The evidence library

Caveat on this rating: A methods critique: it argues effects are overstated but does not measure by how much, and it does not show the drugs have no effect. Read from the abstract only.

Caveat on this rating: Observational, no placebo, self-selected through psychedelic-friendly venues, 180 comparators against 953 microdosers; the app maker's staff and a supplement seller with patents on the tested combination are co-authors. Randomised trials find no clear effect.

Caveat on this rating: Cross-sectional, self-selected app users recruited through psychedelic-friendly venues, with small effects; the app maker's founders and a patent holder are co-authors. Randomised trials (Meshkat 2026) find no clear effect.

Caveat on this rating: This is the regulator that approved the drug, describing its own doubts and why it approved anyway. It cannot say whether the placebo relapses were withdrawal, unblinding or true relapse; it says the reviewers could not tell.

Caveat on this rating: With 34 participants the study is underpowered to detect small true effects, and the authors' own Bayesian analysis in the successfully blinded subgroup was inconclusive rather than clearly negative.

Caveat on this rating: The meta-analytic estimates rest on very little randomised data — two parallel RCTs (three comparisons, n=117) for efficacy and two RCTs (n=109) for adverse events — so the confidence intervals are wide and the review is better read as demonstrating absence of evidence than proving absence of effect. Several authors are affiliated with psychedelic research centres and one is chief medical officer of a psychedelics company (disclosed), so the null result is not coming from sceptics.

Caveat on this rating: Read from the abstract and plain language summary only. Most included trials excluded young people at risk of suicide; suicide-related estimates are low certainty with wide intervals. The 2026 re-appraisal authors report that the full dataset behind this review was not retained.

Caveat on this rating: An exploratory re-analysis with no preregistered protocol, by authors who have argued elsewhere that fluoxetine's benefit in young people has shrunk over time. Fluoxetine still beat placebo beyond chance in every analysis; what changed is the size. The 2006 trial had not been retracted or corrected when the paper was written.

Caveat on this rating: One trial in veterans (84% men) who had already attempted, with modest lithium levels and a broad composite outcome; deaths were too few to compare. It tests adding lithium to usual care, not lithium started as the main treatment. The older meta-analysis of 48 smaller trials points the other way.

Caveat on this rating: Ever-use only, no dose; cannabis variants below genome-wide significance; pleiotropy tests possibly underpowered. Gage 2017 found a smaller cannabis effect and a stronger reverse direction.

Caveat on this rating: A methods critique: it argues effects are overstated but does not measure by how much, and it does not show the drugs have no effect. Read from the abstract only.

Caveat on this rating: Observational, no placebo, self-selected through psychedelic-friendly venues, 180 comparators against 953 microdosers; the app maker's staff and a supplement seller with patents on the tested combination are co-authors. Randomised trials find no clear effect.

Caveat on this rating: Small correlations, considerable heterogeneity, and a fail-safe number below criterion in every analysis; no link with live birth. The authors call the influence 'somewhat limited'. Boivin 2011 found no link. Read from the abstract only.

Caveat on this rating: Definitions do the heavy lifting here and are stated rather than assumed. 'Pregnancy-related' means causally related to the pregnancy and within one year of its end - a wider window than the 42-day definition used in international comparisons, which is why UK figures for suicide as a direct cause within 42 days (0.80 per 100,000) look nothing like the 6-week-to-1-year figures quoted. The MMRC category bundles suicide with overdose and poisoning related to substance use disorder, so it is not a suicide count. The 2020 US figure covers 38 states, not the nation, and a 2020 coding change moved substance-use-related overdose deaths into this category, which is part of why 22.5% is not comparable with the 11% from 2008-17. A separate CDC report gives 26% for mental health conditions as a CONTRIBUTING circumstance rather than an underlying cause; that figure answers a different question and is not used. None of these numbers say anything about the risk facing any individual reader.

Caveat on this rating: Every study in this row is observational and self-selected, and that cuts against the row's own direction as much as for it. Cohen 2006 recruited at three specialist perinatal psychiatry centres, so its population is women with severe recurrent illness rather than a general one, and its hazard ratio of 5.0 cannot be read as the causal effect of stopping. Grote 2010 measured antenatal depression rather than treatment status, and its effect sizes swing with the measurement instrument and the country. Jarde 2016's own conflict-of-interest subgroup nearly doubles the preterm-birth odds ratio, which is a warning about the literature and is printed here for that reason. No randomised trial of continuation versus discontinuation exists, so 'stopping is riskier' and 'continuing is riskier' rest on the same grade of evidence - which is the point of the stop, and why it closes on a conversation rather than a conclusion.

Caveat on this rating: What this row does not claim: that SSRIs in pregnancy are risk-free. Adjustment is not randomisation, and the propensity-score models can only correct for what was measured in claims data - smoking, alcohol, illness severity and body-mass index are poorly captured in Medicaid records, and residual confounding runs in both directions. The primary-PPHN result still clears one after adjustment. Brown 2017's sibling analysis has wide intervals rather than a null, and its authors wrote that a causal relationship cannot be ruled out. Sujan 2017's surviving preterm-birth association may itself reflect illness severity within a family rather than the drug. Levinson-Castiel is a single centre with 60 exposed infants. The defensible reading is that the large early relative risks shrank substantially under better designs, that the absolute excess risks are small where they persist, and that neither 'proven harmful' nor 'proven safe' is what the evidence supports.

Caveat on this rating: The uncertainty here is real and is printed rather than resolved. Patorno's adjusted risk ratio for cardiac malformations is 1.65 with a lower bound of 1.02, and the right ventricular outflow tract estimate is 2.66 with a lower bound of exactly 1.00 - both only just clear chance, and the lithium numerator for that outcome is suppressed under the Medicaid data-use agreement, so this row makes no claim about how many Ebstein cases the study did or did not observe. Patorno excluded Ebstein anomaly as a named outcome on purpose, because clinicians may be likelier to code a defect as Ebstein in an infant known to have been lithium-exposed. Munk-Olsen 2018's first-trimester malformation result is significant while its any-time and cardiac-specific results are not. Fornaro 2020's meta-analysis and Diav-Citrin 2014 point the same direction with wide intervals. The honest summary is a small absolute increase, dose-related, on a very small base - not the register's 400-fold, and not nothing.

Caveat on this rating: Named limits. EURAP is a prospective registry of women in epilepsy care, not a randomised comparison, and women prescribed valproate differ from women prescribed lamotrigine in ways registries cannot fully adjust away - the strongest single caution on every figure here. NEAD is observational and its age-6 arm retained 224 of 311 children. Christensen's whole-cohort autism estimate (4.42% vs 1.53%) is confounded by indication and the epilepsy-restricted hazard ratio of 1.7 (0.9-3.2) is NOT statistically significant; both are printed so the reader can see the difference the comparison group makes. The North American registry's 9.3% valproate figure is consistent with EURAP but its published abstract carries no confidence interval, so it is not quoted here. What is not in dispute across registries, cohorts and three regulators is the direction, the dose-dependence and the rough size.

Caveat on this rating: Recruited from a forum for people who believe they have PSSD, retrospective and self-reported; the authors state the design does not allow estimation of incidence. Only 23 of 532 met the strict criteria. Dose did not predict severity and depression did, so the illness remains part of the picture.

Caveat on this rating: Self-submitted reports to a website built to collect them, assembled by the website's founder. A case series describes; it cannot count incidence or establish causation in any case. The cross-class overlap is unexplained. No rate, mechanism or treatment.

Caveat on this rating: A narrative review that does not grade or count its sources. Seven proposed mechanisms and none established. The phototherapy 'promising results' rest on evidence the abstract does not describe. The review's purpose is partly to raise recognition, which is stated.

Caveat on this rating: The declarations of interest read literally: "KH has previously acted as a temporary consultant for Pfizer (manufacturers of sildenafil). MT has been paid to lecture and received travel expenses from Bristol-Myers Squibb (manufacturers of buspirone) and Otsuka; his spouse is an employee of GlaxoSmithKline (manufacturers of bupropion)." Two of the six authors therefore have financial ties to the makers of the two drugs the review endorses, which is why independence is scored false despite the funding being public. The reviewers also warn that partial reporting of subscale results in the source trials could bias the effect estimates upward.

Caveat on this rating: A regulatory label change is a precautionary act on a safety signal, not proof of incidence, causation, or permanence. The evidence base the PRAC weighed was EudraVigilance reports, literature, social media, and manufacturer reviews. Clomipramine and vortioxetine were part of the same signal assessment but were explicitly not covered by the labelling recommendation. US FDA labelling does not carry equivalent wording.

Caveat on this rating: The authors state that including open-label studies and pooling across different sexual-function scales "could reduce the significance of our findings," so the 25.8-80.3% band is wide partly because the source studies were not uniform. No funding statement or conflict-of-interest disclosure was accessible for this paper.

Caveat on this rating: Small to moderate effects over mostly short trials in clinical populations, with publication bias untestable; the review found no advantage over other active treatments. The published abstract and the authors' manuscript disagree on the participant and citation counts.

Caveat on this rating: A small effect (0.09 SD) in self-selected users paid to deactivate during an election; mood measured by daily texts did not move significantly. The companion Hunt trial is 143 students over three weeks.

Caveat on this rating: Observational cohort with self-reported symptoms dichotomised at a cutoff and imputed missing data; the authors' own hypothesis was that externality would predict psychotic experiences, not depression. The 1988 meta-analysis it sits beside could not be read and is cited without figures.

Caveat on this rating: Short laboratory experiments on momentary feeling by the originators of the theory being tested; sample sizes and funding not read. The effect includes lowered positive excitement, and only chosen solitude produced relaxation.

Caveat on this rating: Observational experience sampling in a self-selected 2010 iPhone sample; time-lag analyses suggest direction but cannot establish cause. The headline percentages are from Harvard's press release, not from paper text we could read.

Caveat on this rating: Scale-development work in mostly student samples; it distinguishes two traits and says nothing about whether reflection can be taught or whether it reduces distress. Scale details are relayed through a 2011 secondary source because the original full text was not readable.

Caveat on this rating: Read from the abstract and plain language summary only. Most included trials excluded young people at risk of suicide; suicide-related estimates are low certainty with wide intervals. The 2026 re-appraisal authors report that the full dataset behind this review was not retained.

Caveat on this rating: An exploratory re-analysis with no preregistered protocol, by authors who have argued elsewhere that fluoxetine's benefit in young people has shrunk over time. Fluoxetine still beat placebo beyond chance in every analysis; what changed is the size. The 2006 trial had not been retracted or corrected when the paper was written.

Caveat on this rating: One trial in veterans (84% men) who had already attempted, with modest lithium levels and a broad composite outcome; deaths were too few to compare. It tests adding lithium to usual care, not lithium started as the main treatment. The older meta-analysis of 48 smaller trials points the other way.

Caveat on this rating: Ever-use only, no dose; cannabis variants below genome-wide significance; pleiotropy tests possibly underpowered. Gage 2017 found a smaller cannabis effect and a stronger reverse direction.

Caveat on this rating: A methods critique: it argues effects are overstated but does not measure by how much, and it does not show the drugs have no effect. Read from the abstract only.

Caveat on this rating: Observational, no placebo, self-selected through psychedelic-friendly venues, 180 comparators against 953 microdosers; the app maker's staff and a supplement seller with patents on the tested combination are co-authors. Randomised trials find no clear effect.

Caveat on this rating: Treatment gap figures depend on survey instruments that define who counts as a case, and critics argue those instruments over-count distress as disorder, especially across cultures. The 2004 data are old and coverage has changed. The row uses the figure for what it measures, people meeting survey criteria who received no care, and does not claim all of them need medication.

Caveat on this rating: A debate paper, not a study, and twenty years old. The legal position in either country may have changed since; the row dates the claim to 2006. Supporters of advertising point to real under-treatment of depression and to evidence that adverts prompt some appropriate care. Both positions are printed in the same paper, and this row gives both.

Caveat on this rating: This is an argument paper by a single author, not a study with a comparison group. Sales can rise because unmet need is finally met, because of marketing, or both, and the paper cannot separate them. The stigma it describes was real, and campaigns that reduce stigma have defenders in public health. The row reports what the paper documents, the phrase and the sales, and does not claim the people treated were not ill.

Caveat on this rating: A systematic review of observational studies; the authors rate 21 of 36 included studies at serious risk of bias and note possible publication bias. Association across studies of many specialties and drug classes, not psychiatry specifically. The causal language is the authors' inference from timing and dose response, not a trial result.

Caveat on this rating: The alert describes patterns from enforcement cases and states that no single characteristic is determinative. It cites a trade-group position that speaker programs "help educate and inform other health care professionals about the benefits, risks, and appropriate uses of company medicines." Speaker programs are lawful when the facts and intent do not meet the statute; the alert does not name any company or clinician.

Caveat on this rating: A single reader classified the conclusions and a second reader would move some papers between groups. Payments made before a drug had a brand name are not attributed to it, which understates early money. A paper that names a drug is not always mainly about it. The analysis shows an association and a direction of conclusions; it cannot show that payment influenced any paper, and selection of successful investigators and publication bias are sufficient to produce much of the pattern.

Caveat on this rating: Correlational self-report surveys with broad screen-time items from 2007 to 2016; a small average can hide larger effects for some young people or uses. One author discloses unpaid advisory roles to Facebook and Google. The opposite reading of similar data (Twenge) remains contested.

Caveat on this rating: A meta-analysis of correlational studies led by authors who have long argued materialism is harmful; the pooled correlation is small and cause is not established in either direction.