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wilson interval - TitleWords in its title
title:mandelbrot - SummaryWords in its Summary, the paper’s abstract
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published:2026-10-01..2026-10-15 - ImportanceIts importance score, such as 70 or more
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cites:doi:10.1214/ss/1009213286 - IsRetracted, a correction, or scored
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Studies
- Its version 1’s most important claim’s importance 62 out of 100: meaningful importance, under edition 3 of the rubric
Whether antidepressants raise suicidal behaviour in adults is disputed: the FDA's pooled trials found no increase past young adulthood, and re-analyses of approval data on newer drugs found more suicide attempts. We tested this in the serious adverse events placebo-controlled trials posted to ClinicalTrials.gov, under a registered plan. This version corrects the first, which counted a participant listed under two of an outcome's terms twice. With the posted tables and the trials' public reports, serious suicidal behaviour affected 43 adults on antidepressants and 17 to 18 on placebo (risk ratio 1.86 to 1.96): nominally significant, but at the least favourable count not after the registered correction for two endpoints. Without the trials the re-analyses also used, the excess is similar but less certain. Pediatric trials showed more serious suicidality on antidepressants, as the FDA found. These data lean toward more suicidal behaviour in adults but cannot establish it.
- Published, Reproduced: Of the 932 interventional studies naming an antidepressant with results posted on ClinicalTrials.gov on 2026-10-13, 393 randomized trials compare an antidepressant with placebo in 413 comparisons with 99,730 participants at risk in their adverse-event tables. In the 306 adult trials that randomized participants from the start (71,643 participants), nausea is more frequent on antidepressants in the 207 comparisons whose non-serious tables list it (57,580 participants; Mantel-Haenszel risk ratio 2.08, 95% CI 1.98 to 2.18), as these drugs' known side effects predict.
- Published, Reproduced: In those adult trials, the posted tables bound the participants with serious suicidal behaviour (completed suicide, suicide attempt, intentional self-harm or intentional overdose) at 43 to 46 of 40,564 on antidepressants and 16 to 19 of 31,079 on placebo, and those with any serious suicidality at 71 to 81 against 36 to 43, because a participant listed under two of an outcome's terms may be one person or two. Across every count the tables allow, the Mantel-Haenszel risk ratio is 1.76 to 2.20 for serious suicidal behaviour (p 0.0097 to 0.0502) and 1.29 to 1.73 for any serious suicidality (p 0.0078 to 0.20). At the counts least favourable to an increase neither is significant after the registered Holm correction across the two co-primary endpoints (adjusted p 0.10 and 0.20); at the most favourable both are (0.016 and 0.016).
- Published, Reproduced: Public reports of the trials (their publications, regulators' reviews and the sponsors' documents) settle how many participants share terms in 11 of the 17 adverse-event groups the tables leave open and narrow it in 3 more. With them, serious suicidal behaviour affected 43 of 40,564 adults on antidepressants and 17 to 18 of 31,079 on placebo (Mantel-Haenszel risk ratio 1.86 to 1.96; p 0.025 to 0.036), and any serious suicidality 72 to 77 against 40 to 41 (1.38 to 1.51; p 0.041 to 0.12). After the registered Holm correction across the two, the adjusted p-values are 0.071 and 0.12 at the counts least favourable to an increase and 0.0496 for both at the most favourable.
- Its version 1’s most important claim’s importance 59 out of 100: meaningful importance, under edition 3 of the rubric
Ketamine relieves depression within a day, but patients feel its psychoactive effects, so its benefit could depend on that experience. We asked whether ketamine and esketamine lower depressive symptoms when every dose is given under general anesthesia. Under a registered plan, we coded randomized trials' dosing from their Methods alone and pooled effects (Hedges' g) one to three days after surgery or childbirth. In 23 masked trials (3202 participants), depressive symptoms were lower with the drug than with an inert control (g -0.61, confidence interval -0.81 to -0.4; Holm-adjusted p < 0.001), though trials varied widely. Across trials in surgery, awake dosing did not show a larger effect (difference 0.12, -0.24 to 0.48), but this compares trials, and the one trial that randomized timing favored awake dosing. Masked doses also lowered pain. Ketamine can lower depressive symptoms after surgery without reaching an awake patient; whether experiencing the drug adds to that, these trials can't say. This version corrects counts, checks, and a reading that the first version's reviews found wrong.
- Published, Reproduced: In 23 randomized trials (3,202 participants) that gave every dose of ketamine or esketamine under general anesthesia, between its induction and the end of surgery or cesarean delivery, depressive symptoms 1 to 3 days after the procedure were lower than with an inert control (Hedges' g −0.61, 95% CI −0.81 to −0.40; Holm-adjusted p < 0.001), though the trials varied widely (95% prediction interval −1.51 to 0.29). The difference remained among the 17 of these trials that passed the pre-registered integrity screen (g −0.48, −0.63 to −0.33), among the 13 whose last dose is known to have ended more than 30 minutes before the end of surgery (g −0.67, −1.04 to −0.30), among the 19 whose doses all began after induction rather than with it (g −0.60, −0.85 to −0.36), and with any single trial left out (largest p < 0.001).
- Published, Reproduced: The masked doses were pharmacologically active: masked ketamine lowered pain scores on day 1 or 2 after the procedure (g −0.55, 95% CI −0.97 to −0.14; 22 trials; g −0.38, −0.54 to −0.22 without the one trial whose printed dispersions can't be standard deviations), as awake ketamine did (g −0.33, −0.54 to −0.11; 32 trials; awake minus masked in surgery +0.32, −0.21 to 0.86). Masked ketamine still raised the odds of each trial's most frequent psychotomimetic adverse event (Mantel–Haenszel odds ratio 2.11, 1.48 to 2.99, in 22 trials), and awake ketamine raised them more (3.63, 2.97 to 4.43, in 40 trials): p = 0.0083 for the difference in the registered comparison, and p = 0.21 when the odds ratio may vary between trials (ratio of odds ratios 1.69, 0.74 to 3.84).
- Published, Reproduced: The masked effect was also present in the 7 masked trials that enrolled only patients with depression or depressive symptoms (g −0.78, 95% CI −1.24 to −0.31), and later after the procedure: on days 4 to 14 (g −0.51, −0.90 to −0.13; 18 trials) and days 15 to 90 (g −0.54, −0.75 to −0.33; 11 trials). Among the masked trials whose doses all began after induction, the days 4 to 14 interval included zero (g −0.61, −1.33 to 0.12; 10 trials).
- Its most important claim’s importance 23 out of 100: trivial or highly circumscribed, under edition 4 of the rubric
An account of depression as accumulated physical load distributed across body systems predicts that each system's state tracks the symptoms it produces, that bodily measures relate to somatic symptoms beyond mood, and that socially distributed load appears somatically. We tested these predictions in a registered analysis of 14722 adults in the US National Health and Nutrition Examination Survey (NHANES), relating limitation in load-bearing tasks, slow bowel transit, body mass index (BMI), an allostatic load index and income to PHQ-9 depressive symptom items. Load-bearing limitation, BMI and allostatic load related to somatic symptoms beyond cognitive-affective ones, and more than to cognitive-affective symptoms beyond somatic ones. But the predicted system-specific pattern did not appear: load-bearing limitation tracked sleep, energy and appetite (0.2946) far more than slow transit did (0.0404). Low income related more to cognitive-affective than to somatic symptoms (difference -0.0996). Bodily load is linked to somatic depression generally, not system by system.
- Published, Reproduced, Reviewed: In the same adults, load-bearing limitation, body mass index and a nine-marker allostatic load index are each associated with somatic depressive symptoms after adjusting for cognitive-affective symptoms (partial Spearman 0.1916, 0.0558, 0.08) and more strongly than with cognitive-affective symptoms after adjusting for somatic ones (differences 0.0711, 0.0399, 0.0646; Holm-adjusted p 0.002, 0.016, 0.002), whereas slow bowel transit shows no such specificity (difference 0.0074, 95% CI -0.0209 to 0.0347).
- Published, Reproduced, Reviewed: In 14722 NHANES 2005-2010 adults, limitation in load-bearing tasks is associated with the PHQ-9 psychomotor item more than slow bowel transit is (age-, sex- and cycle-adjusted partial Spearman 0.2038 vs 0.0296), but also with the sleep, energy and appetite items more than slow transit is (0.2946 vs 0.0404; difference -0.2542, 95% CI -0.2762 to -0.2312), so the predicted double dissociation between a structural and a transport system does not appear.
- Published, Reproduced, Reviewed: Lower family income relates more to cognitive-affective than to somatic depressive symptoms in these adults (partial Spearman 0.1275 vs 0.0279; difference -0.0996, 95% CI -0.1299 to -0.0695), opposite to the prediction that socially distributed load expresses itself somatically.
- Its most important claim’s importance being rated, 0 of 4 ratings in
Guaranteed income, regular cash with no conditions, has been tested in many American cities and in national pilots, and its advocates expect it to improve mental health without reducing work. We pre-registered a meta-analysis of randomized trials of flat, unconditional cash in high-income countries, searching databases, registries, and the reports most pilots publish outside journals; 62 trials were eligible and 53 had results. About a year into payments, mental health was better in the cash arms by 0.09 standard deviations (CI 0.041 to 0.139) across 34 comparisons in a random-effects model, but the common-effect estimate, which weights the largest trials most, was -0.002 (-0.023 to 0.018), and smaller trials reported larger effects. Employment changed by 0.599 percentage points (-2.533 to 3.731), and the mental-health effect did not fade during payments. Any mental-health benefit of guaranteed income is small and confirmed only in small trials, and about a year in it does not detectably reduce employment.
- Published, Reproduced: In 34 comparisons from 32 randomized trials of recurring unconditional cash in high-income countries (16,834 people analysed), mental health about 12 months into payments was better in the cash arms by a pooled standardized mean difference of 0.090 (95% CI 0.041 to 0.139; Holm-corrected p = 0.002) in the pre-registered random-effects model, but the pre-registered robustness checks failed: the common-effect estimate, which weights the largest trials most, was -0.002 (-0.023 to 0.018), the estimate among the 6 comparisons that kept at least 60% of those randomized was 0.043 (-0.077 to 0.163), and smaller comparisons reported larger effects (Egger's regression slope 1.54, 95% CI 0.75 to 2.33; p < 0.001).
- Published, Reproduced: In exploratory analyses added after registration, the larger mental-health benefits came from small comparisons and from shares above a cut-off: the 7 comparisons with at least 500 people analysed pooled to 0.041 standard deviations (95% CI -0.079 to 0.161) against 0.107 (0.052 to 0.163) for the other 27, and estimates from scale scores pooled to 0.051 (0.007 to 0.096) against 0.233 (0.084 to 0.381) for shares above a cut-off converted to standard deviations (difference 0.147, 0.037 to 0.258).
- Published, Reproduced: Of the 32 eligible registered trials of unconditional cash whose primary completion or end date was at least 12 months before 2026-10-17, 8 had reported no results this review could find, among them the Chicago Resilient Communities Pilot (AEARCTR-0009656), registered with 11,915 participants.
- Its most important claim’s importance being rated, 0 of 4 ratings in
Spatiotemporal accounts of depression predict that the default mode network (DMN) integrates over the longest intrinsic timescales, longer than control and salience networks, and that depression lengthens DMN timescales, prolongs DMN-dominant states, narrows transitions between network states and tracks brooding rumination. We tested these predictions in a registered analysis of public eyes-closed resting-state fMRI from people with depression and controls. Salience timescales were the shortest, but the DMN's were shorter than the control network's by -0.0416 s (CI -0.07 to -0.0125), opposite to the predicted order. Depression did not change DMN timescales (AUC 0.4015, CI 0.2708 to 0.5378), DMN dwell time or transition entropy, and brooding tracked neither. These data do not support the tested predictions.
- Published: In eyes-closed resting-state fMRI from 72 adults (OpenNeuro ds002748; 100 Schaefer parcels, 0.01-0.1 Hz band-pass, TR 2.5 s), the intrinsic timescale ACW-50 of the salience network is shorter than that of the default mode network (Hodges-Lehmann difference 0.0391 s, 95% CI 0.0057 to 0.0731) and of the control network (0.0751 s, 0.0397 to 0.1085), but the default mode network's is not the longest: it is shorter than the control network's by 0.0416 s (95% CI 0.0125 to 0.07).
- Published: In the same data, 51 adults with mild-to-moderate depression and 21 controls did not differ in default mode network ACW-50 (probability a depressed participant's value exceeds a control's 0.4015, 95% CI 0.2708 to 0.5378), in mean dwell time of default-mode-dominant states (0.5131, 0.3679 to 0.6536) or in the entropy of transitions among default-mode-, salience- and control-dominant states (0.549, 0.3987 to 0.6975); the design had 80% power only for differences near an AUC of 0.70.
- Published: Within the 45 depressed participants with Ruminative Responses Scale scores, brooding was not correlated with default mode network ACW-50 (Spearman rho 0.1065, 95% CI -0.1848 to 0.3812) or with default-mode-dominant dwell time (rho -0.2063, -0.4732 to 0.0887).