Every study, searchable

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.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.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.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.

6 more claims

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.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.Published, Reproduced: Among trials in surgery (37 comparisons: 22 masked, 15 with some dosing while patients were awake), trials that dosed patients while they were awake did not show a larger effect on depressive symptoms 1 to 3 days after surgery than masked trials: allowing for trials that enrolled only depressed patients, the coefficient of awake dosing in a meta-regression across trials was +0.12 (95% CI −0.24 to 0.48; p = 0.51), and the pooled effects in surgery were g −0.62 with masked and −0.45 with awake dosing. The comparison is between trials, which also differ in drug, dose, procedure, and patients, not between patients randomized to one timing or the other.
• Published, Reproduced.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).

4 more claims

An observational atlas linked GLP-1 receptor agonists to dozens of outcomes beyond glucose, weight and the heart. We pooled the serious adverse events that 234 placebo-controlled trials, with 161309 participants, posted to ClinicalTrials.gov, coded blind to the results under a registered plan. Reports of serious bacterial infection (ratio 0.88, confidence interval 0.83 to 0.93) and pneumonia (0.87) were less frequent on the drugs, as were pneumonia counted in people and death. The reductions held under random effects, with any trial left out, if infection terms overlapped within participants as all serious events do in each comparison, and in trials not coded as recording only on treatment. Of the atlas's associations with enough events to test, the trials found three in its direction with no difference from it detected, contradicted none, and left most inconclusive, among them every neurological and psychiatric one; its large hazard of drug-induced pancreatitis concerns a subtype the trials don't separate.

• Published, Reproduced.Published, Reproduced: Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants in their adverse-event tables (93,765 on the drugs and 67,544 on placebo). In them, reports of serious gallbladder and biliary disease, counting a participant once for each of the outcome's terms they had, are more frequent on the drugs (Mantel-Haenszel ratio 1.38, 95% CI 1.21 to 1.57), and so are reports of serious nausea and vomiting (2.02, 1.52 to 2.68), as the trials' own publications and the drugs' labels lead one to expect.
• Published, Reproduced.Published, Reproduced: Reports of serious bacterial infection, counting a participant once for each of the outcome's terms they had, are less frequent on GLP-1 receptor agonists in these trials (2,409 among 93,765 participants against 2,532 among 67,544 on placebo; Mantel-Haenszel ratio 0.88, 95% CI 0.83 to 0.93, q < 0.001), and so are reports of serious pneumonia (1,442 against 1,568; 0.87, 0.81 to 0.93, q = 0.0020); both stay significant under random effects and with any single trial left out. Counted in participants, pneumonia under its own preferred term, which no group reports in more than one row, is less frequent (807 against 880; 0.86, 0.79 to 0.95). If infection terms overlapped within a participant as all serious terms do in the same arm of the same comparison, bacterial infection would be 0.89 (0.82 to 0.97).
• Published, Reproduced.Published, Reproduced: In the registered scan without hypotheses of 27 organ systems and 518 preferred terms, with the same variance as the other claims, four organ systems (cardiac disorders; infections and infestations; metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders) and two preferred terms (acute myocardial infarction and cellulitis) are lower on the drugs with q < 0.05 in a random half of the trials and p < 0.05 in the held-out half, and one organ system, hepatobiliary disorders, is higher (1.36 in the first half, 1.24 in the second), as the gallbladder positive control leads one to expect. Among those lower are serious infection reports as a whole (0.88 and 0.89) and cellulitis (0.64 and 0.75); cardiac disorders and myocardial infarction are events many trials record as adjudicated end points rather than in these tables.

6 more claims

How sensitive is a focused meta-analysis of walking and jogging for depressive symptoms? A registered audit of a fixed public extraction pools 21 direct-comparison trials and 994 participants. Post-treatment Hedges g is -0.762, with a confidence interval from -1.203 to -0.321. Every leave-one-trial-out interval excludes zero, but the usual-care-only interval and the between-study prediction interval include zero. No included trial has an overall low-risk-of-bias rating. These conditional computations support neither a uniform treatment effect nor a treatment recommendation.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In the fixed Noetel et al. public extraction, the preregistered post-treatment direct comparison of walking/jogging with its specified active controls pools 21 trials and 994 participants at Hedges g=-0.762 (95% modified Hartung-Knapp confidence interval -1.203 to -0.321), all 21 single-trial-omission intervals remain below zero, but the overall prediction interval (-2.613 to 1.088) and usual-care-only confidence interval (-1.650 to 0.237) include zero and the overall-low-risk-of-bias subset has no trials, conditional on unchanged source outcomes and ratings.

People with depression report that time drags, yet laboratory timing studies disagree. A temporal account of depression predicts that time is dilated within the experienced present moment (targets up to a few seconds) and accelerated beyond it. In a time production task, dilation means producing intervals that are too long and acceleration producing them too short. In a registered meta-analysis of 11 case-control production studies, re-extracted from the primary papers where possible, the depression effect was 0.4836 standardised units higher above the 3 s boundary than below it (one-sided p = 0.03380082115675086), with overproduction at short targets (g = -0.2851) and underproduction at longer ones (g = 0.1985), neither significant alone. The effect rose by 0.6302 per tenfold increase in duration. Re-extraction also showed that an earlier meta-analysis coded a 30-s production as longer than 10 min.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Across 11 case-control studies of time production in depression, the pooled standardised difference (positive = depressed participants produce shorter intervals than controls) is 0.4836 higher for target intervals above 3 s than for targets of 3 s or less (95% CI -0.0431 to 1.0103; one-sided p = 0.034), with pooled g = -0.2851 at 3 s or less (3 studies; 95% CI -0.6917 to 0.1214) and g = 0.1985 above 3 s (10 studies; 95% CI -0.1378 to 0.5348).
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Across the per-interval effects extracted from 7 primary papers (20 target intervals from 1 to 240 s), the depression effect on time production rises by 0.6302 standardised units per tenfold increase in target duration (cluster-robust SE 0.2128; one-sided p = 0.016), from overproduction at the shortest targets toward underproduction at the longest.
• Published, Reviewed.Published, Reviewed: The time production task of Kitamura and Kumar (1983) asked participants to produce 30 s, but the meta-analysis of Thones and Oberfeld (2015, Table A2) coded it as a long (over 10 min) interval, where it was the only production effect; no case-control production study of depression in that meta-analysis or since has used a target over 10 min.

Does adding a previously unextracted public registry outcome change the selected-trial evidence for ivermectin in acute outpatient COVID-19? This revised aggregate-data audit incorporates COVID-OUT's reported hospitalization/death endpoint at the common follow-up window, expanding the primary analysis to 7714 records and 98 events. The exploratory pooled risk ratio is 1.107 (95% confidence interval 0.577 to 2.123). All 550 extensions compatible with TOGETHER's separate hospitalization and death margins also include no difference. The newly retrieved appendix does not identify their overlap. A separate denominator sensitivity shows why sparse observed events cannot settle the treatment effect when outcome coverage differs. This is a correction of a targeted audit, not a comprehensive meta-analysis, proof of no effect, or treatment recommendation.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Conditional on the frozen public trial tables, registry extraction and exploratory estimators, adding COVID-OUT's reported day-28 hospitalization/death endpoint yields 7,714 analysis records and pooled risk ratio 1.107 (95% modified Hartung-Knapp interval 0.577 to 2.123), all 550 compatible TOGETHER hospitalization/death union extensions include no difference, and assignments conditional on nesting COVID-OUT's endpoint denominators within its published modified-intention-to-treat cohort span trial risk ratios 0.083 to 7.766, establishing neither benefit nor equivalence.

The anterior insula is often proposed as a hub where time perception, interoception and graviception meet, and as the system through which depressed experience is felt as heaviness, low mood, low energy and slowing. Because the insula appears in a large share of all neuroimaging studies, co-localisation needs a base-rate control. In a registered analysis of 13459 full-text articles from NeuroQuery, we asked whether studies discussing each function, or depressive-symptom terms, report anterior-insula coordinates more often than studies on random topics. Interoception studies did (association z 10.259), but equally in the posterior insula; time perception (z {{R1.terms.time perception.anterior_insula.z}}) and vestibular studies (z -0.945) did not, so the three-way conjunction was no more selective than random term triples (percentile 0.5456). Symptom terms were not selective either (percentile 0.7064). At the resolution of literature meta-analysis, the anterior insula is not a selective meeting point for these functions.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Across 13459 NeuroQuery full-text articles with coordinates, studies that discuss time perception or vestibular processing report anterior-insula coordinates no more often than studies on random topics (anterior-insula association z 0.424 and -0.945; percentiles 0.4959 and 0.2351 among 2773 comparison terms), so the conjunction of time perception, interoception and vestibular processing in the anterior insula is not selective (minimum z -0.945, percentile 0.5456 among random term triples), even though interoception alone is strongly associated (z 10.259).
• Published, Reproduced.Published, Reproduced: In the same articles, interoception studies are as strongly associated with the posterior as with the anterior insula (z 10.389 vs 10.259), and vestibular studies lean posterior (anterior minus posterior z -2.366, percentile 0.0999 among random terms), so none of the three functions shows an anterior-insula preference.
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Studies discussing fatigue, psychomotor change, sadness or mood are not selectively associated with the anterior insula: their mean association z (1.057) lies at percentile 0.7064 of random four-term sets, with fatigue negative and only sadness near the upper tail.

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.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.Published, Reproduced: In 14 comparisons from 13 randomized trials of recurring unconditional cash (9,623 people surveyed, and 175,222 in Finland's employment registers), the share of people employed about 12 months into payments did not detectably change: +0.60 percentage points (95% CI -2.53 to 3.73; Holm-corrected p = 1.000), an interval that rules out a reduction larger than 2.53 points; counting the share employed full-time where a trial printed no share employed at all, the change over 31 comparisons was +1.13 points (-1.14 to 3.40).
• Published, Reproduced.Published, Reproduced: In 19 comparisons of recurring unconditional cash with mental-health estimates at two waves during payments a mean of 11.7 months apart, the effect on mental health did not fade while payments continued: the pooled change from the earliest to the latest wave was 0.000 standard deviations (95% CI -0.049 to 0.048; Holm-corrected p = 1.000), the effects at the two waves being 0.048 and 0.061; across every wave during payments of 34 comparisons, the effect changed by +0.015 standard deviations per year (-0.034 to 0.064).

4 more claims

Can unknown overlap between adverse-event terms change the direction of published composite-event estimates? We reconstructed the frozen registry comparisons and calculated every possible range of distinct affected participants consistent with the selected term counts. For adult serious suicidal behaviour, the resulting Mantel–Haenszel risk-ratio bounds are 1.712 to 2.1962; for adult serious suicidality, 1.2154 to 1.8476. The corresponding pediatric bounds are 1.0045 to 1.4773 and 1.8144 to 2.8091. All remain above the null. Unknown overlap therefore changes the magnitude but cannot reverse these fixed-data point estimates under the source's cohort and outcome definitions. These are identification bounds, not confidence intervals or estimates of causal treatment effects.

• Published, Reproduced.Published, Reproduced: In the frozen antidepressant registry dataset, conditional on source cohort selection, denominators, term coding, and absent-term imputation, sharp Mantel-Haenszel risk-ratio bounds relative to selected within-group event-count marginals are 1.7120261533 to 2.1961879882 for adult serious suicidal behaviour, 1.2154409158 to 1.8475901940 for adult serious suicidality, 1.0045047792 to 1.4773331886 for pediatric serious behaviour, and 1.8144436696 to 2.8090979871 for pediatric serious suicidality. Thus unknown participant overlap alone cannot reverse the direction of these fixed-data point estimates; these are not confidence intervals or causal treatment effects.

The World Health Organization's 2020 guideline recommended giving mass azithromycin, which lowers child mortality in high-mortality settings of sub-Saharan Africa, only to infants, to limit antibiotic resistance; no trial had then tested that. Under a pre-registered plan we pooled every randomized trial by whom it treated. Treating all children under five lowered their mortality by 14.1% (CI 7.4% to 20.3%), consistently across trials. In the three trials that treated only infants, infant mortality was not detectably lower (rate ratio 0.971, CI 0.867 to 1.086), an interval that excludes the effect of treating all children. Infants had lower mortality when all children were treated, though a between-trial comparison of the two strategies fell short of significance, and giving azithromycin to individual infants at clinic visits showed no effect. The infant-only approach has not lowered mortality in any trial that tested it; treating all children under five has.

• Published, Reproduced.Published, Reproduced: In 5 placebo-controlled comparisons from 3 cluster-randomized trials (MORDOR in Niger, Malawi and Tanzania; AVENIR in Niger; CHAT in Burkina Faso), twice-yearly mass azithromycin to every child 1 to 59 months old lowered mortality among children 1 to 59 months by 14.1% (rate ratio 0.859, 95% CI 0.797 to 0.926; Holm-corrected p = 0.015; I² = 0%), and the reduction held with a common-effect model (0.859, 0.813 to 0.908) and with any one comparison left out (largest p = 0.044).
• Published, Reproduced.Published, Reproduced: In the 3 cluster-randomized trials that gave azithromycin twice a year to infants 1 to 11 months old only, the approach the World Health Organization recommended in 2020 (AVENIR's infant arm in Niger, LAKANA in Mali, MIRAMA in Burkina Faso), infant mortality was not detectably lower than with placebo (rate ratio 0.971, 95% CI 0.867 to 1.086; p = 0.370), an interval that rules out a reduction larger than 13.3% and so excludes the 14.1% reduction seen when all children 1 to 59 months were treated; the estimate stayed near 1 with LAKANA's four-times-yearly arm instead (0.948, 0.856 to 1.050), without MIRAMA (0.963, 0.656 to 1.413), and with the 2 individually randomized infant trials added (0.969, 0.881 to 1.066).
• Published, Reproduced.Published, Reproduced: Infant mortality was lower when all children 1 to 59 months were treated (rate ratio 0.823, 95% CI 0.707 to 0.958; 3 comparisons) than when only infants were (0.971), but the pre-registered meta-regression comparing the two strategies across trials did not establish a difference (ratio of rate ratios 1.187, 95% CI 0.974 to 1.447; p = 0.074; Holm-corrected p = 0.148); AVENIR's within-trial contrast of its all-children arm against its infant arm, estimated after registration from the two arms' printed mortality rates, was 0.830 (0.717 to 0.959).

4 more claims