Scientists question widespread use of antidepressants after survey on serotonin
Millions of people take them, but there is ‘no clear evidence’ that chemical imbalance causes depression
Scientists have called into question the widespread use of antidepressants after a major review found “no clear evidence” that low serotonin levels are responsible for depression.
Prescriptions for antidepressants have risen dramatically since the 1990s, with one in six adults and 2% of teenagers in England now being prescribed them. Millions more people around the world regularly use antidepressants.
“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence,” said the study’s lead author, Joanna Moncrieff, a professor of psychiatry at University College London and consultant psychiatrist at North East London NHS foundation trust.
“It is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.
“Thousands of people suffer from side-effects of antidepressants, including the severe withdrawal effects that can occur when people try to stop them, yet prescription rates continue to rise. We believe this situation has been driven partly by the false belief that depression is due to a chemical imbalance. It is high time to inform the public that this belief is not grounded in science.”
The serotonin theory of depression: a systematic umbrella review of the evidence
• Joanna Moncrieff,
• Ruth E. Cooper,
• Tom Stockmann,
• Simone Amendola,
• Michael P. Hengartner &
• Mark A. Horowitz
Molecular Psychiatry (2022)
Abstract
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n= 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n= 1869). Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n= 561), and three meta-analyses of overlapping studies examining SERT binding (largest n= 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n= 566), but weak evidence of an effect in those with a family history of depression (n= 75). Another systematic review (n= 342) and a sample of ten subsequent studies (n= 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n= 115,257) and one collaborative meta-analysis (n= 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Thank you so much Rod. Looking forward to hearing the response you get. I have always been very suspicious of antidepressants… doctors are so keen to dish out like sweeties to a sugar addict!
PS: May I ask you, are you either in holiday or retired? You have been so prolific in writing posts for a while… so just wondering. 😃
Fluoxetine (Prozac) was launched in 1987 - the first SSRI.
Thirty-five years later, we read this paper...
It is sometimes said it takes seventeen years for research to reach the GP and everyday medicine. It's taken twice that for this to appear - to be prescribed in astronomic quantities and now (perhaps) to be seen as the emperor's new clothes.
"Drugs containing the active ingredient, sertraline hydrochloride, increased in cost from £1.56 per item in 2019 to £8.89 per item in 2020/2021; an increase of 470%. As a result, the total cost to the NHS was almost £168m in 2020/2021, compared with just over £26m in 2019, an increase of 538%"
TBH I wondered if they cost pennies, and if it might be profitable for the NHS. It's profitable for someone though isn't it. Get 'em all hooked.......and then hike the price.
I think money is always at the root of any suggested major change in theory and treatment (or refusal to change) for any condition. If something starts costing more than it used to then the researchers will come out of the woodwork saying "Hallelujah, I have the answer!".
But the problem is that in the UK the answer to saving money is usually CBT delivered by IAPT (Improving Access to Psychological Therapies). Doctors and politicians think (wrongly) that it is cheaper than doctors, consultants, hospitals and drugs.
Title : The UK’s IAPT Service Is An Abject Failure
Millions of people take them, but there is ‘no clear evidence’ that chemical imbalance causes depression
Scientists have called into question the widespread use of antidepressants after a major review found “no clear evidence” that low serotonin levels are responsible for depression.
I wasn't aware that there ever was any evidence for the "chemical imbalance" theory. I always wondered which chemicals were supposed to be "unbalanced". Was there a way to measure serotonin in the brain at the time the theory was first mooted? Is there a way for a GP to get it measured now? I've never had it measured, to the best of my knowledge, despite being prescribed four or five different SSRIs over about 20 years which did nothing at all.
A chemical imbalance suggests that A and B are on a seesaw, and when A is too high, B is too low and vice versa. But nobody is ever told they have low serotonin after a test for it. So it is just like telling patients a fairy story - you can make up your own details.
I have now fixed my own depression. It didn't take a pharmaceutical company product to do it either. I needed vitamins, minerals, and thyroid hormones.
SSRIs usually need to be taken for 6 weeks minimum for any effect (or so I'm told - they never worked for me, ever). If there is no effect after that time patients are told that perhaps they should give it 3 months or 6 months or whatever. If it still doesn't work then try this one or this one or that one. If they still don't work, the doctor probably just writes in the patient's notes - non-compliant - with each failure.
At least paracetamol does something useful for headaches, usually within 30 minutes of taking an appropriate dose.
The only "useful" thing SSRIs do for most people is increase the profits of pharma companies, and in the UK they give GPs QOF points. And points mean prizes (cash).
The first time I took them I could not believe they could be legally prescribed. I liken the experience of the first tablet as “we have lift off!” I was as high as a kite . It got rid of the depression all right but I was completely off my trolley on them. They wore off after about 6 months. No idea what they did to me but it was certainly enervating initially!
I've never heard of that reaction before. All I remember from SSRIs is headaches (from Prozac), having no emotions and being a bit robotic, and certainly no joy, and losing my sense of humour. Oh, and libido? What's that?
Yes the libido has never really recovered ….which might be a good thing! I had the opposite re. sense of humour I started to see all sorts of amusing connections, one or two people seemed to be on this hyper humour wave length but it went over most people’s heads! The ones that got it were intellectual types - what convoluted minds they must have! I have virtually no sense of humour now & the penny drops long after the joke was told - that stuff seemed to make abnormal brain connections and destroyed what used to be there…for good with a little help from the thyroid disease - the icing on the humourless cake you might say!
There is an uncommon reaction to SSRI's called serotonin syndrome. It can be very serious and that euphoria, almost manic energy is a symptom. I couldn't sleep and felt hyper on them, but not in a positive way.
HiI've got Fibro and also had pretty severe post natal depression. SSRI's and SNRI'S are widely prescribed for both. I must have tried at least 6 or 7 over the years, never got on with them.
They either did zilch or the side effects were so unpleasant that I couldn't continue. I took amytriptyline for a few years for nerve pain and sleep issues but after a while I had to keep increasing the dose to get any effect and then the yucky side effects increased. And coming off of them was horrendous.
They have a place for those who need or want them, but I certainly feel they are prescribed too freely.
I took amytriptyline for a few years for nerve pain and sleep issues but after a while I had to keep increasing the dose to get any effect and then the yucky side effects increased.
I've just come off after a few months - low dose (10 to 35 milligrams). While they helped quite a bit to begin with, the side effects got worse (dry mouth, tiredness) so I dropped dose and stopped. About a week to really start feeling better.
If this is not all proof of the pudding re: general doctoring, I don’t know what is! I was having a chat yesterday on the forum about ME and fibromyalgia. It’s all in the same vein. I have had no conception about the ignorance(?) of doctors really, although I have so often been on the receiving end of this misery. Far too much trust. I woke this morning to a memory of an endoscopy which made me look like I had been hung (I am pretty sure my thyroid at that time was probably enlarged but this was years before diagnosis) after choking and attempting to ‘survive’ the procedure. I was thumping the table as my lights went out - no reaction, the nurse practitioner just kept going. Funnily enough I was escorted off the premises and I asked if there was something funny about my face, as it was burning and tingling all over. “No.” As soon as I got rid of my escort I nipped into the loo. OMG what a mess which got much worse over the ensuing days. A friend suggested I photograph it and I visited my GP who thought my husband had tried to kill me. The consultant was most apologetic “This has never happened before.” I was dumb enough to take their word. Oh I have quite the fight on my hands with this. My own character is letting me down in the face of all the proof of their shoddy work.
The thing that really gets me is that they (doctors) prescribe anti depressants instead of the ‘proper’ meds that you really need and they tell people they are depressed without any hard evidence.The fact they do that is depressing - that’s not always the same as their patient being clinically depressed.
Once they've declared someone to be depressed they can refuse to refer them to anyone else, except possibly CBT. Because why would someone who is depressed need to see a hospital doctor for anything. The GP has it covered! Oh, and they are never wrong!
[Imagine this being read in a sarcastic tone of voice.]
I was prescribed fluoxetine (Prozac) about 3 months ago. I didn’t want to take it but after finding myself standing in the middle of fields and woods crying I realised I really wasn’t at my best. I have to say that this, along with HRT (specifically oral oestrogen) has given me back my belly laughs, my positivity and gratitude which I’d lost since diagnosis of hypo. I think that we need to be careful not to write off antidepressants as ‘sweeties’ for people as this can put people off considering them when they might be what some need?. I can honestly say this has worked for me. I don’t feel high or manic. I’m just able to see the lighter side of life again 🤷🏻♀️ and I sleep like a bear (according to my Fitbit) wake refreshed and can get through most plans for most days. I work like a Trojan and have energy to spare for family and friends 😊 I’d buy a drink for whoever invented Prozac!
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