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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.
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.
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.
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.
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.