Serotonin, Depression and SSRI Antidepressants

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Orangeblossom
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Serotonin, Depression and SSRI Antidepressants

Post by Orangeblossom »

I have been taking prozac since 1999 on and off, it has really helped me with depression and I found it helped me think more clearly and get my degree a couple of years later. Now finding I have the APOE4 gene, I tried to look into the affects of taking prozac and found it promotes neurogenesis in the hippocampus, and may be useful in AD. Here is a link I found about it in case it is of interest to others. I know that there are other ways to increase serotonin in the brain for others not wanting to take anti-ds, for example the supplement 5HTP, foods containing tryptophan or the herb St John's Wort, often used for seasonal affective disorder.

https://www.sciencenews.org/article/ant ... lzheimer’s
Last edited by Orangeblossom on Mon Mar 05, 2018 7:10 am, edited 1 time in total.
Erdene
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Re: SSRI Antidepressants

Post by Erdene »

Thank you many times over for that article! I have been on prozac since 2002 and it is very difficult to withdraw. I was able to cut down to 10 mg every day in 2005 (that took 6 months) but was in a severe car accident and had to resume the 20 mg.

I have been thinking of trying to withdraw again but will stay tuned....

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Re: SSRI Antidepressants

Post by Orangeblossom »

I too, tried to come off it recently and had side effects so have started again. It seems to help me and doesn't have many side effects for me while taking it.
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Re: SSRI Antidepressants

Post by Orangeblossom »

I also looked into cardiovascular health and prozac and found it seems to have a slightly blood thinning affect and people on it had less cardiac problems that those with depression overall.
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Julie G
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Re: SSRI Antidepressants

Post by Julie G »

FWIW, I think the jury is still out with regard to the effect of SSRIs on Alzheimer's risk. Here's an article describing a recent study suggesting they increased risk. I also recall Howard Federoff's work from several years ago demonstrating that folks who convert to AD had lower levels of serotonin in peripheral lipids... not sure how that fits. Do SSRIs increase serotonin or do they work by way of another mechanism? I suspect we have more to learn. Many members recently shared helpful strategies for depression in this thread.
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Re: SSRI Antidepressants

Post by Orangeblossom »

They increase serotonin by reducing the rate up uptake to the next neuron, so increasing levels in the brain. (to increase serotonin levels in people with depression, the idea being serotonin makes you happy, basically, and those depressed are lacking in it).
Yes there are various types of antidepressants, i mainly looked at prozac. The older tricyclics like amitryptilline (which can be used small dose for pain management as well) or to aid sleep, I know have some cardiovascular affects such as heart rhythm problems and may cause metabolic affects as well. I guess it maybe depends on the particular one. I also read that article and thought it wasn't very clear whether the meds were linked with the problem or depression itself. Thank you for sharing, as with many things it seems to be inconclusive as the affects overall.
"He wondered whether it is the depression itself, or the drugs used to treat it."
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Re: SSRI Antidepressants

Post by Orangeblossom »

This is an interesting recent UK study about serotonin and increasing it using an SSRI improving symptoms in dementia.

http://neurosciencenews.com/serotonin-d ... vity-2164/

"citalopram boosted activity in the dementia patients in their right inferior frontal gyrus, a critical region of the brain for controlling our behaviour, even though this part of the brain was shrunken by the disease."

This link is about serotonin and it's link to dementia

http://www.empowher.com/dementia/conten ... a?page=0,0
Last edited by Orangeblossom on Fri Nov 10, 2017 1:37 pm, edited 1 time in total.
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Re: SSRI Antidepressants

Post by Julie G »

Agree, that it's just correlation and pathways (if causative) are unclear. Here's the paper:

The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta‐analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347943/
Abstract
1. Objective
To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD).
2. Method
We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model.
3. Results
Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25).
4. Conclusions
Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention.
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Re: SSRI Antidepressants

Post by Orangeblossom »

It is confusing, as how can it determine between those with depression on antidepressants, and those without depression, through doing a study like that? How do they know it came from the drugs and not the underlying condition? Cognitive impairment itself is associated with depression? "This association may arise due to confounding by depression or depression severity"..

"biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible." I wonder what these are. Maybe I will check the references and see.
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Re: SSRI Antidepressants

Post by Orangeblossom »

This is interesting. In the full article it says how they did the search.

"Searches were carried out with a combination of the following key words: Antidepressant, antidepressive agent, thymoleptic, depression medication, depression therapy, depression treatment, monoamine oxidase inhibitors, SSRIs, tricyclic antidepressant, AD, dementia, demented, cognitive impairment, cognitive loss, cognitive deficit"

So they didn't just look at new, SSRI type anti-ds but the old ones like tricyclics as well. It would be better to have had a study with the different types separated perhaps. Yes, it mentions that.

Thank you a really interesting article and worth reading the full version.

"Finally, as stated above, most cases of AD/dementia are influenced by factors such as advancing age (65+ years), biological sex and whether one carries the ε4 allele of the APOE gene (the only genetic risk unquestionably associated with the late‐onset form of AD). Interestingly, the APOE ε4 status is also associated with clinical depression, but only in women (Muller‐Thomsen et al., 2002), and particularly those with a history of depression prior to developing AD (Delano‐Wood et al., 2008). The interaction of ε4 genotype and depression further increases the risk of incident dementia (Geda et al., 2006). It would be interesting to revisit some of these larger population study datasets—for example, the extensive dataset associated with the Danish study (Meng et al., 2012)—to determine whether biological sex, APOE ε4 genotype (if described in the patient files) and specific antidepressant drug usage (including for off‐label indications (Wong et al., 2016)) interact to impart greater odds of developing a dementia‐related phenotype."
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