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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.

• 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.

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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).

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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).

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