Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.

We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p < 0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Positively experienced relationships with family, partners and friends are the most important source of meaning in life for older persons. At the same time, Western countries are confronted with a growing number of socially isolated older adults who lack those relationships. This study aims to explore whether and how older adults who live in social isolation experience meaning in life. Data were collected via in-depth, semi-structured interviews with 24 socially isolated older adults, ranging in age from 62 to 94, all living in Rotterdam, The Netherlands. The criterion-based sampling of participants took place in close consultation with social workers of a mentoring project for socially isolated older adults. Follow-up interviews with 22 participants improved the credibility of findings and contributed to the breadth and depth of the researched casuistry. Data were analysed using an analytical framework based on seven needs of meaning identified by Baumeister (purpose, values, efficacy, self-worth) and Derkx (coherence, excitement, connectedness). The study demonstrates that isolated older adults may find anchors for meaning in life, although not all needs for meaning are satisfied, and there can also be tension between different needs. The needs-based model provides concrete distinctions for enabling care-givers to recognise elements of meaning.

Six field experiments were established in southwestern Ontario in 2021 and 2022 to evaluate whether the addition of a grass herbicide (acetochlor, dimethenamid-p, flufenacet, pendimethalin, pyroxasulfone, or S-metolachlor) to tolpyralate + atrazine improves late-season weed control in corn. Tolpyralate + atrazine caused 12% and 5% corn injury at 1 and 4 wk after herbicide application (WAA); corn injury was not increased with the addition of a grass herbicide. Weed interference reduced corn yield 60%. The addition of a grass herbicide to tolpyralate + atrazine did not enhance velvetleaf control. The addition of acetochlor or dimethenamid-p to tolpyralate + atrazine enhanced pigweed species control 4% 4 WAA; the addition of other grass herbicides tested did not increase pigweed species control. The addition of acetochlor enhanced common ragweed control 5% at 4 WAA, and the addition of acetochlor or dimethenamid-p enhanced common ragweed control 8% at 8 WAA; the addition of other grass herbicides did not improve common ragweed control. The addition of acetochlor to tolpyralate + atrazine enhanced common lambsquarters control up to 4%; there was no enhancement in common lambsquarters control with the addition of the other grass herbicides. Tolpyralate + atrazine controlled barnyardgrass 90% and 78% at 4 and 8 WAA, respectively; the addition of a grass herbicide enhanced barnyardgrass control 9% to 10% and 21% at 4 and 8 WAA, respectively. Tolpyralate + atrazine controlled green or giant foxtail 80% and 69% at 4 and 8 WAA, respectively; the addition of a grass herbicide enhanced foxtail species control 15% to 19% and 24% to 29% at 4 and 8 WAA, respectively. This research shows that adding a grass herbicide to tolpyralate + atrazine mixture can improve weed control efficacy, especially increased annual grass control in corn production.

A significant percentage of people with bipolar disorder (BD) exhibit suboptimal functional adjustment, even when appropriately treated and after symptomatic recovery is achieved. Given that cognitive impairment is one of the strongest correlates of socio-occupational outcomes and quality of life in BD, cognitive remediation (CR) is currently acknowledged as a promising treatment that could help bridge the gap between symptomatic and full functional recovery. The aim of this review was to explore the efficacy of CR approaches in improving cognitive and functional outcomes in BD patients. PubMed, PsycINFO, and CENTRAL were searched from inception to November 2022. Randomized controlled trials exploring the effects of CR on cognition and/or functional adjustment in adult BD patients were eligible. Ten studies based on seven independent trials (n = 586) were included. Change-score effect sizes (Hedges' g) were obtained for efficacy outcome measures and combined by means of meta-analytic procedures. Small but significant overall effects were observed for working memory (g = 0.32, 95% CI 0.11–0.52), planning (g = 0.30, 95% CI 0.03–0.56), and verbal learning (g = 0.40, 95% CI 0.15–0.66). However, CR was not found to exert any significant effects on functional outcomes at treatment completion or at follow-up assessment. Although CR may modestly enhance the cognitive performance of BD patients, this effect does not translate into an improvement at the functional level. The current data do not support the inclusion of CR as a treatment recommendation in clinical practice guidelines for the management of BD.

Interim analyses in clinical trials can take on a multitude of forms. They are often used to guide Data and Safety Monitoring Board (DSMB) recommendations to study teams regarding recruitment targets for large, later-phase clinical trials. As collaborative biostatisticians working and teaching in multiple fields of research and across a broad array of trial phases, we note the large heterogeneity and confusion surrounding interim analyses in clinical trials. Thus, in this paper, we aim to provide a general overview and guidance on interim analyses for a nonstatistical audience. We explain each of the following types of interim analyses: efficacy, futility, safety, and sample size re-estimation, and we provide the reader with reasoning, examples, and implications for each. We emphasize that while the types of interim analyses employed may differ depending on the nature of the study, we would always recommend prespecification of the interim analytic plan to the extent possible with risk mitigation and trial integrity remaining a priority. Finally, we posit that interim analyses should be used as tools to help the DSMB make informed decisions in the context of the overarching study. They should generally not be deemed binding, and they should not be reviewed in isolation.

The number of grassroots members of populist radical right (PRR) parties is on the rise, in contrast to the trend of membership decline in mainstream parties. While scholars have explained this by studying PRR parties' organizational strategies, I focus on party members and ask: Why do people join PRR parties? To answer this, I look not only at motivations, which is the dominant framework in party membership studies, but also at triggers – factors activating those motivations. Drawing on collective action scholarship, I argue that grievances and efficacy can work as triggers for joining PRR parties. Using interviews with 82 members of the Bharatiya Janata Party, the League in Italy and the Sweden Democrats, I uncover three elements in the path to PRR party membership: disaffection, affiliation and action. As well as questioning established narratives on why citizens join parties, my findings provide a novel theoretical framework to investigate this form of political participation.