Serotonin, Depression and SSRI Antidepressants

[Orangeblossom]

I see. Yes some studies say less receptors with progression of AD also. Therefore less serotonin. It's all interesting.

[Fiver]

This is interesting....I'm following the discussion.

One note: wellbutrin (buproprion) was mentioned. As you probably know this is a different type of AD, not a SSRI. It increases dopamine and norepinephrine, as I recall, not serotonin. I assumed that case mentioned in the book where a person's buproprion dose was reduced was aimed at lessening any increases in heart rate, stress markers, or anxiety that might occur. Usually these aren't problems. But I could see how a doctor might suggest cutting back, if possible, just in case there was an indirect impact on AD for that patient. Just my thought. Not a medical doctor.

[Orangeblossom]

Ok, thanks for mentioning that Tom, I'm not familiar with Wellbutrin and assumed it may be an SSRI. I think SSRIs such as prozac have less of those side effects, not sure though. I know prozac has a long half life in the body compared to some, making it easier to cut down the dose...around one week I think. An interesting book on prozac is called Listening to Prozac, about how it makes some people 'better than well' and issues around it, in general.

[MarcR]

This issue is near and dear to me as my wife is 15 months into a Prozac withdrawal nightmare. I would encourage anyone thinking of beginning to use an antidepressant to visit Surviving Antidepressants, which is a forum site much like ours here with 7,000+ members. The harrowing personal experiences shared there offer a compelling rebuttal to the manufacturers' assurances that these drugs are benign and non-addictive.

[Orangeblossom]

I'm sorry to hear that Marc. I think it saved my life, to be honest. And helped me get my degree. So I am really grateful for having it. But sorry to hear they have cause such problems for people. My doctors and I have agreed I need to stay on it for life now. But finding cutting down is not too bad, as it has a half life it is usually one of the easier ones to come off or reduce. I get on with it much better than the ones with a shorter half life like sertraline for example. I hope your wife finds a way forward with it and feels better soon.

Oh, PS if your wife might benefit, there is a good supportive site called Elefriends run by Mind it is here. www.elefriends.org.uk

[Julie G]

Brand new paper:

Impact of SSRI Therapy on Risk of Conversion From Mild Cognitive Impairment to Alzheimer's Dementia in Individuals With Previous Depression
https://www.ncbi.nlm.nih.gov/pubmed/29179578

Abstract
OBJECTIVE:
Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia.
METHOD:
Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates.
RESULTS:
In MCI patients with a history of depression, long-term SSRI treatment (>4 years) was significantly associated with a delayed progression to Alzheimer's dementia by approximately 3 years, compared with short-term SSRI treatment, treatment with other antidepressants, or no treatment and compared with MCI patients without a history of depression. No differences in CSF biomarker levels were observed between treatment groups.
CONCLUSIONS:
Long-term SSRI treatment may delay progression from MCI to Alzheimer's dementia.

[MarcR]

Despite the punchy title - "Impact" - this paper merely demonstrates association in a small (n=755), carefully curated subset of the all-volunteer Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. The full paper describes the intense selection bias and statistical wizardry required to tease out the conclusions - I recommend it to anyone inclined by the title and abstract to believe that SSRIs are good for cognitive health. (Incidentally, Sci-Hub continues to be available at sci-hub.bz, and I think the full text of this paper may be available by searching there for 10.1176/appi.ajp.2017.17040404.)

Related, ADNI is funded in large part by a constellation of companies that will benefit from increasing long-term use of drugs like SSRIs - "Araclon Biotech, BioClinica, Biogen Idec, Bristol-Myers Squibb, Eisai, Elan, Eli Lilly, EuroImmun, Hoffmann–La Roche and its affiliate Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research and Development, Medpace, Merck, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis, Pfizer, Piramal Imaging, Servier, Synarc, and Takeda".

[Orangeblossom]

Thanks for posting Julie. Interesting, to see in view of the other studies I linked to.

I can see how if depression might be linked in transfer to AD if both have low serotonin in common. From studies it does show that serotonin (and therefore SSRIs) promotes neurogenesis.

As SSRIs are not the only route to increasing serotonin (for example exercise, sun, eating foods rich in tryptophan, or 5HTP supplements from he seeds of an African plant known as Griffonia simplicifolia, or St John's Wort) possibly this might be something which may also help with AD...

Marc I wonder if any of these things may help your wife as she comes of her medication?

Serotonin is interesting as a neurotransmitter in the brain in itself and this discussion does not mean we need to solely focus on SSRIs. However I wanted to explain how they had helped me, as often medications can come across as 'bad' / vs more functional medicine as the 'good guy'. That is not always the case for some people and it is important not to demonise them or worry people who need them for their diagnosed mental health condition. They have been helpful for so many people and without some of the awful side effects of the older style medications.

I have been taking Prozac since 1999 (with breaks) and since then it has come off patent i noticed and now back to it's generic name, fluoxetine.

I will link to some natural sources to increase serotonin, in case anyone is interested. I wonder if any studies have been done on these and AD?

How to increase serotonin in the human brain without drugs https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/

https://www.marksdailyapple.com/serotonin-boosters/

It seems those of us taking fish oils maybe doing this already

"Not only does seafood provide ample amounts of the amino acid tryptophan, the long-chain omega-3 fatty acids found in marine fat increase serotonin production in the brain and improve serotonin transport across neurons.

You might take cod liver oil or eat the actual livers, as that provides both vitamin D (for increased tryptophan conversion) and long-chain omega-3s. However, a good daily dose of omega-3 supplementation through high potency, pharmaceutical-grade fish oil works fine, too, for those who get ample vitamin D otherwise."

In fact that article is quite in line with the other prevention advice for AD i think. It even mentions turmeric! I wondered why had been feeling better since starting it. Maybe that's how I've managed to cut down my prozac dose to every second day so easily. It is far better for me reducing it than coming off completely, and my doctors agree as it may prevent episodes on future.

[Orangeblossom]

I had a quick look to see if there were any studies about serotonin and preventing / mediating AD. and found some of interest.

In Vitro Effects of Serotonin, Melatonin and Other Related Indole Compounds on Amyloid β Kinetics and Neuroprotection. https://www.ncbi.nlm.nih.gov/pubmed/29131485

Serotonin: A New Hope in Alzheimer's Disease? https://www.ncbi.nlm.nih.gov/pubmed/26011650

Serotonin 6 receptor controls Alzheimer's disease and depression. https://www.ncbi.nlm.nih.gov/pubmed/26449188

[Orangeblossom]

Just to clarify how SSRIs' work- this is from the NHS site which explains-

It's thought that SSRIs work by increasing serotonin levels in the brain.

Serotonin is a neurotransmitter (a messenger chemical that carries signals between nerve cells in the brain). It's thought to have a good influence on mood, emotion and sleep.

After carrying a message, serotonin is usually reabsorbed by the nerve cells (known as "reuptake"). SSRIs work by blocking ("inhibiting") reuptake, meaning more serotonin is available to pass further messages between nearby nerve cells.

This is a a good article explaining how they may help depression by helping connection and nerve regeneration in the brain.

https://www.scientificamerican.com/arti ... epression/