Just to summarise. The JAMA review concluded that there was no significant withdrawal based on its main analysis (figure 2) of 11 studies, 10 of which involved people who took antidepressants for 8-12 weeks before stopping. (1/n) Longer term studies (ANTLER, Rosenbaum) were captured in the review but not analysed as part of this main analysis. The longest of the 11 studies went for 26 weeks but involved a drug (agomelatine) that no one thinks causes withdrawal (2/n)

The review by Kalfas on antidepressant withdrawal in JAMA Psychiatry will mislead as it is based largely on people who have taken antidepressants for 8-12 weeks in 11 RCTs-this will under-estimate the risks for millions of long-term users. Thread (1/n) bit.ly/4eFrZzO The main result is based on 11 randomised trials (picture). 6 go for 8 weeks, 4 go for 12 weeks and 1 for 26 weeks. The 26 week study and one of the 12 week studies involve agomelatine, a drug well known not to have much withdrawal effect. So mostly 8-12 week studies. 2/n

A new review of antidepressant withdrawal is coming out next week from Jauhar et al. Inevitably, it will include mostly short-term industry studies. Like a drunk looking under lamplight there will be little relevance to the millions of long-term users around the world. Thread 1/n The majority of published studies are short term studies conducted by the drug manufacturers. This is the same issue that beset the flawed Henssler review. 2/nbit.ly/4033836

The longer you take antidepressants the more severe and long-lasting withdrawal effects are and the harder they are to stop.

The same way that the longer a heavy object sits on mud the harder it is to get out: as we show in our new paper. Thread. (1/n) bit.ly/437yBTN In a survey of 310 people from NHS therapy services, most of whom said that antidepressants had been helpful to them, 80% reported withdrawal effects. 35% said withdrawal effects were mild, 30% said moderate and 15% said severe. (2/n)

We completed a systematic review and meta-analysis of antidepressant withdrawal effects and found that 43% of people experienced them, there was a trend towards longer exposure giving rise to a higher risk of withdrawal effects 1/nbit.ly/3YjQOLa This review was completed by the National Institute of Drug Dependence in China, Rather than focus on any study that mentioned withdrawal effects (e.g. chart reviews, known to underestimate) we focused on studies that quantified withdrawal effects 2/n

Review on antidepressant (AD) withdrawal in @lancetpsychiatry is misleading in several ways and and should not be seen as ‘gratifying’ as it underestimates the risk of withdrawal by focusing on short term industry trials 1/nbit.ly/3yQmSw9
bit.ly/4b5YELT It is somewhat informative for short term users of ADs because it covers patients who mostly used ADs for several weeks or months but not informative for long-term users who will have more common, severe, long-lasting withdrawal symptoms as shown elsewhere 2/n

For those who claim we are stigmatising them by saying that people with depression have broken brains – we are ofc saying the exact opposite that it does not take an abnormal brain to be depressed – you can do it just fine with a normal one!(1/6)bit.ly/3IbeI2x 70% of people by age 45 meet criteria for anxiety or depression
so this surely can’t be the sign of a ‘broken’/abnormal brain – much more likely to be a normal brain responding to +++ adversity as occurs to many of us at some point in our lives. (2/6)bit.ly/3I8zkbK

New article in CNS Drugs examining risk factors for antidepressant withdrawal. bit.ly/3FrFySr With @survivingADs @DavidTa23968240 @HengartnerMP Anders Sorensen (1/n) Longer duration of use associated with greater chance of withdrawal and more severe withdrawal based on re-analysis of individual patient data, longer use also possibly related to longer duration (but very little data). (2/n)

Our article on how to distinguish antidepressant withdrawal symptoms from relapse of an underlying condition is now free to access here: bit.ly/3Bcx0xY in @TheBJPsych Advances With @DavidTa23968240 BJPsych Podcast here: bit.ly/3RkFWXx (1/n) We explain some of the ways that withdrawal can be differentiated from relapse (specific symptoms, timing, response to re-instatement and also look at the evidence that withdrawal symptoms are mis-diagnosed as relapse in clinical trials (2/n)

I know I am well late to the party but just wanted to discuss the Stone analysis without jargon to show why a maths exercise can’t tell us more than a primary outcome from RCTs. And Stone can correct me if I am wrong. bmj.com/content/378/bm… (1/n) There are 10,000s of patients which are basically little dots arranged on a scale showing change in HAM-D score from baseline to end of study. Let’s take a person (dot) that has improved by 12 points in the study, treated with drug (2/n)

🧵Is depression caused by a chemical imbalance/low serotonin? We conducted a review of all the major areas of research on this topic go.nature.com/3IRwur7 (free open acccess) @HengartnerMP @joannamoncrieff @TomStockmann 1/n Why did we do this? 90% of the public believes that depression is caused by a chemical imbalance (amongst other reasons). bit.ly/3B4JXKE Doctors routinely tell patients that their depression is due a chemical problem in their brain, particularly low serotonin. 2/n

NICE has given its opinion for the 3rd time that esketamine (Spravato) should not be used in the NHS for depression for any group of patients bit.ly/3NMeAHx. Some of its reasons are worth outlining because they relate to many psych drugs 1/n In short it outlined that:
-the studies were too short (4 weeks) to extrapolate to actual clinical use
-unblinding by psychoactive effects would exaggerate the effectiveness of the drug (by expectations of improvement)

2/n

NICE's analysis of treatments for more severe depression- check out the SMD's on some of those bad boys! Bold means stat sig. Mindfulness, group problem solving, peer support - big effects, bigger than AD+CBT.nice.org.uk/guidance/GID-C… I should emphasise that is for MORE SEVERE depression - the new name for moderate to severe depression. The action on Sunday night is all at Evidence review B: nice.org.uk/guidance/GID-C…

The new NICE guidelines signal that singular attachment to antidepressants is increasingly anachronistic: bit.ly/3JK9gU3. Evidence for their benefit is poor, adverse effects myriad, lots of safer alternatives dtb.bmj.com/content/60/1/7 1/n

https://twitter.com/ReadReadj/status/1478813245741883407

As the comments from GPs in the article reveal the main barrier is access to alternatives which requires investment. Troubling to see that GPs consider ADs mere placebos. Personally I have no issue at all with pbos – I am not shouting down crystal healers 2/n

We were asked to write about balance of harms and benefits of antidepressants based on current knowledge for @DTB_BMJ, a BMJ journal that is famously independent and does not take pharma sponsorship/advertising bit.ly/3mnJXNn 1/n We know that physiological withdrawal effects make it hard for many people to stop antidepressants and for some it will simply be too difficult. RCPsych says people should know about severe and/or long-lasting withdrawal effects when considering starting 2/n

@joannamoncrieff and I reply to critics’ letters bit.ly/3wNOuwB regarding our analysis of esketamine bit.ly/3niISHH. There are now 6 short-terms studies published for esketamine vs pbo, 5 of which are negative, 1/8 and one which does not reach clinical significance from pbo.The FDA, which has shown itself not to have the distance from companies to make objective decision about #aducanumab, dropped the bar very low for Janssen on esketamine, re-writing the rules of what they would accept 2/8

David Taylor says this about the NEJM study: "This study shows that discontinuing antidepressants in long term users leads to a greater risk of relapse than that seen in people continuing their medication. It seems to suggest that antidepressants are effective at (1/n) preventing relapse. However, the speed and nature of antidepressant discontinuation is known to have a major effect on risk of relapse and this alone might explain the differences observed ..2/n

Startling lack of interest in confounding by withdrawal symptoms in this antidepressant discontinuation study in NEJM: bit.ly/3AYzP2Z Withdrawal symptoms in this discontinued group render this study uninterpretable. (1/n) Withdrawal symptoms in the discontinuation group would have inflated the apparent rate of relapse in this group (2/n)

Enjoyed the @rcpsych IC session on deprescribing with @wendyburn David Taylor and Robin Murray. We had over 100 questions put to us - not seen so many before. Some very good questions from psychiatrists: 'Why is not a requirement of licensing these drugs that they are shown...1/n to be safe to stop?'. 'Shouldn't we demand that manufacturers make medications in ways that make it easy to stop?' 'Why have academic psychopharmacologists, who should know best about this issue, both ignored and then minimised this problem?' 2/n

Outline of the Cochrane study a bit for those scared of its length. Metro article: bit.ly/3tVfOah Lead author: the dauntless Ellen van Leuween. Co-author @tony_kendrick bit.ly/32KLJhj While there are hundreds of studies looking at starting antidepressants(1/n) we found only 33 studies looking at stopping antidepressants, a therefore hugely neglected area 2/n

(Thread) Today we have published a paper on a way to reduce antipsychotics to minimise withdrawal effects and possibly relapse in @SchizBulletin. bit.ly/31bc8Eg with thanks to co-authors Robin Murray, David Taylor, @sameerjauhar and Sridhar Natesan. (1/n) It extends our work on risperidone to more antipsychotic drugs bit.ly/3tMFdSV
It provides some examples of pharmacologically rational tapering regimes for haloperidol, risperidone, olanzapine, clozapine, quetiapine and amisulpride which takes into account 2/n