The evidence library

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: Participants sourced and weighed their own material, so actual doses were unverified, and the sample was self-selected enthusiasts rather than people with a diagnosed condition. The authors are based at Imperial College's Centre for Psychedelic Research with a co-author from the Beckley Foundation, both proponents of psychedelic research — which cuts against, not toward, a bias explanation for this null result.

Caveat on this rating: Uncontrolled and unblinded: participants knew they were dosing, sourced their own substances, and were self-selected enthusiasts, so nothing here can separate drug effect from expectation. The authors say as much and explicitly call for dose- controlled research.

Caveat on this rating: Open-label by necessity (neither ketamine nor ECT can be masked), so subjective outcomes may favor the treatment patients preferred; population excluded psychotic depression, where ECT performs best.

Caveat on this rating: The racemic-vs-esketamine difference rests on indirect comparison across trials with different designs and populations; one coauthor (Zarate/NIMH) is an inventor on ketamine-related patents. An erratum was issued in 2021 (checked: not a retraction).

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: The high trust score reflects the review's method, funding, and journal, not the strength of the underlying trials: 398 men across 11 studies, several from the 1970s and 1980s, with waitlist controls and confidence intervals touching 1.0. The single trial claiming group therapy outperformed sildenafil alone (WMD -12.40 on the IIEF) had 20 participants and was run by one of the review's own authors, which is a direct conflict on the review's most eye-catching result.

Caveat on this rating: The high trust score reflects the quality of this meta-analysis as a piece of evidence synthesis, not the strength of the effect it found. The pooled benefit rests on a subjective, dichotomised outcome in six trials with demonstrated publication bias, and the authors' own conclusion is the hedged "valerian might improve sleep quality," followed by a call for better studies. Twenty years on, those studies have largely not materialised.

Caveat on this rating: This review reaches the opposite conclusion to Bent 2006 from overlapping trials, and the difference is instructive: Taibi weighted trial quality and recency, and found that the better and newer the study, the smaller the effect. That pattern is the signature of a treatment whose apparent benefit comes from weak methods.

Caveat on this rating: Dated: the search closed 31 December 2011 and the review has not been updated, so it predates the trauma-focused work of the last decade. Its conclusion applies to brief generic counselling as trialled up to 2011 and should not be read as evidence against structured psychological treatment for post-loss PTSD, depression, or complicated grief.

Caveat on this rating: These are screening-instrument prevalences drawn largely from cross-sectional studies with substantial heterogeneity, so they measure symptom burden rather than diagnosed disorder, and the pooled percentages are sensitive to which scales and cut-offs the contributing studies used.

Caveat on this rating: The control groups were not uniform — they mixed live births, difficult live births, and non-pregnant community samples — and "perinatal loss" spans early miscarriage through stillbirth, so the pooled risk ratios blur real differences between very different experiences.

Caveat on this rating: Only psychiatric conditions severe enough to require hospitalisation were captured, so ordinary depression and anxiety treated in primary care are invisible here — the absolute risks are small and the affective-disorder result should not be read as evidence that unsuccessful treatment protects against depression.

Caveat on this rating: The pregnancy-rate result is the weak half of this paper: the pooled studies were heterogeneous, not all randomised, and the finding directly contradicts the larger and better-controlled Boivin 2011 BMJ meta-analysis showing distress does not affect cycle outcome. Read this study as evidence that psychological support reduces distress, not as evidence that it makes you pregnant.

Caveat on this rating: Attrition was substantial and grew over follow-up: 67% of the loss cohort completed the one-month questionnaire, 58% at three months, and 46% at nine months, so the later percentages rest on a shrinking and possibly non-representative subgroup. These are validated screening thresholds, not clinical diagnoses.

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: The high trust score reflects the review's method, funding, and journal, not the strength of the underlying trials: 398 men across 11 studies, several from the 1970s and 1980s, with waitlist controls and confidence intervals touching 1.0. The single trial claiming group therapy outperformed sildenafil alone (WMD -12.40 on the IIEF) had 20 participants and was run by one of the review's own authors, which is a direct conflict on the review's most eye-catching result.

Caveat on this rating: Both arms improved similarly on the primary desire and arousal outcomes, so this trial does not show that mindfulness specifically works — it shows that eight weeks of structured group attention works. There was no no-treatment or waitlist arm, so regression to the mean and expectancy effects cannot be separated out. All 148 participants were cisgender women, and the authors note the need to diversify samples.

Caveat on this rating: Every pooled effect is against a waitlist, not an active or placebo control, so attention and expectancy are baked into the d = 0.58 figure. The search ends at 2009, predating the internet-delivered treatments that now dominate access. No total participant count is reported in the abstract, and the MEDLINE record lists the publication type "Research Support, Non-U.S. Gov't", indicating unnamed external support.