Our new meta-research paper out in the prestigious Journal of Clinical Epidemiology @JClinEpi with Martin Plöderl @PloederlM and Simone Amendola
Read it here:

Main findings summarized in thread belowjclinepi.com/article/S0895-… A while back we published a systematic review with meta-analysis on suicide risk with antidepressants in observational studies:

We were suprised to find substantial publication bias, thus we pre-registered a post-hoc analysis to examine furtherpubmed.ncbi.nlm.nih.gov/33685964/

Amidst the controversies surrounding our paper on the serotonin theory of depression, the FDA has published the largest and most comprehensive IPD analysis on the efficacy of antidepressants in the acute treatment of major depression. A brief summary:
bmj.com/content/378/bm… The average drug effect in adults was a modest d=0.24, whereas in children and adolescents it was a meagre d=0.13 (thus close to zero)
The were some notable differences between drugs.

This is hillarious. In a recent Nature paper, Dr. Nutt, with co-authors, writes:
"even the best-performing antidepressant drugs show modest efficacy, non-negligible side effects, discontinuation problems and high relapse rates, highlighting the need for new, improved treatments" A few years ago Dr Nutt contended that antidepressants "have an impressive effect size in the treatment of acute cases of depression" and "antidepressants have an impressive ability to prevent recurrence of depression ... which makes them one of the most effective of all drugs"

Lots of interesting data in this study on antidepressant use in Australia 2015-2019. A short summary:

pubmed.ncbi.nlm.nih.gov/35176912/ Overall prevalence of AD use increased 7.0% in females and 9.2% in males. In 2019, 17% of women and 10% of men used AD
Prevalence increased mostly in younger age groups, ie in 10-17y olds (27% and 34% increase in w and m, respectively) and in 18-24y olds (17% and 16% increase)

I really like this impressive study. Across a broad range of neurobiological and genetic measures, and using a very large sample and standardised protocols, there are almost no differences between people with and without depression. Very important study:
arxiv.org/pdf/2112.10730… As stressed by the authors:
"Even when considering the upper bound of the deviation in each modality, none could be considered informative from a personalized psychiatry perspective with both groups being nearly indistinguishable on a single-subject level."

Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 thelancet.com/journals/lanps… Authors write:

„To reduce the burden of mental disorders, coordinated delivery of effective prevention and treatment programmes by governments and the global health community is imperative“

Currently many people interpret the results of this short-term study on suicide rates (2004-2018) in Scottland as evidence that antidepressants mitigate suicide risk on the population level. These conclusions don't hold for various reasons. A thread:
cambridge.org/core/journals/… First, ecological studies cannot prove causal associations. Be aware of the ecological fallacy. On a group level you may find a spurious correlation between exposure variable and outcome that is simply not there on the individual level:

pubmed.ncbi.nlm.nih.gov/2656561/

Results of the ANTLER trial on the outcome of antidepressant maintenance treatment are finally published. In sum, findings were mixed overall and left me with many questions. A short thread:

nejm.org/doi/full/10.10… The good news first: at 52 weeks patients maintained on antidepressants had less relapses than patients who discontinued (39% vs 56%). Rate of serious adverse events was low and did not differ between groups

Important study that estimates the minimal clinically important difference (clinical significance) in antidepressant trials. As assessed with PHQ-9, a clinically significant effect should be larger than 2 points or a standardized mean difference of >0.5.
pubmed.ncbi.nlm.nih.gov/33892086/ Quote from the authors:
"The mean difference method, applied in the less severe PANDA sample, suggests an MCID of ˜2 points or a SMD ˜0.5–0.6, which is comparable to previous re- search"

Essential reading. Bioindustry largely setting the medical research agendy. Of course biased towards their commercial interests:

journals.plos.org/plosone/articl… „Overall, the main focus of the prevailing HBMS agenda appears to be set on therapeutic and specifically pharmacological intervention involving the use of novel drugs or innovative molecular biology techniques.“

Our meta-analysis of the suicide risk associated with antidepressants in case-control and cohort studies of adults with depression and other common treatment indications is finally published in the Journal of Epidemiology and Community Health:
jech.bmj.com/content/early/… The paper is behind paywall, but you can access the preprint for free here:
medrxiv.org/content/10.110…
You also find the raw data, the preregistered protocol and all statistical code on the Open Science Framework:
osf.io/eaqwn/

Our systematic review and meta-analysis of observational studies on the suicide risk with antidepressants in adults is now available as a preprint:
medrxiv.org/content/10.110…
Thanks to the collaborators, Mr Amendola, Prof Bschor, Ms Kindler, @JakobKaminski and @Martin_Ploederl In total 27 cohort and case-control studies with adult patients met our inclusion criteria and were quantitatively synthesized. All analyses pre-specified in the protocol showed either no definite association or significantly increased suicide risk with antidepressants.

I am still a bit puzzled, how fiercly some psychiatrists debated the conclusion of my recent paper, that in depression relapse prevention trials preventive effects and withdrawal effects are severely confounded. So I checked various relapse prevention trials for anxiety disorders Consistent with excess risk in the first few weeks and no preventive effects after 12 weeks in depression trials, I found exactly the same pattern in discontinuation trials for anxiety disorders. That is, drug-placebo separation only at the beginning; no preventive effects later

In my new open access paper, I critically discuss whether long-term antidepressant use has prophylactic effects, ie., whether long-term use effectively protects against depression relapses and why we must consider withdrawal reactions. Short thread:

journals.sagepub.com/doi/full/10.11… Evidence of antidepressants' prophylactic effects almost exclusively relies on relapse prevention (discontinuation) trials where patients in remission are randomised to either have their antidepressant abruptly stopped and replaced by inert placebo or to continue active treatment

New important and well-designed paper by Maruo et al that complements our recent work on treatment heterogeneity in antidepressant trials. What is the scope for personalized (precision) medicine in depression? sciencedirect.com/science/articl… As the authors point out right at the beginning of their paper: "Precision medicine or personalized medicine in depression has been much discussed but has seen little success so far". Put differently: Expectations and promises are huge, but thus far the output is poor.

1/n
Hayes et al published a critique of my recent paper with @Martin_Ploederl on the suicide risk with antidepressants. Thus, we address issues that were not covered in our original paper due to space limitations and firm opposition from one reviewer karger.com/Article/FullTe… 2/n
So where do Hayes et al find fault with our paper? Their main point is that we should have used a meta-analytic method. This is a legitimate critique. We simply didn't use such a method because previous analyses of the FDA database did not use such methods either.

When I state that the mean antidepressant-placebo difference is just 2 points on the Hamilton depression scale (e.g. ncbi.nlm.nih.gov/pmc/articles/P…), many mental health professionals reply that response rates are more informative. In fact, the opposite is true, so let me explain: 1
Many professionals agree that the difference on the Hamilton scale is indeed unimpressive, but they swiftly add that the difference in response rates would be substantial and relevant. Alarmingly, even drug regulators fall for this logical fallacy (ncbi.nlm.nih.gov/pubmed/18621509).

There are so many misrepresentations in this new commentary by Goodwin and Nutt about the efficacy of antidepressants… I don't know where to start. So here are just 3 examples of misleading statements in this paper (thread): cambridge.org/core/journals/… First misleading claim by Goodwin & Nutt: “The number needed to treat (NNT) in studies with a mean drug–placebo difference on the HDRS scale of around 3 is between 5 and 7…”

Obviously Jauhar and Hayes do not want to end the „war on antidepressants“, as now they even made text changes to the published version of their critique of the withdrawal review to defend their misleading statements. So, sadly enough, the debate has to continue… Thread 1/n
Here the critique they originally published: "[Davies & Read] seem also to misunderstand simple principles that underpin why blinded RCTs are necessary. Thus, in the trial by Montgomery et al. (2005), DESS score was higher during placebo treatment than active treatment.”