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Thread: Worried about being on SSRI's for so long and possible dangers of long term use.

  1. #1
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    Worried about being on SSRI's for so long and possible dangers of long term use.

    Hi all I have not posted on here for 5 years as I have been pretty stable for this period but boy has it hit me hard again in the last couple of months. My chronic health anxiety has reared its ugly head again and I'm hoping folk on here can help me. Like a whole lot of us I have a chronic fear of taking meds I am absolutely terrified of potential side effects or other health issues being caused as a result of taking them. This current episode of mine was kicked off when I was due my covid vaccine I googled vaccine side effects and that was it I was off my head flipped. This has lead me down the fateful path of googling everything under the sun to do with meds that I am currently on. I had been on paroxetine for 16 years and 5 years ago I went cold turkey off it in 10 days (under my psychiatrists advice). I then started prozac 40mg and had been on that for 3 years until I tapered to almost zero this year. Now I am taking approx 15mg per day again due to the current situation along with propranolol and Valium again after being off both for years.

    My current fears are about the length of time I have been on an ssri now 21 years in total and if this is safe. I have seen lots of articles online about bleeding risks associated with ssris and the potential for brain bleeds this has got me obsessing about having a stroke due to the meds I am literally terrified I can't shift the fear. A lot of the literature points to the danger being greatest in the first 30 days of use along with concomitant use with NSAID's but I am concerned that the danger of bleeds may also increase or remain with duration of use of an ssri. My next equally distressing fear is the suggestion that long term use of an ssri may lead to the development of seizures again I have seen several articles suggesting this online. Basically my brain is a shit storm at the moment I feel completely trapped in my own obsessive thoughts. I am really really struggling with this.

    Thanks for taking the time to read my post Owain

  2. #2
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    Re: Worried about being on SSRI's for so long and possible dangers of long term use.

    Quote Originally Posted by owainm View Post
    I had been on paroxetine for 16 years and 5 years ago I went cold turkey off it in 10 days (under my psychiatrists advice).
    I hope he/she is no longer your psychiatrist.

    I then started prozac 40mg and had been on that for 3 years until I tapered to almost zero this year. Now I am taking approx 15mg per day again due to the current situation along with propranolol and Valium again after being off both for years.
    Taking sub therapeutic doses of antidepressants (ADs) for long periods may cause them to permanently poop-out. Also, why take a dose so low that it is ineffective and you need to take 2 other medications?

    The other problem with your med regime is benzodiazepines (BZDs) inhibit the neurogenesis mechanism by which ADs (also therapy) create the therapeutic response [1]. In light of this, BZDs use should probably be limited to a couple of weeks when first taking antidepressants just to ease the initial increase in anxiety levels, for a while after AD dose increases for the same reason and thereafter for occasional breakthrough anxiety.

    My current fears are about the length of time I have been on an ssri now 21 years in total and if this is safe.
    There would be tens if not hundreds of thousands of patients who have taken SSRIs more or less continually since they became available in the late 1980s and many of them will have been on MAOIs and TCAs before that. I am unaware of any evidence of harm from long term use. Indeed, there is evidence they reduce the risk of dementia, cardiovascular disease and some cancers.

    I have seen lots of articles online about bleeding risks associated with ssris and the potential for brain bleeds this has got me obsessing about having a stroke due to the meds I am literally terrified I can't shift the fear. A lot of the literature points to the danger being greatest in the first 30 days of use along with concomitant use with NSAID's but I am concerned that the danger of bleeds may also increase or remain with duration of use of an ssri.
    SSRIs, SNRIs and some TCAs are mild anticoagulants. The bleeding risk is low unless also taking other blood 'thinners' such as NSAIDs, or other anticoagulant medications for more than a couple of days. While they may slightly increase the risk of the uncommon (~10-15%) haemorrhagic stroke, serotonergic ADs may reduce that of the much more common ischaemic (blocking) stroke and heart attacks and even the haemorragic stroke risk may be lower than thought [2].

    My next equally distressing fear is the suggestion that long term use of an ssri may lead to the development of seizures again I have seen several articles suggesting this online.
    There are a lot of epileptics on SSRIs long term and the evidence indicates SSRIs reduce seizure risk [3].

    Basically my brain is a shit storm at the moment I feel completely trapped in my own obsessive thoughts. I am really really struggling with this.
    I suggest you stop googling. Search hard enough and you'll find evidence that every medication ever made is the spawn of the devil. Even the sugar pills will kill you if you take enough of them for long enough, not to mention the risk of choking on them, plus have you considered how many people fall under the proverbial bus on the way to/from pharmacies to pick up their meds!

    References:

    [1]
    Boldrini M, Butt TH, Santiago AN, et al. (2014)
    Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.
    Int J Neuropsychopharmacol. Dec;17(12):1923-33 (Abstract | Full text)

    Nochi R, Kaneko J, Okada N, et al. (2013)
    Diazepam treatment blocks the elevation of hippocampal activity and the accelerated proliferation of hippocampal neural stem cells after focal cerebral ischemia in mice.
    J Neurosci Res. Nov;91(11):1429-39 (Abstract)

    Sun Y, Evans J, Russell B, et al (2013)
    A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress.
    Neuropharmacology. Sep;72:20-8 (Abstract)

    Song J, Zhong C, Bonaguidi MA, et al (2012)
    Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
    Nature. Sep 6;489(7414):150-4 (Article | Study full text)

    Chen J, Cai F, Cao J, et al. (2009)
    Long-term antiepileptic drug administration during early life inhibits hippocampal neurogenesis in the developing brain.
    J Neurosci Res. Oct;87(13):2898-907 (Abstract)

    Wu X, Castren E. (2009)
    Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells.
    Biol Psychiatry. Jul 1;66(1):5-8 (Abstract)

    Stefovska VG, Uckermann O, Czuczwar M, et al (2008)
    Sedative and anticonvulsant drugs suppress postnatal neurogenesis
    Ann Neurol. 2008 Oct;64(4):434-45 (Abstract)

    [2]
    Siddu M, Bustillo A, Gutierrez CM, et al (2021)
    Association Between Antidepressants Use and Intracerebral Hemorrhage: Florida Stroke Registry
    Stroke Mar; 52 sup 1 [Abstract]

    Jensen MP, Ziff OJ, Banerjee G, et al (2019)
    The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis
    Eur Stroke J., Jun; 4(2): 144–152. [Abstract]

    [3]
    Górska N, Słupski J, Cubała WJ, (2018)
    Antidepressants in epilepsy
    Neurol Neurochir Pol, Nov-Dec;52(6):657-661 [Abstract]

    Kanner AM. (2016)
    Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the evidence
    Epilepsy Behav., Aug;61:282-286 [Abstract]

    Ribot R, Ouyang B, Kanner AM. (2016)
    The impact of antidepressants on seizure frequency and depressive and anxiety disorders of patients with epilepsy: Is it worth investigating?
    Epilepsy Behav May;70(Pt A):5-9 (Abstract)

    Hamid H, Kanner AM. (2013)
    Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs?
    Epilepsy Behav Mar;26(3):261-5 [Abstract]
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    The opinions expressed above are based on my observations and, where applicable, interpretation of cited data and are general in nature. Consult your physician before acting on anything stated.

  3. #3
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    Re: Worried about being on SSRI's for so long and possible dangers of long term use.

    Thanks for the reply and the info included. Do you have any further info on why the bleeding risks are highest in the the first 30 days of ssri treatment? Is there an initial effect which the body then adjusts to resulting in a reduced platelet count which the body then readjusts to. Also is there any evidence that a bleeding risk is increased with duration of ssri treatment, or does the body just keep producing platelets at the same level after the initial 30 day impact. You seem very knowledgeable on this subject thus I am asking these questions cause I cannot find any answers to this question myself.

    Thanks Owain

  4. #4
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    Re: Worried about being on SSRI's for so long and possible dangers of long term use.

    Quote Originally Posted by owainm View Post
    Do you have any further info on why the bleeding risks are highest in the the first 30 days of ssri treatment? Is there an initial effect which the body then adjusts to resulting in a reduced platelet count which the body then readjusts to.
    The risk isn't any higher, just that those susceptible are likely to experience problems within 30 days (or within 30 days of a dose increase). If you don't have an issue then you're unlikely to later.

    Also is there any evidence that a bleeding risk is increased with duration of ssri treatment,
    No. The main risk is taking other anticoagulants such as NSAIDs and warfarin, but maybe not NOAK anticoagulants such as rivaroxaban (which I'm currently on for DVT in addition to a very large dose of a moderately serotonergic TCA). There are a number of potent anticoagulant supplements such as fish oil, ginkgo biloba and ginseng which need to be treated with caution too. Google for a full list.

    Bottom line: if you were on SSRIs for over a decade without problems you are very unlikely to have any in the future, especially given fluoxetine is a less potent serotonin reuptake inhibitor than paroxetine. HA is a much greater risk to your wellbeing.

    or does the body just keep producing platelets at the same level after the initial 30 day impact.
    As per above, there is no heightened risk for the initial 30 days. Serotonergic ADs don't reduce platelet count. Serotonin has a number of roles in wound repair. Significant quantities of it are stored in platelets for release into blood vessel breeches to initiate blood coagulation, constrict the blood vessel and stimulate tissue cell growth. The platelets take up serotonin from plasma with the same serotonin transporters (SERT) as neurons use to reuptake it from synapses after cell depolarisation (firing) and SSRIs, etc, inhibit them too. These ADs also reduce the amount of serotonin circulating in the blood.
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    The opinions expressed above are based on my observations and, where applicable, interpretation of cited data and are general in nature. Consult your physician before acting on anything stated.

  5. #5
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    Re: Worried about being on SSRI's for so long and possible dangers of long term use.

    Thanks again can you explain what exactly fluoxetine is a less potent serotonin reuptake inhibitor than paroxetine means I cannot really find a easy to understand answer online

  6. #6
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    Re: Worried about being on SSRI's for so long and possible dangers of long term use.

    The binding potential of a drug to receptors, or in this case the serotonin reuptake transporter (SERT), is determined by the plasma concentration of the chemical (ligand) required to block 50% of the receptors/transporters in nM/L expressed as the inhibitory constant, aka Ki value. The lower the Ki the stronger the binding affinity

    The SERT binding potential for paroxetine is ~0.34 Ki, that of fluoxetine is ~1.0 Ki, however, unlike paroxetine, fluoxetine has an active metabolite, norfluoxetine, aka desmethylfluoxetine (it does most of the work), which has a much lower SERT affinity than the parent compound at ~19 Ki. I don't have a combined Ki value, but it will be lower than for fluoxetine alone.
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