Policy making science requires 'randomized control trials'.
mTBI is too heterogenous to conduct research by randomized control trials.
mTBI is a silent epidemic because policy makers never see any evidence.
The Glasgow Coma Scale (GCS) is a mortality prediction scale not a brain injury scale.
CT and standard MRI scans are macroscopic, ie as seen with the human eye, they cannot 'see' microscopic cellular damage.
Brain damage in mainstream health systems is assessed by the GCS and CT/MRI scans. Meaning your brain damage is not being assessed.
Neuropsychology assessments can identify potential dysfunctions through testing.
Neuropsychology assessment results + GCS and CT/MRI = psychological dysfunction not brain injury. (Same for medico-legal)
The car and sporting industry conducted injury simulations on animals from rats to great apes and scanned with Diffusion Tensor Imaging (DTI) that 'sees' microscopic damage. After mTBI they found fluid diffusing from axons.
Histopathological (sliced brain seen under a microscope) evidence of the brains found damaged and sheared axons.
Postmortem histopathological examinations of people with mTBI that had died of other causes found they had damaged and sheared axons.
fascinating. I feel like these are all good starting points for discussions I may have with ‘experts’. I’m am involved in a claim against the driver’s insurance company and am about to embark on about six months of assessments with various medico-legal experts. Posts like this can contribute towards helping me go into it with my eyes open as it were. Thanks for sharing your findings and putting the work in.
I'm 3 and a half years into a legal claim and therapy for the same thing good luck with your journey I'm not going to lie it's a tough tough process with ups and downs keep strong on bad days my friend as there will be plenty of them
thanks for your support. I notice we’re the same age. As if tbi is not a good enough reason to have a connection, I noticed your age and I thought ‘cool’. Me, you and Star Wars. The world has never been the same since!
Interesting stuff PV. What are your sources and study sizes on dementia and antidepressants - and who funded the research initially - because I did find research on SSRI and SNRI which my consultant ( tutors in London teaching hosp) also referenced and did discuss with him showing they produce a therapeutic effect on the white matter after brain injury - so the reverse of what you found?
As a population we are predisposed to depression ( both from the injury and dealing with it) and I think the potential harms and benefits of not taking antidepressants need to be carefully weighed up in each case. I was definitely suicidal and highly anxious after my TBI - duloxetine allowed me to function again - with no withdrawal issues when I came off it either.
Grotty fact on Alzheimer's Research UK site - Apparently 1 in 3 people born this year in the UK population will develop dementia in their lifetime. Against 1 in 3 odds, I suspect it is quite difficult to pull out the effects of BI and antidepressants from the overall lifetime risk? Particularly if you take into account the possibility of reduced exercise, nutrition and social interaction that can arise post BI.
Canadian study over ten years with 13,000 participants, bomb proof. Also recent meta analysis on all antidepressants for over a decade found no efficacy for treatment. I agree the choice though is for the individual, but they should have all the facts to make the decision in the first place.
Bear in mind they would be weighing up a small potentially increased risk that may not actually be causative - re the research you have given the link to here - against the immediate risk of self harm. The facts need to be given appropriate weighting. Plus many of the symptoms of depression overlap with PCS - so can leave people on an increasingly downward spiral of dysfunction without immediate help.
Wouldn't put a great deal of weight on this study personally PV - and would critique it carefully in a masters. This is the retrospective study you mentioned link.springer.com/article/1...
They looked at the records of roughly 30k older adults ( at least over 60s presumably?) on Medicare, that were admitted to hospital for TBI. They found 23k recorded adverse events - so most people admitted suffered a stroke or bleed of some kind - something like 76% - unless certain individuals had more than one adverse effect, which I suppose is likely?
They then linked the adverse effects to the class of antidepressants administered - not sure from the abstract if all the 30k were given antidepressants, but if for example, they were selecting the records of people being given antidepressants to look at particularly, I'd be interested to know how they randomised the sample - because if essentially it was a stratified sample, then I would have thought the study would carry less weight statistically. Plus it's not clear from the conclusion what other drugs or treatments were given and how they dealt with any confounding factors.
They concluded that compared to tricyclic antidepressants that SSRIs ( but not SNRIs) were associated with an increased risk of haemorrhagic stroke in this particular population, but not for any other adverse effects studied, such as ischaemic stroke or seizures for example. The wording in their conclusion is slightly odd in that they say that compared to SSRIs actually no adverse effects were associated with SNRIs or tricyclics/ TCAs.
Interestingly enough NICE here advises against tricyclics like amitriptyline for older adults because of the anticholergenic effects it has - obviously not ideal for older adults that have been hospitalised for TBIs . Plus amitriptyline itself isn't usually the drug of choice these days for depression, hence the manufacturers repositioning it towards pain relief now.
But based on the conclusions of this study, it appears that SNRIs like duloxetine are not implicated in increased risk of haemorrhagic stroke after hospitalisation or other adverse effects.
Have you looked at what company commissioned the study, and if any of the scientists involved were doing any work for the manufacturers of any SNRIs or tricyclics around that time? That's always worth looking into.
The crux of scientific research is what side of the fence you sit on, who pays for the research, is it competing pharmaceutical sources. It's the same for every 'scientific' argument in the Brain injury world, from every aspect from diagnostic to legal perspectives, to all treatments, to all after care. The conclusion is that the scientists don't have a clue themselves hence so many arguments. My argument will be there is not enough input from people with brain injuries themselves, first hand accounts, subjective experience, people with brain injuries have no say in the science from their own experience. It's a totally untapped area, Thesis discussion.
Well, what is clear is that the study you found and referenced, carried out in an elderly population admitted to hospital for TBI (so on the severe end of the scale - with a high level of adverse events such as strokes) found no harms associated with taking SNRI antidepressants - whereas your hypothesis is that the brain injured shouldn't take any antidepressants (which as you know I strongly dispute). From my point of view that's jolly interesting, because that's what my neuropsychiatrist prescribed me, rather than the SSRIs that tend to be prescribed by GPs, judging by the experiences on here.
I'm not sure you're being exactly fair to scientists PV. The truth is they have been establishing the impacts of brain injury for years, but it takes time for this recent research to trickle down into general practice. A great deal of work has been done since 2012- 2014 with FMRI scanners in research settings, which show up physical signs in TBI brains, but many of the GPs and consultants we see will have been trained before then - and while obv they have to do CPD like everyone else, their early training, which historically has been divided into two schools of thought (mental v physical) is likely to have had an effect on their practice. I find it interesting that the relatively young central London consultants I got to see - who it actually turns out were pretty enlightened in terms of their approach to rehab, based on what you're suggesting is a good practice - were also all lecturers themselves - so good practice in treating brain injury is being taught and disseminated within the medical profession right now.
From our point of view on the receiving end in the ' front line' that won't always be our experience - as we well know from the posts in this forum - some of that will be down to NICE, some will be down to political decisions, some of it will be down to the fact that we will just happen to get referred to neurologists who haven't specialised in TBI - or are just older. But that can't be blamed on the scientific community. I think the advice often given on here that neuropsychologists and neuropsychiatrists are usually clued up on BI is a good rule of thumb - as is always checking whether the neurologist you're referred to specialises in your own brain injury - are a good start for getting in front of the right people - as is your tip that we also need occupational therapy for oculomotor and vestibular exercises.
The other thing is that the onus is on the researcher to both evaluate the quality of the trials and studies done, by critically appraising the work and by proactively identifying any bias - lecturers can often help there - they are usually well aware of individuals that do work on a regular basis for any particular companies or vested interests. (Studies on Ritalin for ADHD in children are a case in point - a few years ago virtually all the research against using Ritalin was ultimately funded by a weird religious group in the States).
You may not be getting what I'm saying. All sides in these scientific arguments don't have a leg to stand on if there is no definitive proof, a physical measurable entity, a gram of mass, a speed of light, a meter of length; not a psychological theory. A researcher can make a case from any published research that has a DOI number, meaning it is peer reviewed. I discus both the pros and cons, limitations in my thesis work, all science has limitations. I'd be interested in a peer reviewed paper, if you have a reference, that says a weird religious group in the US influenced Ritalin research.
I agree the front line does not know what TBI's are so they have no idea either what effects any medications have long term ie stroke and dementia.
Check out the IMPACT and CRASH studies funded by the WHO. The drug research is interesting, people with TBI are basically guinea pigs.
Raquel C. Gardner, MDa and Kristine Yaffe, MDa,b,c
Nyam, T. T. E., Ho, C. H., Chio, C. C., Lim, S. W., Wang, J. J., Chang, C. H., ... & Wang, C. C. (2019). Traumatic brain injury increases the risk of major adverse cardiovascular and cerebrovascular events: a 13-year, population-based study. World Neurosurgery, 122, e740-e753.
Wang, Y. C., Tai, P. A., Poly, T. N., Islam, M. M., Yang, H. C., Wu, C. C., & Li, Y. C. J. (2018). Increased risk of dementia in patients with antidepressants: a meta-analysis of observational studies. Behavioural Neurology, 2018.
Interesting facts. MY research has shown that Brain Injury is a qualitative problem, not a conventional quantitative scientific problem. The classification of BI as minor, moderate or major is unhelpful. GCS is of very little use for nearly all patients. As with most diseases BI is socially constructed and therefore not static. In other words it has and will change over time... For example, a bash on the head in a rugby scrum is now consider to be a trauma. There are clearly a broad range of BI events that will be classified differently over time.
Much of the literature focuses on catastrophic brain injury. Statistically this type of BI is rare. The minor-moderate spectrum is very nuanced and very difficult for medics to classify.
The of antidepressants is rife (as many BI survivors are understandably depressed) and there is an increasing use of anti-psychotic to help damage (sedate) behaviour of concern. This is a nasty dynamic that acts like a chemical cosh (remember one flew over the cuckoo's nest.)
The elephant in the room is how do we deal with a large population of BI survivors (moderate/minor/major) who are depressed that their accident has ruined their life. How do we help people who are deeply depressed and are having suicidal thoughts? I don't think sedation is the solution ...
If people were given the truth that 'minor BI' is caused by axonal injury and the health system adopted realistic neuroplasticity therapies people may not end up depressed. From what I can tell depression comes after a brain injury from the sense of hopelessness when facing the fact that there are no treatments in the health system. Depression is a secondary problem that develops from not treating the primary cause.
I think that if anyone is deeply depressed and suicidal that antidepressants definitely have their place - bearing in mind this is regarded as an urgent medical need - and we know that the best result is to combine these with talking therapy. My neurologist sent me to his team that provided occupational exercises for vestibular and oculomotor issues, graded exercise for autonomic dysfunction and to prevent deconditioning, neck manipulation for the headaches, talking therapy that looked at how I had coped with adversity in my past and was also geared towards acceptance, coaching to handle fatigue from everyone, and yes antidepressants - which lifted the cloud of anxiety I had quite miraculously - duloxetine was the drug of choice because of the pain relief angle. The combined effect was to stop my 24/7 headaches and post traumatic migraine attacks. I came off duloxetine without withdrawal symptoms after nearly 18 months - but did notice an uptick of my background headache - though managing my fatigue is the main key for managing headaches. I think the duloxetine most likely helped me to keep my mood level and persevere with the rest of the rehab. I'm actually more annoyed that as a single older woman there wasn't some discussion about the effect of them on libido. On the other hand I did stop speculatively eyeing up the knife drawer which was obviously a rather good thing. Do I think that the relatively low cost of occupational therapy should be available to all MTBI sufferers - yes totally - it improved my overall functionality incredibly, and it is ridiculous that it is not readily available.
I think it's quite clear that TBI does give us more risk of dementia and possibly an increased risk of Parkinsons, which is not a pleasant prospect - but how much of this is down to injudicious drug use, and how much is down to all the factors we know are causal in dementia in any case - poor sleep, lack of exercise, lack of social interaction, and poor diet ( fatigue plays hell with meal planning obvs) is doubtful.
There are 4 or 5 references I sent. What I'm doing in this part of the research is finding out how PCS is diagnosed and treated. Health systems use GCS and CT scan combinations that do not show any damage. The symptoms of PCS therefore are considered psychological and the treatment antidepressants.
The automotive and sports industry don't use GCS and CT scans. They use Diffuse Tensor Imaging and bio-mechanical modelling. This shows brain damage at a cellular level, the axons connecting functional regions of the brain are sheared and damaged. The symptoms are lack of brain function connectivity or functional neural disorder (FND) and the treatments are repetitive neuroplasticity exercises.
PCS increases the risk of dementia. Antidepressants increase the risk of dementia in normal people. So if antidepressants are used for PCS the risk is accumulated. The question is whether FND is being misinterpreted as depression.
Yes, which is why I imagine my neurologist sent me to the sports physio he works with who specialises in concussion ( this chap - Theo Farley iseh.co.uk/news/latest-news... ) Certainly the neuropsychiatrist he also sent me to, said in my case they 'were throwing everything and the kitchen sink' at it because I'd got to them within the first year. While my improvement was startling under the joint regime, I'm certainly not 'fixed' completely - though in a much better place than before the rehab - which is the problem for NICE I suppose?
I'm not sure that you have clear causality for antidepressants and dementia in normal populations - the problem being that the risk of dementia is very high in the first place in the general populations - 1 in 3 of people born this year - and that as the authors of that Taiwan meta study you've found say, depression is one of the early symptoms of dementia anyway.
I think that it is also possible that people with BI will still get depression as a sequelae of the injury even if they receive confirmation from their medics that their problems have a physical cause. Because that is also depressing in itself, given the wide ranging issues our population deal with. But there are so many crossovers between the effects of MTBI and depression that I'm not sure you can identify a line between them - and certainly concomitant depression will make recovery less likely, whether caused directly by the injury or as a result of dealing with the consequences of the injury. Could I have managed to do without the duloxetine and just had the acknowledgement of the PCS, the exercise regime and the talking therapy - yes, possibly, but given the crippling anxiety that lifted with the drug use - which I wasn't aware I actually had - I am not totally sure. So withholding antidepressants on the outside chance that they affect future health is gambling the certainty of poor present day healthy functionality against possible but unproven harms in old age - and would probably not be ethical?
Also take into account there are drugs that treat health problems besides depression, that do have adverse effects on the brain which we would perhaps do well to steer clear of if possible - anticholinergics are a case in point. drugs.com/article/anticholi...
I'll be interested to see how the NICE guidelines change with the ABI Bill findings. Neurofunctional disorder caused by axonal injury is now standard in the literature following mTBI. Psychological problems develop later when trying to adjust to life, they are not caused by the physical injury to the brain.
But of course by the time we have passed the magic three month mark and start seriously engaging with the medics, depression - given jobs and loss of functionality, is likely already a factor, given it is usually the longest period of ill health any of us have suffered - I take it you're not advocating withholding antidepressants?
I would advocate for presenting all the evidence from both sides of the argument and let the patient decide. A bit like smoking really, smoking helps reduce anxiety but!!
Not sure you can put smoking and antidepressants in the same category of harm!
Many types of drugs for many health problems have an anticholinergic effect that increases the risk of dementia - including amitriptyline - the effects of these are already well evidenced and documented
If I remember correctly you had private rehabilitation not standard NHS, your sports injury therapist (just read your link) is following the 'functional brain injury paradigm' which recognises that the symptoms ARE caused by a physical brain injury. Part of the argument I'm making is that on the NHS and in the legal system the symptoms are from psychological and not brain injury causes. The NHS and legal systems are out of date and the ABI Bill should result in a paradigm shift toward the functional system and actually treat the brain injury. The knock on effect will be to reduce many of the secondary psychological symptoms.
The only people arguing against this the are sponsored by the pharma and insurance industries. The give-a-way in the literature is that patients are often described as 'claimants.'
Yes, I got lucky if you like - I had the company medical insurance to fall back on - albeit that because a neuropsychiatrist was involved they capped the annual amount they would pay out for him and the neuropsychologist, and tried several times to claim that they wouldn't pay out for headache /migraine treatment because they unilaterally classed it as a chronic condition. Ultimately I paid about half my medical bills from savings - and am definitely uninsurable now. A clear case for keeping the NHS from morphing into an insured system actually. My first neurologist was running out of ideas, but believed it was a physical not mental problem, and referred me to a neurologist friend of his in London whose team, including the neuropsychiatrist, were also adamant that the problems I had were a physical result of a brain injury. I agree that exercises and talking therapy should be available on the NHS - which would be a relativity low cost intervention. Whether compared to antidepressants, which I firmly believe that some of us do need as well, I don't know if it would meet NICE value for money criteria - given that I didn't get back to work for example.
Given that there are various drugs that can affect the brain, while I agree with you that TBI shouldn't be classed as a mental condition rather than a physical one, I think - particularly given the problems we face as group - it is wrong to single out of only one class of drug as a culprit in worsening dementia - as there is a basic resistance to taking antidepressants at the best of times - and for example, the range of anticholinergic drugs have better quality evidence regarding dementia causation.
Coming to this rather late but wanting to add my own quite limited experience with a low dose of nortriptI lyne following a fall in January. I started on the 10mg dose and the immediate effect on me was extreme tiredness, I felt drugged and not in a good way. I persisted for the three weeks to establish tolerance and then moved up to 20mg as advised. I had one day of feeling pretty good, no headache of any kind, but after that, the impact on my mood was intolerable.
I have practised yoga and meditation for many years and, throughout an often stressful working life, I was always asked how I managed to keep so calm in some quite challenging situations in multi-million dollar projects when things weren’t going quite to plan (as in, the typical experience of any large scale project).
After only three days on the 20mg dose I began to have the most horrendous mood swings and got into a very intense and unpleasant argument with someone very close to me.
It didn’t take a lengthy RCT to identify the culprit! I immediately began to taper back down to the starting dose and, on the advice of a pharmacist, spent one more week at 10mg and then stopped. I actually chopped the tabs in half so had a much gentler reduction in dose.
Behold, after the removal of the nortriptilyne, my calm rational self had returned, along with my ability to think straight albeit with some memory challenges.
Am I an outlier in this experience? Hard to tell, but I have always had a high sensitivity to prescribed drugs. After a back injury ten years ago, I removed tramadol from my pain meds as the pain was preferable to the terrible psychological impact of opiate treatment.
The broad spectrum impact of nortriptalyne was clearly something that had a huge impact on my psychological well-being in a way I really hadn’t anticipated.
We can compare research findings ad nausea but the simple fact that individual responses to a medication can vary wildly becomes a challenge in the choice of treatments.
Recent work by Imperial College has shown rather convincingly the benefit of psychedelics on depressive conditions with massively reduced harm when compared with the gold standard of escitalopram - this is thought to be due to the neuroplasticity that classic psychedelics have been observed to trigger along with measured increases in brain connectivity across disparate regions.
If we are talking about loss of function, then any treatment that hinders the brain’s natural plasticity probably isn’t an especially wise choice. However… we are a long way from gaining acceptance of this due to the points you made earlier about out of date training along with tabloid shock/horrors whenever mention is made of psychedelics or similar.
(As an aside, MDMA has recently been approved by the US FDA and in Australia as a treament for PTSD; chances of that ever happening in the UK….?)
Granted it takes a long time to shift treatment attitudes but when we are the people at the suffering end of the shitty stick I think it’s important to fuel the brain’s natural desire for plasticity rather than douse it.
That the continued prescription of drugs like nortriptilyne or similar doesn’t stand up against more recent research that demonstrates how plasticity can be nurtured via targeted administration of psychedelics.
Also, that individual responses to ‘accepted’ treatments is highly unpredictable and potentially psychologically damaging.
The research with psychedelics is for emotional and psychological issues and is being done at Imperial College in London. The MDMA research is being carried out by the US military. Both are in the very early stages. I think I read somewhere that magic mushrooms, psilocybin is being trialed in Canada in regard to mild TBI symptoms but it will be years before anything mainstream comes of that if at all.
The MDMA work has moved into clinical practice for PTSD in four countries since July 23.
Granted that the research in psychedelics has focused on psychological conditions up to now, but plasticity is plasticity and any consequent neural rewiring is likely to have impacts on other functional domains.
Clinical testing will certainly take its time but I think it's fair to offer up a hypothesis that this could be an accelerator for restoring cognitive function in key domains.
Not sure it is correct for brain injury because psychedelics mainly induce activity in the right hemisphere of the brain. The cognitive training required for conceptual processing which is linear and language based for rationalization, requires left brain activity in the alpha and theta 3-8 wave bands. This is done by targeted repetitive concentration. Psychedelics produces nonconceptual images which are functions of the right hemisphere. It may help with damage to the right hemisphere but as everyone knows the right hemisphere is the unconscious part of the actively functioning brain. The left hemisphere inhibits the right hemisphere when rational thinking is required.
Hi Stubble, yes, nortriptyline is a tricyclic like amitriptyline, so presumably also anticholinergic - so also bad news particularly for older people like me. Amitriptyline made me incredibly groggy when I took it. I tolerated it better than some other migraine meds, but that's not a exactly a recommendation. My neuropsychiatrist said that some of the original research has been repeated on it, using higher modern day standards, and it's main beneficial effect is that it makes you sleep, which can improve other aspects of TBI - but he added that there were other better drugs to help people sleep. (Same as there are better drugs to help with TBI). I suspect that now is not the med of choice for depression, that there is a general search for uses for it. I still find it worrying that tricyclics are so freely used for TBI. Ok you get a mild antidepressant and sleep effect with a familiar drug that's been arrived for years, but as it's anticholinergic that's not a good solution.
I read the post with a lot of interest as I had a concussion in January 2020 and I am not fully recovering mainly concerning emotional symptoms: I feel less involved in emotions as, for instance, music listening, than before the injury (see for instance:
psycnet.apa.org/record/2014... where the statements of the post seem to be confirmed. I am in the Italian health system: I met three neurologists who told me that I am simply depressed as my CT scan is clean and they prescribed antidepressants. I also saw a psychologist who told me that I am not depressed and she believed I have a "true" PCS .
I am not taking any drug but I would like to treat my symptoms properly: this is the dilemma now! Thank you again for the post.
Hold on PV - your study you gave the reference for below - that found that antidepressants increase risk of dementia isn't a Canadian study - it was done in Taiwan in 2018 based on five previous observational studies that they selected for their meta-analysis - that looked at SSRIs, tricyclics and MAOIs . Unless you have another reference you haven't quoted? Did you find any other studies with different findings so that you can compare and contrast them - as I suspect there has been studies done on both sides of this debate - ideally you need to review both for your masters. Indeed, the introduction to the paper you cite states that the evidence is inconclusive and there have been studies that show that antidepressants improve cognitive function in Alzheimer's patients. The paper you gave the reference for concludes that unnecessary prescription of antidepressants should not be given to patients that show signs of dementia, It also states that their study could not clarify whether the observed association between antidepressants and risk of dementia is causal - and mentions earlier that depression can actually be a symptom of the onset of dementia.
I think I'm right in saying that depression on its own is an increased risk for dementia - there's been a study published recently.
We know that amitriptyline is one of the anticholergenic drugs - so that would make sense as these are not meant to be prescribed to over 65s anyway because of this.
Wow pink that was an interesting read with coffee this morning I would love to read more about the effects of antidepressants on bi survivor's if you can give me some links to some good pages ? I stopped taking mine 2 months ago as I said they were not helping and with some making my brain worse 🙃 after reading your post it looks like I was right so thanks for posting some true facts 👍
My massive thanks to all involved in this discussion.
I have my own views but it is good to contrast and compare other detailed opinions and science, some of which seem correct, others not so. (I disagree strongly with the linked study about music in my case)
I suppose I am very lucky in that I have always been observant and analytical, plus weigh up all sides of an argument before drawing conclusions. Having spent time in academia as well as the commercial world probably assists too.
More than any clinician or study though, I am greatful that I have always kept notes and diaries of thoughts, so I have been able to refer back to these thoughts and actions made well before my TBI and that is something that no outside assessment by others have been able to fully access or understand.
Equally until anyone has sadly been through this experience few people can even comprehend what it all means or the negative effects they can cause.
Not everyone gets a second chance at life.
So some degree of self assessment and for the record, avoidance of drugs (I even refused sleeping tablets in hospital) means I do try to make the most of everything I can.
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