The extraordinary media hype over the latest meta-analysis of antidepressants puts the discussion of these drugs back years. Despite the fact that 9% of the UK population are taking antidepressants (1), and rates of prescribing have doubled over the last decade (2), the authors of the analysis are calling for yet more prescribing. John Geddes suggested in The Sun newspaper that only 1 in 6 people are receiving adequate treatment for depression in high income countries. In The Guardian he estimates that 1 million more people require treatment with antidepressants in the UK, but by my maths, if 9% are already taking them and they only represent 1 in 6 of those who need them, then 54% of the population should be taking them. I make that another 27 million people!
The coverage was almost universally uncritical, and said little about the terrible adverse effects that some people can suffer while taking antidepressants, or while trying to get off them. Even The Guardian claimed that the new ‘groundbreaking’ study will ‘put to rest doubts’ about antidepressants.
But there is nothing groundbreaking about this latest meta-analysis. It simply repeats the errors of previous analyses. Although I have written about these many times before, I will quickly summarise relevant points.
The analysis consists of comparing ‘response’ rates between people on antidepressants and those on placebo. But ‘response’ is an artificial category that has been arbitrarily constructed out of the data actually collected, which consists of scores on depression rating scales, like the commonly used Hamilton rating Scale for Depression (HRSD). Analysing categories inflates differences (3). When the actual scores are compared, differences are trivial, amounting to around 2 points on the HRSD which has a maximum score of 54. These differences are unlikely to be clinically relevant, as I have explained before. Research comparing HRSD scores with scores on a global rating of improvement suggest that such a difference would not even be noticed, and you would need a difference of at least 8 points to register ‘mild improvement’.
Moreover, even these small differences are easily accounted for by the fact that antidepressants produce more or less subtle mental and physical alterations (e.g. nausea, dry mouth, drowsiness and emotional blunting) irrespective of whether or not they treat depression. These alterations enable participants to guess whether they have been allocated to antidepressant or placebo better than would be expected by chance (4). Participants receiving the active drugs may therefore experience amplified placebo effects by virtue of knowing they are taking an active drug rather than an inactive placebo. This may explain why antidepressants that cause the most noticeable alterations, such as amitriptyline, appeared to be the most effective in the recent analysis.
Antidepressant trials often include people who are already on antidepressants. Such people may experience withdrawal symptoms if they are randomised to placebo, which, given that almost no antidepressant trial pays the slightest attention to the problems of dependence on antidepressants, are highly likely to be classified as relapse.
The analysis only looks at data for eight weeks of treatment, whereas in real life people often take antidepressants for months or even years. Few randomised, placebo-controlled trials have investigated long-term effects, but ‘real world’ studies of people treated with antidepressants show that the proportion of people who stick to recommended treatment, recover and don’t relapse within a year is staggeringly low (108 out of the 3110 people who enrolled in the STAR-D study and satisfied the inclusion criteria) (5). Moreover, several studies have found that the outcomes of people treated with antidepressants are worse than the outcomes of people with depression who are not treated with antidepressants (6;7), even in one case after controlling for the severity of the depression (as far as possible) (8). The huge increase in prescribing of antidepressants over the last three decades has been accompanied by a substantial rise in the numbers of people who are in receipt of long-term disability benefits due to depression and related disorders in the UK, and this is at a time when benefits for other disorders, like back pain, have been reducing (9).
Calling for antidepressants to be more widely prescribed will do nothing to address the problem of depression and will only increase the harms these drugs produce. Adverse effects of the most commonly used SSRI antidepressants include sexual dysfunction, which in rare cases seems to persist after discontinuation of the drug (10), agitation, suicidal and aggressive behaviour among younger users (11), prolonged and severe withdrawal effects (12) and foetal abnormalities (13) with some drugs. Thankfully the more severe effects are probably rare, but they will become a more significant problem if prescribing rates increase further. The harm caused by encouraging people to consider themselves as having a disease requiring long-term medical treatment is difficult to quantify.
As the debate around the coverage highlighted, many people feel they have been helped by antidepressants, and some are happy to consider themselves as having some sort of brain disease that antidepressants put right. These ideas can be reassuring. If people have had access to balanced information and decided this view suits them, then that is fine. But in order for people to make up their own minds about the value or otherwise of antidepressants and the understanding of depression that comes in their wake, they need to be aware that the story the doctor might have told them about the chemical imbalance in their brain and the pills that put it right, is not backed up by science, and that the evidence these pills are more effective than dummy tablets is pretty slim.
Many people will be wondering why on earth we are reacting to the increasing burden of human misery in this way. Why are we not asking why it is that so many people in the modern world feel miserable and stressed? What are the pressures that people are under that make coping with life difficult? I could name many – insecure or inadequate employment, finances and housing, loneliness, increasing pressure to perform and reach ever higher targets at work and school, loss of meaning in life and the disappearing nature of community in many areas. These are the things we need to focus on to stem the ‘epidemic of depression’ – not doling out ever more placebos with side effects!
Reference List
(1) Lewer D, O’Reilly C, Mojtabai R, Evans-Lacko S. Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors. Br J Psychiatry 2015 Sep;207(3):221-6.
(2) NHS Digital. Antidepressants were the area with largest increase in prescription items in 2016. Cited 2018 Feb 23;Available from: URL: http://content.digital.nhs.uk/article/7756/Antidepressants-were-the-area-with-largest-increase-in-prescription-items-in-2016
(3) Kirsch I, Moncrieff J. Clinical trials and the response rate illusion. Contemp Clin Trials 2007;28:348-51.
(4) Fisher S, Greenberg RP. How sound is the double-blind design for evaluating psychotropic drugs? J Nerv Ment Dis 1993 Jun;181(6):345-50.
(5) Pigott HE, Leventhal AM, Alter GS, Boren JJ. Efficacy and effectiveness of antidepressants: current status of research. Psychother Psychosom 2010;79(5):267-79.
(6) Ronalds C, Creed F, Stone K, Webb S, Tomenson B. Outcome of anxiety and depressive disorders in primary care. Br J Psychiatry 1997 Nov;171:427-33.
(7) Dewa CS, Hoch JS, Lin E, Paterson M, Goering P. Pattern of antidepressant use and duration of depression-related absence from work. Br J Psychiatry 2003 Dec;183:507-13.
(8) Brugha TS, Bebbington PE, MacCarthy B, Sturt E, Wykes T. Antidepressants may not assist recovery in practice: a naturalistic prospective survey. Acta Psychiatr Scand 1992 Jul;86(1):5-11.
(9) Viola S, Moncrieff J. Claims for sickness and disability benefits owing to mental disorders in the UK: trends from 1995 to 2014. BJPsych Open 2016;2:18-24.
(10) Farnsworth KD, Dinsmore WW. Persistent sexual dysfunction in genitourinary medicine clinic attendees induced by selective serotonin reuptake inhibitors. Int J STD AIDS 2009 Jan;20(1):68-9.
(11) Sharma T, Guski LS, Freund N, Gotzsche PC. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016 Jan 27;352:i65.
(12) Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review. Psychother Psychosom 2015 Feb 21;84(2):72-81.
(13) Reefhuis J, Devine O, Friedman JM, Louik C, Honein MA. Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ 2015;351:h3190.
Joanna Moncrieff 
please add this to a newspapers opinion piece. It may help may people realize why they are feeling the way they are.
I was glad to read in the article that Fluoxetine aka Prozac was rated so poorly. My worst episode of depression occured whilst taking it. My efforts to withdraw from this drug are ongoing 3 years later..currently taking 2.5 ml in liquid form after a previous attempt to go cold turkey from 20mg left me feeling worse than ever. Until talking therapies are as readily available as these drugs are, prescription rates will only increase.I wonder who was really behind this article? It reeks of big pharma.
Thinking aloud..I/we might be seen to occupying a position of”Prohibition”. Of been a Nanny State entity, denying people who want to try anti depressants. Preferrably there must be an open conversation on brain chemistry between user and health services (psychiatry..mental health services) It is about choice. Then the Hippocratic oath must be primary context. You shouldn’t be able to choose harm.
On Sat, Feb 24, 2018 at 9:34 AM, Joanna Moncrieff wrote:
> joannamoncrieff posted: “The extraordinary media hype over the latest > meta-analysis of antidepressants puts the discussion of these drugs back > years. Despite the fact that 9% of the UK population are taking > antidepressants (1), and rates of prescribing have doubled over the last ” >
I wouldn’t want to be advocating Prohibition either. I’m more of a Szaszian-libertarian on drugs (all drugs, not just psychiatric ones). I just think people should know what’s what. This latest meta-analysis certainly doesn’t help with that.
Nice piece, I’d also be interested to see what Peter Gotzsche makes of the whole affair, I suspect mostly an echo of what you’ve said. However I think you, as a jobbing psychiatric epidemiologist, do your readers a great disservice by not referencing the ACE study (www.youtube.com/watch?v=Me07G3Erbw8) when rhetorizing on the cause(s) of the depression epidemic. Of course many of the factors you name are tightly correlated with ACEs, but to my mind one necessarily causes the other
I agree that traumatic childood experiences make people more vulnerable to depression and other mental health problems and that providing safer and happier childhoods should be a social priority
Whenever I hear people talking about how they have been helped by SSRIs, or doctors talking about their clinical experience and the transformation they have seen in a patient after prescribing them; I can’t help but think they are experiencing some form of Stockholm Syndrome. They believe very strongly that the drug which has harmed them is actually very beneficial.
I imagine if you gave an SSRI to a bunch of healthy people without any “mental illness” and then stopped the treatment after several months, many of them would experience an increase in symptoms that could easily be mistaken to be depression, anxiety etc. Then when the patients reinstate the drug they feel a huge benefit as many of the withdrawal effects improve. I think it’s easy to see how both patients experiencing this and doctors observing it would find it very compelling evidence that the drugs work. Unfortunately what they are experiencing is the harm caused by being dependent upon the drug. Ironically they do now have a chemical imbalance that the drug is treating, but it was caused by the drug in the first place. They are completely correct when they say the drug helps them to function and feel much better but only because of this dependence, which could have been avoided by using other treatments to help with the original problem.
Something I am concerned about is that as more and more criticisms of these drugs accumulate at some point it will become undeniable that they cause more harm than good. Despite this latest study, I do feel optimistic as I have seen significant push back in the media. At that point many people may wish to stop them but I think it’s possible that for some people stopping the medication could be much more harmful than staying on it. It will be challenging to figure out how best to handle this situation without causing significant harm.
More research into how many people experience difficulties getting off antidepressants and how to help them is crucial. The REDUCE study is planning to look at how to help more people get off sucessfully https://www.southampton.ac.uk/medicine/academic_units/projects/reduce.page
You are absolutely clueless. I wouldn’t be alive without SSRI.
I was surprised to see that this paper simply confirmed what other meta-analyses have shown, namely a Hamilton SMD of 0.3, which is subclinical.
But then they report as a primary outcome a measure that few of us really understand, the response rate, and are able to show results that do initially look impressive. It’s the change in measure which is interesting. Why did other researchers, particularly when funded by drug companies, not use this measure? Am I right that the FDA does not recognise response rate? I must admit I am confused – do we even know what to measure any more?
Where we all need help is in understanding how an effect size so small translates into a response rate that claims to provide “the final answer”.
The most important effect of taking «Antidepressants» is that they flatten feelings. Taking these nurotoxins, as Breggin will call them, also the sad feelings will diminish (amongst other things). But – they flattens feelings also GENERALLY. That means, also the sad ones. Taking these chemical substanses might give you a breake in your sufferings giving the self healing process time to work. This, I think, might be important in the sad history of taking drugs, and mey be the main cause of the positive results of the meta-analysis mentioned. Dag Coucheron Norwegian Psychiatrist and psychoanalyst. Sendt fra E-post for Windows 10
Fra: Joanna Moncrieff Sendt: Saturday, February 24, 2018 kl. 4:35 AM Til: dag.coucheron@gmail.com Emne: [New post] Challenging the new hype about antidepressants
joannamoncrieff posted: “The extraordinary media hype over the latest meta-analysis of antidepressants puts the discussion of these drugs back years. Despite the fact that 9% of the UK population are taking antidepressants (1), and rates of prescribing have doubled over the last “
I agree with your scepticism about mechanism, and I believe that these days a pharma company would have a hard time marketing a drug without some “mode of action” worked out, true or false. The days of phenothiazines and butyrophenones that “just worked” are over. I do not believe SSRIs work by inhibiting reuptake, but it seems they do work for some people and not others. I have seen this most impressively in my mother, who suffers from vascular dementia and was crying all day. A single dose of citalopram (which proved to be too large, propelled her to a state of angry paranoia in 12 hours and then over the next 36 hours she descended via euphoria to a fairly normal state and back into melancholia. We’re still tuning it, but there’s no doubt in my mind the stuff does _something_. What exactly it does is unclear, but it does it for sure.
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Very interesting read – thank you.
Mental illness is the religion of our time. More people believe in mental illness than the divinity of Christ. Confronting the belief in psychiatric drugs ability to heal mental illness is like taking away the Christian’s Eucharist. Why can’t we prescribe less harmful drugs like cocaine, alcohol, opium and marijuana? I prescribe eating out with friends and family 1-2x per week, living below your means, and saving for early retirement so you don’t have to work at your boring job all your life.
Yes, a person who suffers from MD (genetically inherited, as even my grandmother was hospitalised in psychiatric facility), would benefit from having dinners with friends. You have no idea what you’re talking about. I would not be alive without this medication. Aim this comment at people who pretend to be depressed to get attention, not to us who actually have genetically inherited mental issues.
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Hey, thanks for this wonderful article. By the way I think that it’s actually “they’re” instead of “their” just so you know.
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Just like most antidepressants and axiolytics on the market, psilocybin targets serotonin in the brain. But since psilocybin is a naturally occurring molecule I wonder if the pharmaceutical companies will keep it out of the hands of the consumer? https://psilocybintechnology.com/nbc-news-better-antidepressants-anti-anxiety-drugs/
Fantastic article and i couldnt agree more! I cannot fathom why this has been allowed to happen for so long. Antidepressants are handed out like toffees as the first option every time but but never ask the patient what hey would prefer – many would prefer to talk.
Thanks Kathy.
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Ultimately, there are no “mental” diseases. Every mental issue (the kind of issue that would typically be treated with either psychotherapy and / or pharmacotherapy) is a physical-biological condition of the brain’s functioning. The “mental” part is just a manifestation of the underlying physical-biological issue on the perceivable and conscious level.
With that being said: I have no reason to believe that current pharmacological interventions (eg antidepressants) have any positive effect on these underlying physical-biological conditions, since they lack the sophistication to target the specific biological mechanisms.
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