effects of therapeutic psilocybin doses in treating depression and anxiety – JAMA Netw Open
7 May, 2024 | 15:29h | UTCThis meta-analysis examined the acute adverse effects of psilocybin when used in therapeutic doses for treating depression and anxiety. The study analyzed data from six randomized, double-blind clinical trials involving a total of 528 participants. Significant adverse effects identified included headaches, nausea, anxiety, dizziness, and elevated blood pressure, compared to controls. No significant risks of paranoia or transient thought disorder were associated with psilocybin use. Overall, the adverse effects were tolerable and typically resolved within 48 hours, although the study calls for further research into their management.
Reference (link to free full-text):
RCT: Acute impact of provoked anger on endothelial health in healthy adults – J Am Heart Assoc
4 May, 2024 | 13:00h | UTCThis study explored the immediate effects of negative emotions on vascular endothelial health in a sample of 280 healthy adults. Participants were assigned to recall tasks that induced feelings of anger, anxiety, sadness, or a neutral emotional state, followed by assessments of endothelial health. The primary measure, endothelium-dependent vasodilation (reactive hyperemia index), significantly deteriorated in the anger group compared to the neutral condition (mean change: 0.20±0.67 vs. 0.50±0.60; P=0.007). Anxiety and sadness did not significantly affect this measure. Additionally, there were no significant changes in endothelial cell-derived microparticles or endothelial progenitor cells across all conditions. The findings indicate that short-term anger provocation can impair endothelial function, suggesting a specific pathway by which anger could increase cardiovascular disease risk.
Reference (link to free full-text):
M-A: Psilocybin significantly reduces depression symptoms across diverse populations – The BMJ
4 May, 2024 | 12:51h | UTCStudy Design and Population:
This systematic review and meta-analysis synthesized data from randomized trials assessing the efficacy of psilocybin as a treatment for depression in adults. Researchers utilized five electronic databases for published literature and four databases for unpublished and international studies. The analysis included 436 participants, aged 36 to 60 years, from seven randomized trials, with both genders represented and varying comorbidities such as cancer.
Main Findings:
The meta-analysis revealed a significant reduction in depression scores among participants treated with psilocybin, with a Hedges’ g value of 1.64, indicating a large effect size. Notably, the improvement was more pronounced among those with secondary depression and those assessed using self-report depression scales. Subgroup analyses and metaregression also highlighted that older age and previous use of psychedelics correlated with greater symptom improvement. Despite the robust findings, high heterogeneity and a risk of small study bias led to a low certainty of evidence.
Implications for Practice:
The findings support psilocybin’s potential as an effective antidepressant, particularly among specific subgroups such as those with secondary depression. However, the presence of high heterogeneity and small study biases suggests that further research is needed to explore the impact of expectancy effects, moderating factors, and treatment modalities. Clinicians should consider these elements when discussing psilocybin as a treatment option with patients, and further high-quality studies are necessary to solidify its role in clinical practice.
Reference (link to free full-text):
RCT: Xanomeline-trospium reduces psychosis symptoms in patients with schizophrenia – JAMA Psychiatry
2 May, 2024 | 23:24h | UTCStudy Design and Population:
This study, titled EMERGENT-3 (NCT04738123), is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of xanomeline-trospium chloride in adults with schizophrenia experiencing acute psychosis. It involved 256 participants across 30 inpatient sites in the US and Ukraine, with the study period running from April 1, 2021, to December 7, 2022. Data analysis occurred from February to June 2023.
Main Findings:
The primary outcome was the change from baseline to week 5 in the Positive and Negative Syndrome Scale (PANSS) total score. Xanomeline-trospium significantly reduced the PANSS total score compared to placebo, with a least squares mean difference of -8.4 and a Cohen’s d effect size of 0.60. The most common adverse events were gastrointestinal, mild to moderate in intensity, and generally transient. Safety and tolerability profiles were favorable, with similar discontinuation rates due to adverse events between the xanomeline-trospium and placebo groups.
Implications for Practice:
The results of EMERGENT-3, alongside the consistent findings from earlier phases of the trial, affirm xanomeline-trospium’s potential as a novel class of antipsychotic medication. Its mechanism of action, which does not involve D2 dopamine receptor blocking, offers a promising alternative to traditional antipsychotics, particularly for patients who may benefit from different therapeutic approaches due to issues with current treatments.
Commentary on X:
Xanomeline-trospium is efficacious & well tolerated in people with schizophrenia experiencing acute psychosis, finds EMERGENT-3 trial, and supports potential of xanomeline-trospium to be first in a putative new class of antipsychotic medications. https://t.co/ioBCKOgvQa pic.twitter.com/CDmYEgYN2O
— JAMA Psychiatry (@JAMAPsych) May 1, 2024
Reference (link to free full-text):
Cohort Study: Metabolic biomarkers and long-term risk of psychiatric disorders in over 200,000 individuals
27 Apr, 2024 | 18:29h | UTCStudy Design and Population:
This population-based cohort study assessed 211,200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort, who underwent occupational health screening primarily in the Stockholm region of Sweden from 1985 to 1996. Participants were followed longitudinally, with statistical analysis performed between 2022 and 2023. The study included extensive biomarker measurements such as glucose, triglycerides, and high-density lipoprotein.
Main Findings:
The study found significant associations between certain metabolic biomarkers and the risk of developing psychiatric disorders such as depression, anxiety, and stress-related disorders. Specifically, high levels of glucose (HR, 1.30) and triglycerides (HR, 1.15) were linked to an increased risk of these disorders, while high levels of high-density lipoprotein (HR, 0.88) were associated with a reduced risk. These findings held true across both genders and all disorders tested, with nested case-control analyses confirming these trends.
Implications for Practice:
The study suggests that metabolic dysregulation, as indicated by specific biomarkers, may either increase the risk or be a marker of increased risk for the development of common psychiatric disorders. These findings support the potential for closer monitoring and follow-up of individuals with abnormal metabolic profiles to aid in the prevention and early diagnosis of psychiatric conditions.
Reference (free full-text):
RCT | Field sobriety tests display insufficient accuracy for detecting THC-specific driving impairment
11 Aug, 2023 | 15:14h | UTCSee also: Visual Abstract
News Release: Can field sobriety tests identify drivers under the influence of cannabis? – University of California – San Diego
Commentary on Twitter
This randomized clinical trial investigates the accuracy of field sobriety tests administered by law enforcement officers to assess functional impairment and driving performance among individuals who have smoked cannabis. https://t.co/pThOOdZGUh
— JAMA Psychiatry (@JAMAPsych) August 2, 2023
Review | Adverse effects of antidepressant medications and their management in children and adolescents
9 Aug, 2023 | 15:25h | UTC
M-A | Absence of evidence for antipsychotics in youth unipolar depression; limited evidence in bipolar depression
9 Aug, 2023 | 15:23h | UTC
Cohort Study | Clozapine, but not olanzapine or quetiapine, linked with higher perimyocarditis and heart failure risk
8 Aug, 2023 | 13:14h | UTC
Study | Gastric bypass linked to increased risk of non-alcohol substance use disorder
7 Aug, 2023 | 14:23h | UTCNews Release: Gastric bypass surgery associated with non-alcohol substance use disorder – Obesity – The Obesity Society
RCT | 52-week antidepressant adjunctive therapy did not lead to a statistically significant benefit over 8-week therapy in bipolar I depression
4 Aug, 2023 | 12:11h | UTCDuration of Adjunctive Antidepressant Maintenance in Bipolar I Depression – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Modern antidepressants may reduce risk of relapse for patients with bipolar depression – University of British Columbia
Commentary on Twitter
Among patients with bipolar I disorder who had remission of depression, there was no significant difference in the incidence of relapse of any mood episode between 8 weeks and 52 weeks of antidepressant treatment. Full results of the BEAM-BD trial: https://t.co/rCkCqIfMb6
— NEJM (@NEJM) August 2, 2023
Cohort Study | Increased mortality rates in delirium tremens patients versus alcohol withdrawal or dependence
3 Aug, 2023 | 13:35h | UTC
Study | Increasing alcohol-related mortality rates in US women, 1999-2020
3 Aug, 2023 | 13:20h | UTCTrends in Alcohol-Related Deaths by Sex in the US, 1999-2020 – JAMA Network Open
Commentary: As alcohol-related deaths rise in the US, women are increasingly at risk, study shows – CNN
Evidence Review | AA and other 12-step programs outperform CBT for alcohol use disorder
2 Aug, 2023 | 14:05h | UTCAlcohol dependence: evidence and experience on 12 steps to recovery – Evidently Cochrane
Original study: Alcoholics Anonymous and other 12‐step programs for alcohol use disorder – Cochrane Library
Cohort Study | Depression at any life stage linked to increased dementia incidence
2 Aug, 2023 | 13:49h | UTCAssociation of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort – JAMA Neurology (link to abstract – $ for full-text)
Commentary: Depression Over Adulthood May Increase Risk of Dementia – Psychiatric News Alert
Systematic Review | Organizational changes likely decrease physical restraint usage in long-term care
31 Jul, 2023 | 13:53h | UTC
Phase 2 Trial | Oral orexin receptor 2 agonist shows promise in narcolepsy type 1, but raises hepatotoxic concerns
28 Jul, 2023 | 14:09h | UTCOral Orexin Receptor 2 Agonist in Narcolepsy Type 1 – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
In a randomized trial involving patients with narcolepsy, an oral orexin receptor 2 agonist reduced sleepiness and cataplexy but had liver toxic effects. Read the full trial results: https://t.co/Go7lmQTu62
— NEJM (@NEJM) July 26, 2023
RCT | Zuranolone, a potential rapid-acting oral treatment for severe postpartum depression
27 Jul, 2023 | 13:00h | UTCZuranolone for the Treatment of Postpartum Depression – American Journal of Psychiatry (link to abstract – $ for full-text)
Commentary: Postpartum Depression Pill Zuralonone Shows Promise in Women With Severe Symptoms – Psychiatric News Alert
Related: RCT | Zuranolone outperforms placebo in major depressive disorder treatment
Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness
26 Jul, 2023 | 13:28h | UTC
Systematic Review | Existing research on post-stroke depression interventions lacks conclusive results
25 Jul, 2023 | 13:37h | UTC
Cohort Study | Increased risk of depression and suicide among people with HIV, especially in the first two years post-diagnosis
24 Jul, 2023 | 13:01h | UTC
Commentary on Twitter
Risk of Depression in People With HIV: A nationwide population-based matched cohort study
✅ Just Accepted
? Freely Availablehttps://t.co/nyrzPqRRqw— Clinical Infectious Diseases (@CIDJournal) July 22, 2023
RCT | Online emotion regulation therapy yields significant reduction in adolescent self-injury
24 Jul, 2023 | 12:39h | UTCSee also: Visual Abstract
News Release: Internet-based therapy effective against self-harm in adolescents – Karolinska Institutes