Most recently updated on 10 January, 2024
Hello! This is the questions, clarifications and corrections section of the Lost Connections website. As with my previous book ‘Chasing The Scream’, I’m really keen to make sure I have been entirely accurate, and I went through a detailed fact-checking and editing process. Once a month I’ll post an update here, and have any errors corrected for future editions. (You can see the corrections page for Chasing The Scream here to get a sense of what I’m talking about.)
I’m also very happy to have an open conversation about areas where some people think I have made an error and I consult the facts and disagree.
I was emailed and asked to respond to a few people’s queries and comments about the book.
A RESPONSE TO DEAN BURNETT
A curious thing happened when my book Lost Connections came out. I realised that when you write a book that gets discussed by lots of people, in fact two books are created at the same time. The first is your actual physical book – containing the words you wrote – which goes out into the world and gets read. The second is a kind of shadow-book that, at the same time, is created on social media. This shadow-book consists of all the things that people who haven’t read your book imagine that it says. This shadow-book isn’t written by you, the author; it is written by people on social media – and it often bears little relationship to your actual book.
With Lost Connections, the shadow-book was largely created by a blogger called Dean Burnett, who wrote an article angrily denouncing the book on the day it came out, and another one a few weeks later. To his credit, he admitted in the first piece he hadn’t read my book – but he nonetheless made a series of claims about what it says. (He later admitted on social media he hadn’t read it when he wrote the second piece either).
All the other people I am responding to in this section of my site – where I engage with requests for corrections – have raised serious scientific questions in a spirit of serious scientific debate, which I welcome. With Dean Burnett, the situation is slightly different: he has made a series of eight claims about what I write in my book that are clearly false.
Of course, you’d expect somebody to make lots of mistakes about a book if he writes repeatedly about it without reading it – and that is what has happened here. What I’d like to do – though it might be a slightly boring read (the book is better, I promise!) – is disentangle my actual book from the shadow-book created by Burnett, by going through his eight serious errors.
It’s worth letting readers know at the start that about a month after these incorrect claims were made, the website where he and I have both written – the Guardian – took the unusual step of issuing a clarification at the end of Burnett’s pieces. They pointed out that the core charge he makes – that I am trying to get people to abruptly quit anti-depressants – is not what I say, nor is it what I believe. My actual book recommends that the people helped by chemical anti-depressants continue to take them (as I did for many years).
I’d like to go through his claims one by one.
Claim one: He says I claim that only one kind of treatment is available on the British National Health Service for depression, when in fact there are many.
Response one: There’s a whole chapter in the book about different treatments available through the NHS – the people who run these programs are some of the heroes of the book (It’s chapter seventeen for anyone who wants to check it out).
Claim two: Burnett argues I present some of my wider arguments – that there are deeper social and psychological causes of depression and anxiety which must be dealt with – as if they are new, when in fact they are mainstream and well-known within the scientific community.
Response two: My book is full of the stories of the mainstream scientists who discovered these causes of depression and anxiety. It’s the main meat of ‘Lost Connections.’
Burnett seems to be basing his criticisms on a short article I wrote for the Guardian, explaining a handful of themes in ‘Lost Connections,’ and a short interview I did with them. But even in the material Burnett claims to have read, I explain that these facts and arguments are well-known and mainstream in the field, writing: “This is radical, but it is not, I discovered, some maverick position. In its official statement for World Health Day in 2017, the United Nations reviewed the best evidence and concluded that “the dominant biomedical narrative of depression” is based on “biased and selective use of research outcomes” that “must be abandoned.””
So for Burnett to claim I am saying I discovered these claims by myself is not correct, when I explicitly attribute them to the most mainstream medical body on the planet, the World Health Organisation, and to the dozens of scientists I write about.
My point is (as I say repeatedly in the book) not that these arguments are new to psychiatrists and researchers: they already know them. My argument is that they are too often new to the general public, who have very rarely been told about them, and to the wider culture, which has not built a better system based on these insights.
Claim three: He says many of these insights have been known since the 1970s.
Response three: That’s correct – which is why the book is full of the stories of the scientists who discovered these insights in the 1970s.
This sadly makes me conclude that, in addition to not reading the book, he has also not even read the short extract he claims to be critiquing – since in that extract, I explain that Professor Michael Marmot made his discovery about the circumstances in which work causes depression in the 1970s.
Claim four: Burnett wrote an article imploring people not to quit their anti-depressants overnight in response to my book. He admits two-thirds of the way in that I have never said they should, but he clearly insinuates this is somehow my position anyway.
Response four: It is false to suggest I have ever implied to anyone that they should ever stop taking chemical anti-depressants. On page 37 of the book, speaking of these drugs, I say to people taking these drugs: “If you feel helped by them, and the positives outweigh the side effects, you should carry on.” Some of the people I most love take chemical anti-depressants, and I have never once urged them to stop.
I explain in the book, and in my interviews about it, that anti-depressants gave me a real boost when I initially took them, and that they have a real benefit for some people. For the people who are experiencing benefits on them that outweigh the side-effects, I offer only love and encouragement – as my book makes clear. I want to expand the menu of options for depressed people – not take anything off the menu. I have also explained that if people for whom they are not working decide to stop, I would in the strongest possible terms urge them never to stop abruptly, but instead to do what I did: cut back very slowly, under the supervision of their GP, over a period of six months. The book warns that 20 percent of people who stop experience severe withdrawal symptoms – a clear reason, if you’re going to stop at all, to stop very slowly.
(Burnett presents the risk of withdrawal symptoms as if it were an argument against ‘Lost Connections’ – when, in fact, the book clearly warns about the serious risk of withdrawal.)
I also make the case that we need to have a nuanced debate about chemical anti-depressants. It’s a fact we have to face that the long-term research into chemical anti-depressants – the Star-D trial – shows that most people taking them become depressed again over the long term. This doesn’t mean the drugs have no value – they help some people, which is brilliant – but they are (alas) not solving the problem for most of us. It’s also a fact that for more than thirty years now, we have rapidly expanded prescriptions of anti-depressants, and in each one of those years, depression has continued to rise. There’s something missing in this picture. We need to have a broader series of explanations for why this epidemic is happening, and a broader menu of solutions. My book is about what those causes of depression are, and the evidence being discovered all over the world about the solutions.
I am puzzled about why Burnett is reacting this way to my wider point about anti-depressants since Burnett himself made exactly this argument less than a year before he attacked me for making it. In an article, he stated: “It’s not surprising, then, that antidepressants don’t work, or even make things worse, for many patients.” As proof for the accuracy of his claim, he approvingly linked to a study entitled ‘Why Anti-Depressants Don’t Work For So Many’, of which the subtitle is: “More than half the people who take anti-depressants for depression never get relief.”
So when it comes to my work, Burnett claims that pointing out any partial limitations to chemical anti-depressants is tantamount to urging everyone to abruptly discard them. Using this logic, I could just as easily write a piece implying Dean Burnett is telling people to stop taking their anti-depressants overnight and condemning him for putting people in danger.
It would be obviously wrong to say this about Burnett; and his attempt to imply that about me is equally wrong.
Claim five: Burnett claims what I say about the grief exception in this article is inaccurate.
To explain the context for this: In the 1970s, the American Psychiatric Association (APA) decided – for the first time – to draw up a clear definition of depression and send it out to all psychiatrists in the US. They laid out ten symptoms (like crying a lot, or feeling incapable of pleasure), and they said if any patient shows more than six of these symptoms for more than two weeks, they should be diagnosed as mentally ill. So psychiatrists started to use this checklist – but after a few months, they came back and said, in effect: we’ve got a problem here. If we use this checklist in the way you’ve said, we are going to have to diagnose every grieving person in the US as mentally ill – because when you lose somebody you love, you naturally feel this way.
The APA explained that isn’t what they intended. So they got together and announced they had created something called “the grief exception.” They said to psychiatrists – if any patient shows more than six of these symptoms for more than two weeks, diagnose them as mentally ill, unless they have lost somebody they love in the past year. If they have, they’re not mentally ill; it’s a normal response.
So psychiatrists started doing this – but this led people to ask some awkward questions. How can we tell patients that depression is just a biological problem in their brains, except in one unique situation, where it’s actually a reasonable response to life? Why is losing somebody you love the only situation where it’s reasonable? Why not if – say – you were raped as a child? Or your parents didn’t love you? Or you are terribly lonely? Or you are humiliated at work?
So the APA got rid of the grief exception. I point out in one of the articles based on the book that now, if your child dies, you can be diagnosed almost immediately with depression – and this is, in fact, happening to many parents.
Burnett argues this is inaccurate, since the rules say you have to have been showing the symptoms for two weeks. How then, he asks, can the parents be diagnosed immediately? The most you can say is that they will be diagnosed after two weeks.
Response five: The leading expert on the grief exception in the world, Dr Joanne Caciatorre, has responded to Burnett, presenting scientific evidence that the circumstances he claims cannot happen – immediate diagnosis of a grieving parent – in fact happen often.
In many cases of diagnosis of depression, doctors ask the patient a variant of the question: “Have you felt this way over the past two weeks?” and they run through the symptom list. It is a retrospective diagnosis. So rather than tracking the parent over time, they often ask the patient to remember their own feelings and give an immediate diagnosis. The symptoms of depression are not uncommon in mothers in the last few weeks of pregnancy. Many women in this situation, asked if they recall feeling this way, will say yes. So the doctor doesn’t have to wait, as Burnett claims. (Of course many doctors do wait – but it is not required).
Dr Caciatorre conducted detailed research into this and showed that – far from it being impossible, as Burnett claims – rapid diagnosis and drugging of grieving parents is happening frequently: 9 percent of grieving parents are drugged in the first 48 hours (Lacasse & Cacciatore, 2014). If Burnett has evidence that the leading expert in the world and her published record of scientific research on this is incorrect, he should offer it. He has been aware of this scientific study showing what he said is factually inaccurate for a year now, and to my knowledge he has neither presented any counter-veiling evidence that what he said is correct, nor retracted his claim.
Claim six: He says that Professor Irving Kirsch of Harvard Medical School is a marginal figure in the field and his findings on anti-depressants should not be taken seriously.
Response six: As I pointed out above, and it bears repeating: Burnett himself has written approvingly about, and linked to scientific reports by, scientists who are just as critical as Irving Kirsch’s, and he drew the same point from the research. Burnett wrote last year: “It’s not surprising, then, that antidepressants don’t work, or even make things worse, for many patients.” As proof for the accuracy of his claim, he linked to a study entitled ‘Why Anti-Depressants Don’t Work For So Many’, of which the subtitle is: “More than half the people who take anti-depressants for depression never get relief.”
This is a large part of Kirsch’s point, and my point. Some people get relief from chemical anti-depressants: they deserve only love and encouragement. But we also need a much wider debate, because there are many people they don’t help – and many of the people who are helped receive only temporary relief. I am puzzled about why Burnett is so outraged by a Harvard professor (one of the leading experts in the world on this) and I pointing out the same facts he pointed out himself less than a year ago.
If Burnett is saying Professor Kirsch’s position is marginal and should be dismissed, he is also saying his own position, expressed just a year before, is also marginal and should be dismissed. As it happens, both Burnett (in his earlier incarnation) and Kirsch are broadly right – and making a point we need, as a culture, to deal with.
Claim seven: Burnett claims that I have “cherry-picked” studies that find what I wanted to see, rather than dispassionately surveying the evidence.
Response seven: For more than a decade, I wrote articles and gave interviews defending the idea that depression is caused by a chemical imbalance and saying that the primary and most important response was to give people chemical anti-depressants. I believed it passionately. It was a core part of how I saw the world. If I was “cherry-picking” studies that confirmed what I already thought, I would have looked for studies that reinforced this belief.
In fact, what I did was the opposite of cherry-picking: I was ultimately persuaded by evidence that went against what I wanted to believe. I learned that depression is not caused by a simple “chemical imbalance” (although there are real biological causes alongside psychological and social causes). I learned that chemical anti-depressants have a real but limited effect, and we need a much broader response. I explain all this very clearly in the book. I also go through the reasons why I was persuaded by the particular trials I cite, especially the Star-D trial: because it is the study that most closely resembles how people are using chemical anti-depressants in the real world, for reasons detailed at length in the book.
Claim eight: Burnett argues that my book is somehow an attack on doctors and psychiatrists who are working hard and doing their best.
Response eight: Far from being opposed to psychiatry, I am hugely sympathetic to doctors and psychiatrists working day to day with some of the most distressed people in our culture, who – as the book explains – overwhelmingly work really hard to do the best for their patients. They are doing their best with the tools they are given. My own sister was, until very recently, a psychiatric nurse, and I am enormously proud of her and the work she did, which saved lives.
It is the wider society – all the rest of us – that need to do a better job of giving them better tools, of acting on the insights from the best research into mental health, and (most importantly of all) of changing the way we all live so that fewer people are left in a state of profound distress.
We don’t leave the job of dealing with car crashes simply to people who have already been mangled in car accidents and to doctors in emergency rooms. We know that the culture has to change to prevent it – through airbags and seatbelts and speed limits and bans on drunk-driving. We need a comparable cultural shift to deal with the nine deep causes of depression and anxiety I was able to find evidence for in ‘Lost Connections.’ I think people can see it is a deep misunderstanding to think that making this case is an attack on psychiatrists, any more than making the case for airbags is an attack on doctors doing the night-shift in the Emergency Room.
Unlike Burnett, there are two journalists at the Guardian who have in fact read my book. One is their Readers Editor, Paul Chadwick, who – as I mentioned before – has taken the unusual step of issuing a clarification at the end of both Burnett’s blog posts, linking to the series of corrections you are reading now. Chadwick points out that I do not urge people to abruptly stop taking chemical anti-depressants – which runs contrary to the headline and substance of Burnett’s posts.
The other Guardian writer who read my book – for their lead review of it – praises the book’s scientific and factual rigour, gives an accurate summary of the book that bears no relationship to Burnett’s, and strongly recommends people read it. She reviewed the book, not the shadow-book. You can read that review here.
Depressed and anxious people deserve a serious debate about the causes of depression and anxiety, not a series of straw men and fictitious claims. I am puzzled about why Burnett – who’s usually a good writer – would write twice about a book he hasn’t read, and refuse to correct himself when he is shown clear evidence that the shadow-book he created in his mind bears very little resemblance to my actual book. He does mention repeatedly that he regards himself as having written a “rival book” which he seems to regard my book as detracting attention or sales from. In the middle of a depression and anxiety crisis, we need as many books engaging with the deeper causes as we can, and I wish his book well.
We all get things wrong some times – god knows, I have. Writing lengthy attacks on a book you have never read is obviously an error.
I feel confident that, in time, when he reflects on all this with a cool head and picks up a copy of ‘Lost Connections’, Burnett – who has written articles I admire, and is not a bad person – will see that he has screwed up here, as we all do sometimes, and will correct the factual mistakes he made.
(PS I was inspired to think of the concept of a “shadow-book” by this excellent piece by Helen Andrews).
CORRECTION TO PAGE 134
On page 134, I say: “By 2016, this became a front-page issue in Canada when in a single reservation on a single night, eleven First Nations people killed themselves.”
Jessica Ankomah emailed to point out that in fact on that day eleven First Nations people attempted to kill themselves, and she’s right.
This will be corrected in all future editions and I’m grateful to Jessica for drawing my attention to this error.
In addition, I was emailed by Marylu McGrath about a related matter. First Nations children in Canada were kidnapped from their parents for decades and raised apart from them in brutal conditions. I refer to the places they were taken to as “boarding schools.” Marylu pointed out to me that First Nations people regard this as an offensive term, and call them instead “residential schools”. After consulting on this I learned she is right and so this will also be corrected in future editions. Thank you to Marylu for informing me of this.
A RESPONSE TO DR CARMINE PARIANTE
Dr Carmine Pariante wrote an article in the Independent entitled ‘As a psychiatrist, I know Johann Hari is wrong to cast doubt on anti-depressants’. Dr Pariante and I concur on a lot, and I admire his work. He wrote to me: “As a psychiatrist, I value your emphasis on the importance of social connections, and I hope that you will recognize in my response the many points on which I completely agree with you.”
We differ a little on some questions (not all) surrounding chemical anti-depressants. I want to go through his two key points separately:
Point one: Dr Pariante argues: “Antidepressants reverse some of the physical effects of depression: increasing production of new brain cells, and reducing inflammation.”
Response: I asked him to send me the study on which he was basing this conclusion, and I looked at it carefully and then asked Professor Kirsch for his analysis. (Again, I had discussed this question during my research with several scientists, but I wanted to return to it here with one of the most distinguished figures in the field to make sure I had understood it.) The study Dr Pariante sent over is here.
Professor Kirsch responded: “Pariante bases this conclusion on an uncontrolled study. With no control group, there is no way of knowing whether the effect was due to the antidepressant, rather than it being a consequence of improvement in depression brought about by the passage of time and/or the placebo effect. For example, using PET, Mayberg and colleagues found that successful treatment with an SSRI was associated with “metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus.” The hitch is that pretty much the same changes were observed among participants who had been successfully treated with placebo.”
Point two: Dr Pariante also argued: “Studies using the most rigorous approaches (supported by publicly funded bodies, such as the Medical Research Council, not just pharmaceutical companies as Hari suggests) show that antidepressants lift the pervasive sadness at the core of clinical depression, albeit with varying effects on other symptoms such as sleep or appetite problems.” (The study he sent me for this is here)
I respond to the argument about publicly-funded trials later – see below.
Concerning the argument that chemical anti-depressants lift the pervasive sadness at the heart of depression, Professor Kirsch responded: “Pariante bases this on a recent study by Hieronymus et al (2017) in which superiority of SSRI over placebo were found more consistently on a single item of the Hamilton depression scale than on the total score of the scale. There is a reason for constructing scales made of many items, and the reason is that multi-item scales are more reliable that single items in that scale. For example, in the supplementary material of the Hieronymus study, it was revealed that side effects were associated higher single-item depression scores on one of the two SSRIs studied (citalopram) but lower scores the other (paroxetine). Further, the single item on which these findings were based does not measure “the pervasive sadness at the core of clinical depression.” Here is what that the item actually says:
1 DEPRESSED MOOD (sadness, hopeless, helpless, worthless)
0 |__| Absent.
1 |__| These feeling states indicated only on questioning.
2 |__| These feeling states spontaneously reported verbally.
3 |__| Communicates feeling states non-verbally, i.e. through facial expression, posture, voice and tendency to weep.
4 |__| Patient reports virtually only these feeling states in his/her spontaneous verbal and non-verbal communication.
The mean score on this item was between 1 and 2, regardless of whether patients were given drug or placebo, meaning that both groups reported feeling sad, hopeless, helpless, and worthless after treatment, but those who had been given the SSRI were more likely to state them without being asked and those given placebo more likely to wait to be asked. Now I ask you, is this a clinically meaningful difference in outcome?”
I found these arguments by Professor Kirsch persuasive but this is an on-going scientific argument in which they are both far more expert than me, and I’m looking forward to continuing to follow it.
I’m grateful to Dr Cariante and to Professor Kirsch – who agree on a lot – for engaging in this way.
RESPONSE TO STUART RITCHIE
On Twitter, an academic named Stuart Ritchie from the University of Edinburgh queried the section in the book where I write that “between 65 and 80% of people on antidepressants are depressed again within a year.” He argued that in fact the figure was four times lower.
I initially learned this statistic in a book by Dr Steve Ilardi, Associate Professor at Clinical Psychology at the University of Kansas, ‘The Depression Cure’ (see pages 44 to 45), which is in the book’s endnotes. As part of the process of researching my book and deciding whether to include it, I read through the studies Dr Ilardi cites, and discussed in depth this field of research with Professor Irving Kirsch, Professor John Ioannidis (a scientist who Ritchie praises strongly), Professor Joanna Moncrieff, Dr David Healey, Dr Lucy Johnson, Dr Sam Everington, Dr Vincent Felitti, Professor Michael Chandler, and with people who defend anti-depressants more strongly like Dr Peter Kramer, and read many relevant scientific papers on the topic.
The main evidence for this figure is a major and much-discussed study named the Star*D trial. In my book, I explain in detail why I was persuaded by the people I interviewed and by my reading of the evidence that the results from the Star*D trial are the most reliable evidence we have about the long-term efficacy of chemical anti-depressants.
It is what is known as a long-term naturalistic study. This means the scientists carrying it out follow ordinary people who seek medical help for being depressed, and tracks them over the long-term to see if the treatment they receive helps them and whether the positive effects last. This is the scientific method closest to the real-world experience of people who experience depression and receive help for it. It is different to clinical trials, which are most more restricted, and therefore less close to ordinary experience. For example, one study has estimated that 77% of the patients included in the Star*D trial would have been excluded from a normal clinical trial. See: Wisniewski SR, Rush AJ, Nierenberg AA, et al.. Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR*D report. Am J Psychiatry 2009;166:599–607. 10.1176/appi.ajp.2008.08071027
In the Star*D trial, as its actors explain, over 2,000 patients completed Step 1 treatment with an SSRI anti-depressant. About 30% achieved remission – i.e. they ceased being depressed. If they did not, they were offered the chance to progress to more aggressive treatment levels. Remission became less and less likely as the harder depression was to treat – by Step 4 only 7-16% of patients achieved remission (depending on the particular treatment option offered at this stage). However overall, the rate of remission from initial treatment was 67%, as I state in my book. Those who responded were followed up for 12 months. They continued to receive free clinical treatment. Nevertheless a substantial proportion dropped out – including more than 20% of the Step 1 participants and more than 40% of those who had made it to Step 3. At the end of 12 months’ follow-up, more than 50% of the Step 1 participants, nearly 75% of the Step 2 and about 80% of the Step 3 participants had relapsed (i.e. had become depressed again). See figure 2 in this paper, which I cite in the book (end-note 45): Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. doi:10.1176/ajp.2006.163.11.1905
After carefully considering the arguments and evidence presented here and in other studies, and after discussing it in detail with leading experts, I was persuaded by Dr Ilardi’s description of the situation: that the recovery rate from depression for people using SSRIs is between 20 and 35%, i.e. somewhere between 80 and 65% of patients either do not recover with this medication, or recover but then become depressed again within a year.
Other studies I drew on for this and which are footnoted in the book include: Diane Warden et al., “The STAR*D Project Results: A Comprehensive Review of Findings,” Current Psychiatry Reports 9, no. 6 (2007): 449–459; A. John Rush et al., “Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report,” American Journal of Psychiatry 163 (2006) : 1905–1917; Bradley Gaynes et al., “What Did STAR*D Teach Us? Results from a Large-Scale, Practical, Clinical Trial for Patients With Depression,” Psychiatric Services 60, no. 11 (November 2009), http://dx.doi.org/10.1176/ps.2009.60.11.1439; Mark Sinyor et al., “The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Trial: A Review,” Canadian Journal of Psychiatry 55, no. 3 (March 2010): 126–135, doi: 10.1177/070674371005500303 ; Thomas Insel at al., “The STAR*D Trial: Revealing the Need for Better Treatments” Psychiatric Services 60 (2009): 1466–1467 . Warden et al., “The STAR*D project results: A comprehensive review of findings,” Current Psychiatry Reports 9, no. 6 (Dec. 2007): 449–459. (Not every one of these studies is in agreement, of course.)
In the book I clearly reflect countervailing views, including people who think these drugs are more effective than Dr Illardi concluded, and people who think these drugs are less effective than Dr Illardi concluded.
Against this, Stuart Ritchie put forward four studies which he asked me to consider, which are the source of his claim that the drugs are in fact three to four times more effective than I argued in ‘Lost Connections’:
“This 2003 meta-analysis of 31 studies found a 1-year relapse rate of 19% with antidepressants (vs. 41% with placebo): https://www.ncbi.nlm.nih.gov/pubmed/12606176
This 2008 meta-analysis of 23 studies found a 1-year relapse rate of ~20% with antidepressants (vs. ~40% with placebo – see Figure 3): https://t.co/V8TawlMS1E
This 2009 meta-analysis of 11 studies found a 1-year relapse rate of 23% with antidepressants (vs. 51% with placebo): http://onlinelibrary.wiley.com/doi/10.1002/hup.1033/full
This 2016 meta-analysis of 72 brief studies (~8 months) found a relapse rate of 23.3% with antidepressants (49.4% w/discontinuation); and of 37 longer studies (~2yrs) found a relapse rate of 24.5% (vs. 55.6% w/placebo): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772815/”
As discussed above, these are clinical trials, and I am more persuaded by the evidence from the Star*D trial, which was far closer to the real world situation faced by my readers. The issues with relying on evidence from clinical trials and disregarding evidence from naturalistic studies have been widely discussed. Professor Irving Kirsch at Harvard Medical School recently outlined some of the many issues with available evidence from SSRI clinical trials specifically (such as those Ritchie’s meta-analyses draw on) in this 2020 paper, and I recommend reading it in full: Jakobsen JC, Gluud C, Kirsch I. Should antidepressants be used for major depressive disorder?.BMJ Evid Based Med. 2020;25(4):130. doi:10.1136/bmjebm-2019-111238
Since the book was published, further evidence has been gathered by scientists suggesting the judgement call I made on this evidence was correct: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558880/#
Mr Ritchie’s position on this is nonetheless worth engaging with, and while there are many scientists who agree with the conclusion I have reached, there are many there scientists who agree with the conclusion he has reached, and this is – as I reflect in the book – a legitimate on-going scientific debate with reasonable people on both sides.
(Note: This response to Stuart Ritchie was updated and amended on January 10th 2024 to add some additional material)
RESPONSE TO ZOE STAVRI
Zoe Stavri argues that I am wrong to draw on the work of Professor Irving Kirsch, for three reasons. I was aware during my research of these criticisms (not specifically from Stavri, but from others), and I was also aware of Professor Kirsch’s response to them, and I was broadly persuaded by Professor Kirsch’s arguments. I asked him to reiterate them specifically for this page.
Point one, from Stavri. She says: ‘Kirsch and colleagues didn’t find that antidepressants don’t work on the majority of people: they found that effectiveness of antidepressants are more effective for severe depression and less effective for mild or moderate depression. That’s a nuanced difference’
Response, from Professor Kirsch (the square brackets are from me): “We found no drug-placebo effect at all for mild or moderate depression and less than clinically significant differences for most people with very severe depression. Those who are depressed enough to show a clinically (as opposed to statistically) significant difference represent approximately 10% of patients presenting in practice with diagnoses of major depressive disorder. However, it is important to look at the criterion used for clinical significance. NICE [The National Institute for Clinical Excellence, the independent body which assesses the efficacy of drugs] set a 3 point difference on the HAM-D [the Hamilton scale, which measures depression] or an effect size of 0.50. Leucht and colleagues examined what changes in the HAM-D correspond to global clinical ratings of improvement. They found that a 3 point difference is equivalent to a clinician rating of “no change”. To get a rating of “minimally improved” you need a change of 7 points on the HAM-D. so far, no one has been able to find a drug-placebo difference anywhere close to that in any group of patients, no matter what the severity.”
Point two, from Stavri: “Other researchers analysed the same dataset as Kirsch and drew different conclusions. Using different statistical modelling, Fountoulakis and colleagues found antidepressants were better than placebo, at all levels of depression severity. Turner and Rosenthal’s interpretation of the data is different to Kirsch’s, suggesting that certain measures can be more important than disappearance of depression, such as quality of life, which has been overlooked in Kirsch’s study, and to be “circumspect but not dismissive” in considering the benefits of antidepressants.’”
Response, from Professor Kirsch: “They made statistical errors in there calculations, which we pointed out in our rejoinder. In any case, some meta-analyses show an association of drug-placebo differences with baseline severity; others do not. Others use unconventional cut-offs for classifying severity, and some use statistical techniques (e.g., grouping Ss into severe v not severe) that all statisticians say are unreliable, akin to throwing away at least 1/3 of the data, and therefore not having enough power to reliably show real differences. More important, no one finds an overall drug-placebo difference that is clinically significant even according to the NICE criteria. So if the effect is the same across levels of severity, then no one is getting a clinically meaningful effect from the drug compared to what they would get on placebo. We used the same measure used by the FDA to make approval decisions.”
Point three, from Stavri: “Kirsch only looked at certain types of antidepressants – four types of SSRIs; your comments re relating specifically to the serotonin hypothesis and don’t relate to antidepressants in general.”
Response three, from Professor Kirsch: “There are few if any differences between the effects of one type of AD [anti-depressant] vs another. Other researchers have used different ADs in their meta-analyses. All come up with the same basic findings as did we. No one gets an effect size above 0.35 (the NICE criterion is 0.50). This includes two meta-analyses done in-house at the FDA on all the clinical trials for which they had the data. The largest found the same 1.8 point difference that we reported in our meta-analyses. Note also, that one gets the same response to Tianeptine (an SSRE) as to SSRIs.”
WHAT ABOUT THE OXFORD STUDY?
In February 2017, a study was published by Dr Andrea Cirpriani and his colleagues. I’ve discussed some of these questions with Dr Cipriani on the BBC and we agreed on most things: he said that I was right to try to get people to talk more about, and deal with, the social and psychological causes of depression. (He disagreed with me on some other points). He has now co-authored this study that has found that chemical anti-depressants have a larger effect than just a placebo.
A few people on social media seemed to think this showed some aspect of my book was wrong. I assume they believe this because (as detailed above) a Guardian blogger named Dean Burnett claimed that my book tells people to stop taking anti-depressants and this idea got quite widely spread – but, as interviewers and psychiatrists who have read the book have explained, my book doesn’t say anything remotely like that. The readers’ editor at the Guardian has now issued a clarification at the end of Burnett’s blog posts. In fact the book says, on page 37 (and this is a point reiterated throughout the text): “I certainly don’t want to take away anything that gives anyone some relief. If for you the benefits outweigh the side-effects, you should carry on.” That’s been my advice to my own relatives, several of whom continue to take these drugs at my urging.
The book explores some nuanced points about chemical anti-depressants, which are not contradicted by the Oxford study. Depression is often measured by something called the Hamilton Scale. As I explain above – and I’ll reiterate here, for anyone who’s skipped down to here – it runs from 1 (where you’d be joyful) to 51 (where you’d be suicidal). To give you a sense of what movement on the Hamilton Scale looks like, if you improve your sleep patterns, you gain 6 points on the Hamilton Scale, and if your sleep patterns deteriorate, you lose 6 points on the Hamilton Scale. According to the leading expert at Harvard Medical School, Professor Irving Kirsch, chemical anti-depressants give you on average a boost of 1.8 points. It’s important to stress: that’s an average.
As I explain in the book, I initially got more than that, and over time got less than that. (Some other experts say Professor Kirsch is under-estimating the benefit on the Hamilton Scale – but not by a huge amount).
It’s clear that 1.8 points is not nothing, and it’s more than placebo. For people in terrible pain (as I was), it can offer real relief, and therefore has real value. But for huge numbers of people – more than 50 percent, according to this major study, cited by the very person who wrote the Guardian blog post attacking my position – it is isn’t enough to provide lasting relief for depression. You can read that study here.
I think this is a pretty common-sense position. 1.8 points is not nothing; these drugs give some real relief to some people and therefore have some value; but they don’t solve the problem for most of us. This is why 90 percent of my book is about how we need to expand the menu of options for depressed people, to include solutions that deal with the underlying problems. Nobody wants to take anything off the menu.
Professor Kirsch explains about the Oxford study, via email:
There is not much new in this study, despite the media hype, and it does not contradict what I have written in the past.
One. They find a statistically significant difference between drug and placebo. So have my colleagues and I in the various meta-analyses we have published [as Lost Connections reports]. The question is whether this difference has any clinical relevance [i.e. whether it gives the user a significant movement on the Hamilton Scale]. They do not address this issue. All of the meta-analyses addressing this issue, including those by proponents of antidepressive medication, have failed to find clinically meaningful differences, using the cutoffs proposed by the National Institute for Health and Clinical Institute for Health and Care Excellence (NICE). Furthermore, Joanna Moncrief and I have demonstrated that the NICE criteria are overly liberal, as they correspond to clinician ratings of no difference at all in depression.
Two. They have chosen to dichotomize scores into responders vs. nonresponders. This has been condemned by statisticians as producing biased results and tantamount to discarding 1/3 or more of the data. It also produces what Joanna Moncrieff and I have termed the “response rate illusion.” That is because the difference between a “responder” and a “nonresponder” can be as little as 1 point on whatever scale is used to measure depression. For example, a person who improves by 50% is called a responder, whereas one who improves by 49% is called a nonresponder. We have shown that a small difference in mean improvement scores corresponds to the kind of difference shown in the new Cipriani et al. study. This difference was 1.8 points on the Hamilton scale in both our meta-analysis and a more recent unpublished analysis of all the antidepressant data ever submitted to the FDA, the latter comprising patient-level data from 23,295 patients in 92 clinical trials. To put this into perspective, note that “minimal improvement” corresponds to a 7 point change on the Hamilton scale.
Three. They report an effect size (SMD) of 0.30 for drug v placebo. We found an SMD of 0.32. The NICE cutoff for clinical significance is 0.50. Using the criteria of “minimal improvement” you would need an effect size of 0.875.
This strongly suggests the more over-inflated claims made about the Oxford study are going too far. It confirms there is real value in these drugs, but if we get stuck at the debate ‘are chemical anti-depressants good or bad?’ we’re missing the point. They provide relief for some, and therefore have some value, but don’t solve the underlying problems for most and need to be part of a much bigger strategy. The conclusion I reached in the book – that we urgently need to deal with the deeper causes of depression, rather than just pathologizing our pain by saying chemical solutions should be the immediate response for most people – is the position of the leading medical body in the world, the World Health Organisation, and the United Nations. Take a look at what the UN’s leading doctor says on this here.
For something as devastating as depression – the worst thing I have ever been through – we need every strategy and tool on the table, as I make clear in my book. Everyone in this debate agrees, including Professor Kirsch and Dr Cipriani, that there are big social and psychological causes of depression – I write about seven in Lost Connections – and many of them are rising. We need to deal with these deeper causes urgently. We are in the middle of a depression and anxiety emergency. The Oxford study confirms that some depressed and anxious people will benefit from chemical relief (as I did for a time, as I explain in the book). That relief – based on the best evidence – will be mild for the average user. It’s not nothing – but it’s not a full solution.
All depressed people, by contrast, will benefit from us dealing with the deeper causes of depression. That’s our most urgent public health task now – and that is the subject of my book.
SHOULD PEOPLE STOP ANTI-DEPRESSANTS COLD TURKEY?
I’ve been told that one person read my book, stopped their chemical anti-depressants cold turkey, and experienced some nasty physical withdrawal symptoms. As somebody who went through really deep and painful depression for thirteen years, I send her my love and support.
To take this step – quitting the drugs overnight – is to deeply misunderstand the message of the book in two very clear ways.
I warn in the book that 20 percent of people taking chemical anti-depressants will experience very severe withdrawal symptoms when they stop, which is why I stopped taking these drugs very slowly over the course of six months. I was on 60mg of Seroxat – so for a month I alternated 60mg one day and 30 mg the next; then for two months I took 30mg every day; then I alternated 30mg one day and 15mg the next; and so on, until I stopped entirely. My strong advice to anyone who wants to stop taking these drugs (and not everyone should, for reasons I’ll come to) is to cut back as I did, with a lot of consultation and monitoring with their doctor, for two reasons. One is the risk of physical withdrawal. The other is because – as I also explain in the book – the drugs give a mostly small but real amount of relief from depression to some people.
The fact that this reader experienced such severe physical symptoms shows how serious these drugs are: nobody should start or stop taking them lightly. For me, they caused a huge amount of weight gain and affected my sexual functioning while I was taking them, while giving me only an initial burst of relief from the depression itself that sadly wore off over time. Others experience low symptoms and bigger benefits (as one of my closest relatives has): I point out in the book that people who feel for them the benefits outweigh the side-effects should carry on taking these drugs.
Nobody should ever stop cold turkey, in any circumstances – that’s dangerous and unequivocally contrary to my advice.
I think there’s a deeper misunderstanding in responding to my book this way. ‘Lost Connections’ is emphatically not an argument for quitting drugs and just trying to cope with the agony. It is an argument that as a society we need to have a much broader menu of deep responses to the pain this reader, and so many other people like her, are going through. It argues – in line with the advice of the leading medical body on earth, the World Health Organisation – that we need to deal with the deep underlying reasons why people are depressed, and give them far more support and love, and far more options for changing their lives. That – along with the option of continuing chemical anti-depressants for as long as she feels she needs them – is what this reader deserves.
This reader, alas, didn’t try any of the alternative solutions I suggest, and didn’t receive any of the extensive social and psychological solutions I say are necessary to deal with depression and anxiety. Instead, she stopped overnight, and faced the extreme unpleasantness of physical withdrawal alone. None of this is what the book recommends, and my heart goes out to her for what must have been a truly horrible experience.
I believe both these points – physical withdrawal is a big risk; we need much more extensive care and support for people with depression – are clear in the book. I’m going to add an extra paragraph to future editions, stressing even more emphatically that stopping cold turkey is an absolutely terrible idea and I implore people not to do it.
If you spot anything in ‘Lost Corrections’ that you think is not correct, the best way to contact me is to drop me a line at chasingthescream@gmail.com – on the 12th of each month I’ll post an update on what I’ve received and respond to queries.