Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Functional traits and phylogenetic analysis of top-soil inhabiting rhizobacteria associated with tea rhizospheres in North Bengal, India.

Rhizobacteria associated with cultivated crops are known to stimulate plant growth through various indirect or direct mechanisms. In recent years, the host list of plant growth promotion/promoting rhizobacteria has expanded to include bean, barley, cotton, maize, rice, vegetables, peanut, rice, wheat, and several plantation crops. However, interaction of rhizobacteria with tea plants of organic and conventional tea gardens is poorly understood. In the present study, rhizobacterial species associated with tea rhizosphere were isolated from 14 tea gardens located in North Bengal, India. In total, 16 rhizobacterial isolates isolated from collected soil samples were assessed for antagonistic and plant growth promotion/promoting activity under laboratory conditions. Molecular characterization based on sequencing of 16S rRNA gene revealed dominance of Bacillus with five species followed by Pseudomonas with two species. Interestingly, only one isolate was affiliated with actinobacteria, i.e., Microbacterium barkeri. Out of 16 isolates, isolates Bacillus subtilis OKAKP01, B. subtilis BNLG01, B. paramycoides BOK01, M. barkeri BPATH02, and Stenotrophomonas maltophilia BSEY01 showed highest growth inhibition against Fusarium solani (68.2 to 72.8%), Pseudopestalotiopsis theae (71.1 to 85.6%), and Exobasidium vexans (67.4 to 78.3%) causing respective Fusarium dieback, gray blight, and blister blight diseases in tea crop. Further, these five isolates also possessed significantly greater antifungal (siderophore producer, protease, chitinase, and cellulase activity) and plant growth promotion/promoting (indole-3-acetic acid production, ACC deaminase, ammonia, and phosphate solubilization) traits over other eleven rhizobacterial isolates. Therefore, these five isolates of rhizobacteria were chosen for their plant growth promotion/promoting activity on tea plants in nursery conditions. Results from nursery experiments revealed that these five rhizobacteria significantly improved growth rates of tea plants compared with the control. Therefore, this study suggests that these rhizobacteria could be used to formulate biopesticides and biofertilizers, which could be applied to sustainable tea cultivation to improve crop health and reduce disease attack.

Psychophysiological Arousal in Young Children Who Stutter: An Interpretable AI Approach.

The presented first-of-its-kind study effectively identifies and visualizes the second-by-second pattern differences in the physiological arousal of preschool-age children who do stutter (CWS) and who do not stutter (CWNS) while speaking perceptually fluently in two challenging conditions: speaking in stressful situations and narration. The first condition may affect children's speech due to high arousal; the latter introduces linguistic, cognitive, and communicative demands on speakers. We collected physiological parameters data from 70 children in the two target conditions. First, we adopt a novel modality-wise multiple-instance-learning (MI-MIL) approach to classify CWS vs. CWNS in different conditions effectively. The evaluation of this classifier addresses four critical research questions that align with state-of-the-art speech science studies' interests. Later, we leverage SHAP classifier interpretations to visualize the salient, fine-grain, and temporal physiological parameters unique to CWS at the population/group-level and personalized-level. While group-level identification of distinct patterns would enhance our understanding of stuttering etiology and development, the personalized-level identification would enable remote, continuous, and real-time assessment of stuttering children's physiological arousal, which may lead to personalized, just-in-time interventions, resulting in an improvement in speech fluency. The presented MI-MIL approach is novel, generalizable to different domains, and real-time executable. Finally, comprehensive evaluations are done on multiple datasets, presented framework, and several baselines that identified notable insights on CWSs' physiological arousal during speech production.

Outcomes of Neuroleptic Malignant Syndrome With Depot Versus Oral Antipsychotics: A Systematic Review and Pooled, Patient-Level Analysis of 662 Case Reports.

OBJECTIVE: This systematic review and pooled, patient-level analysis of neuroleptic malignant syndrome (NMS) case reports and series compared NMS characteristics and outcomes during long-acting injectable antipsychotic (LAI) versus oral antipsychotic (OAP) treatment. DATA SOURCES: Two authors independently searched MEDLINE, Embase, Cochrane, CINAHL, and PsycINFO databases for articles in English from database inception until October 9, 2018. STUDY SELECTION: Case reports with author-defined NMS during ongoing antipsychotic treatment or within 1 injection interval of LAIs in adults aged 18-65 years. DATA EXTRACTION: Demographic, clinical, treatment and outcome data were independently extracted following PRISMA guidelines. NMS severity was rated using the Francis-Yacoub scale. Characteristics and outcomes of NMS were compared when occurring during LAI versus OAP treatment, adjusting for significant between-group differences. RESULTS: Of 662 reported cases (median age = 36 years, male = 61.2%), 122 (18.4%) involved LAIs (second-generation antipsychotic [SGA] LAIs [SGA-LAIs] = 10, 1.5%), whereas 540 (81.6%) involved OAPs (SGA-OAPs = 159, 24.0%). The 2 groups did not differ in age, illness duration, comorbidities, or presence or severity of NMS symptoms (median Francis-Yacoub score: LAIs = 26 vs OAPs = 23, P = .8276). Antipsychotic formulation was not significantly associated with longer duration of hospitalization (LAIs = 5.0 weeks vs OAPs = 3.8 weeks, P = .8322), post-NMS sequelae (LAIs = 8.8% vs OAPs = 7.0%, P = .7489), or death (LAIs = 10.7% vs OAPs = 6.7%, P = .0861). When different, post hoc confounder-adjusted models were used, duration of NMS (but not hospitalization for NMS) was longer with LAIs than with OAPs (median = 2.6 vs 1.8 weeks, P = .0339), driven by FGAs rather than SGAs. CONCLUSIONS: These data, plus the fact that only 10 published NMS cases exist with SGA-LAIs, should mitigate safety concerns regarding LAIs, but results should be interpreted cautiously since they are based on case reports.