There has been debate about the frequency and severity of antidepressant withdrawal effects.

We set out to appraise and reanalyze an influential systematic review by Henssler and colleagues that concluded that withdrawal effects are not particularly common and rarely severe. We repeated the meta-analysis, including only studies where data were derived from systematic measures of withdrawal symptoms.

Most data in the Henssler review are derived from pharmaceutical industry–sponsored efficacy studies in which withdrawal was a minor consideration. Shortcomings of the review include the use of spontaneously reported adverse events to estimate withdrawal symptoms, potential misclassification of withdrawal symptoms as relapse, inclusion of data from retrospective case-note studies, short duration of prior antidepressant use, short observation periods, the overlooking of differences between placebo and drug withdrawal effects, and the use of questionable proxies for severe withdrawal. There were also discrepancies and uncertainties in some figures used. In our reanalysis, we included only the five studies that used a systematic and relevant method to assess the incidence of any withdrawal symptom. Prior treatment was short-term (12 weeks or less) in all but one of these. The pooled percentage was 55% (95% confidence interval, CI, 31% to 81%; N = 601) without subtracting nocebo effects, with high heterogeneity.

Henssler’s review is based on unreliable data and does not provide an adequate basis for the evaluation of antidepressant withdrawal effects. Further good-quality research on antidepressant withdrawal is required.

In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

Teva Branded Pharmaceutical Products R&D Inc.

Study Registration Number: NCT03893825

Neoclassical economics (NCE) theory and neoliberal economics practice together form one of the principal driving forces of environmental destruction and social injustice. We critically examine ten key hypotheses that form the foundations of NCE, and four other claims. Each fails to satisfy one or more of the basic requirements of scientific practice. Hence, NCE is fundamentally flawed, is irrational in the common meaning of the word, and should not be used as a guide for government policies. Because NCE is socially constructed, it can be replaced with an interdisciplinary conceptual framework that is compatible with ecological sustainability and social justice.

Neoclassical economics (NCE) is widely regarded as providing theoretical justification for neoliberal notions such as ‘governments should minimize regulation and spending, and hence leave major socioeconomic and environmental decisions to the market’. A large body of literature finds that NCE is largely responsible for environmental destruction and social inequality. As NCE is claimed to be a science and has appropriated terminology (without the content) from physics, we examine critically its basic hypotheses and four other claims from a viewpoint of natural scientists and an ecological economist, each a sustainability researcher. This paper defines NCE in two ways: as a theoretical structure for economics based on (1) the hypotheses of methodological individualism, methodological instrumentalism and methodological equilibration, and (2) the three hypotheses named above together with seven other common hypotheses of NCE. We find that each hypothesis and claim fails to satisfy one or more basic requirements of scientific practice such as empirical confirmation, underlying credible or empirical assumptions, consistency with Earth system science, and internal consistency. Sensitivity analysis is rare and ability to predict is lacking. Therefore, we recommend that neoclassical microeconomics be reformed and neoclassical macroeconomics be abandoned and replaced with a transdisciplinary field such as social ecological economics.

Conventional economics, a driver of environmental damage and social inequality, fails examination by sustainability scientists.

Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.

Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.

In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.

This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

Accurate triage is crucial for pediatric patients because their physiological differences make them more vulnerable to traumatic injury and mortality. However, pediatric trauma patients are challenging for EMS personnel for several reasons including infrequent clinical encounters and inadequate training. Despite the need for increased training, little is known about EMS readiness to perform triage and lifesaving interventions during pediatric mass casualty incidents (MCIs). Simulation skills assessment correlates with EMS performance in the field and can be used to determine MCI readiness.Pediatric patients are often omitted from MCI training and protocols. Feedback from EMS clinicians who participate in pediatric MCI simulations may be useful for educators seeking to optimize pediatric mass shooting triage training.

This was an observational study assessing EMS clinician accuracy in triaging eight children and two adults in a mass shooting simulation involving intimate partner violence (IPV) set at a private residence. Participating EMS clinicians were attendees of continuing education classes at Yale New Haven Health Centers for EMS. Participants worked in pairs, and triage decisions were documented during the simulation with an evaluation tool and video recording. After the simulation, pairs completed the demographic survey and completed a semi-structured debriefing. Facilitator prompts included correct triage level for each patient, the role IPV plays in mass shootings, and the participants feedback. Recordings of the debriefings were transcribed and analyzed using grounded theory. During the evaluation process, the major themes will be identified and coded. The transcriptions will be re-evaluated and any additional sub-themes will be identified and coded.

As of November 2022, eight paramedics have participated with more sessions scheduled for spring 2023. A preliminary review indicates potential themes will fall under the categories of simulation implementation and clinical approach to triage.

These findings may assist EMS agencies with their pediatric MCI training and response.