#1

Looks like there’s no general discussion on this, so I’m starting this one. But if I missed an existing topic, please merge this post there.

Depression seems to accelerate biological aging (see: Depression’s Unexpected Role in Accelerating Biological Aging ). In the US, 17.8% of adults are currently treated for depression:

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Depression is also a risk factor or even a prodromal symptom of many neurodegenerative diseases (NDDs) such as Alzheimer’s and Parkinson’s. It can start years or decades before the actual NDD diagnosis. As we improve prevention, early diagnosis, and treatment of cardiovascular diseases and cancer, NDDs are becoming the first cause of death in high-income countries.

Unfortunately, it looks like there’s no excellent treatment to date. Indeed, antidepressants seem, at best, a bit better than placebo (see: Antidepressant - Wikipedia). They’re also associated with significant withdrawal symptoms (see Antidepressant discontinuation syndrome - Wikipedia) that make me weary of just trying them. And some longitudinal studies also point to long-term risks:

(Although others show no risk, but no benefit either: Antidepressant use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study of potential adverse effects 2022)

As I have a family history of MDD and a personal history of low-mood episodes, I’d love to find ways to reduce my long-term risk of depression and associated complications (especially neurological damage), besides diet, sleep, exercise, meditation/stress management, and socializing, that are, of course, essential but, at least for me, not enough.

My reasoning is to look at “longevity interventions” (such as successful compounds in the ITP) and then, among them, look at those with antidepressive (and anti-anxiolytic) properties. I assume that they’re safe(r) for long-term use (on other markers of health than mental health) and that if they improve my mood they can be a reasonable long-term option. So far, I’ve found that:

Besides the above, I could not find anything. Either there are just a few weak papers on rodent models (but are animal models of depression good?) or small phase 1 or 2 trials on humans without strong conclusions. In any case, we rarely know the long-term effects of taking these drugs or supplements on general health (whereas we know that, for instance, long-term use of SGLT2 inhibitors is safe and even beneficial for some conditions such as CVD).

And then there’s ecstasy/MDMA (which will soon be FDA-approved for PTSD), psilocybin (approved in Australia and some Canadian provinces for depression) and other psychedelics. They’re interesting because they seem effective after just a couple of sessions, without withdrawal symptoms, compared to long-term use for traditional antidepressants, with a significant risk of discontinuation syndrome. But there are methodological weaknesses in psychedelic trials (the most important being the absence of a real blinded placebo: patients know for sure that they had the drug) and their safety profile is not yet fully known. They also seem to work as part of a “psychedelic-assisted therapy”. So I would not try them alone but I would prefer to do it under the guidance of an experienced therapist. And unfortunately, they’re not yet approved where I live (the UK, although ketamine is approved here). I could travel to places where it is approved (or just tolerated, like Portugal) but I would prefer something local.

What do you think? What do folks here use or have tried? What’s the state of the research on this topic? Are there other promising interventions?

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#2

Good topic.

My most successful mood management device is exercise. Being outdoors is a big one (NIR, beauty, fun, curiosity). Being with a dog makes a big difference. Being with or talking to a good friend about anything. Now I also use regular (20 minutes a day) deep breathing.

I’ve used these supplements with success:
Lithium orotate — current
St John Wort — past

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#3

Thanks. I indeed forgot to mention low-dose lithium (~1mg/d) which seems effective for depression, safe for long-term use, and with beneficial effects beyond depression (and anecdotally, I also see positive effects when taking it, but it’s blunted by SGLT2 inhibitors): Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation - PubMed

Devices such as transcranial Direct Current Stimulation also seem safe and effective but mostly for acute major depressive episodes. And they may not have effects beyond that: Transcranial direct-current stimulation - Wikipedia

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#4

I hesitate to mention it but I have found that a short period of high pain will bring a subsequent period of mental peace. Of course I don’t mean intolerable pain but rather things like deep tissue massage, a lacrosse ball on a “knot”, a vo2max test, sustained muscle “lactate” burning (not really lactate).

There is a pressure point between the thumb and index finger that can be used to create harmless pain for this purpose or just to stay alert when sleepy. I used it to stay awake in early morning College classes. Hold finger straight…press thumb against hand…use other hand to press at bottom of crease between thumb and hand.

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#5

I had depression, sometimes bad, for most of my life since high school. After I started using the SPERTI light for vitamin D it went away. It’s been years with no problem. I use a red light (Platinum) also at the same time, but doubt that is it.

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#6

Awesome. I want one of those lamps.

#7

Just published: “UCSF’s Ellen Bradley has a theory that neurodegeneration in Parkinson’s is caused by a lack of neuroplasticity. Because psychedelics increase synaptic activity, she’s studying psilocybin as a treatment for people with early stages of Parkinson’s.” (tweet, article)

Ellen Bradley is running a phase 2 trial of psilocybin in Parkinson’s, with results expected next year.

Another team at Johns Hopkins University is running a phase 1 trial of psilocybin in Alzheimer’s, results are also expected in 2025.

So next year we’ll hopefully know whether psilocybin is neuroprotective or not.

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#8

Also following psilocybin - looking forward for more research / considering microdosing or retreat.

Personal experience in decreasing order of impact:

  • mindfulness training - it can reduce depression substantially;
  • good cardio session: works well against any kind of mental issues;
  • NAC: reducing anxiety;
  • lions mane / reishi - works also against depression and improoving mood;
  • ashwagandha: works against depression / improve sleep.
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#9

Right now only statins which are associated with improved mood.

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#10

I really love your posts @adssx

My addition to it is checking for nutrient deficiencies. Folate (RBC test), B12 (MMA test), Vitamin D, magnesium (RBC test), etc deficiencies can all be linked to depression

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#11

Light exposure early morning and middle of the day especially in the winter half of the year or overcast days, but ideally year around.

Ideally natural light outdoors.

I felt this was so important that it factored into my decision to move from a cold, dark winter place to a warm, much brighter/sunnier place where it seldom rains.

But I also implement with artificial lights at those times of the day at high levels and also with light directed at the receptors in the ears when I feel I need it extra.

I have an earlier version of this

https://humancharger.com/

Ownership / company might have changed, before they referred to a whole range of papers out of one of Finland’s universities.

See also

Might also want a whole face light box:

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#12

sorry if I missed/am forgetting, could provide more color on this

is it just blunting or is there a negative interaction of some sort?

#13

I also found this helpful (and something that be done while reading, winding down with my wife and just talking, listening to an audio book, etc)

Saw it in Bryan Johnson’s stack.

In Europe you can also get

That has more published scientific studies I think

Both has discount codes on the Blueprint Protocol webpage

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#14

Another device for depression… not sure of the science behind it, or validation of the approach.

NHS trials £400 headset to treat depression

The device, called Flow, uses transcranial direct current stimulation (tDCS) to target the physical causes of depression.

It is currently being trialled on around 200 NHS patients. If those trials are a success, manufacturers hope it will be widely available across the NHS within five years.

But the company behind it, Swedish firm Flow Neuroscience, said that in the absence of NHS availability, a significant number of people are choosing to buy the £399 Flow headset out of their own pocket.

There have now been nearly 20,000 private sales of Flow across the UK and Europe since its launch in the UK in 2019. Between December 2022 and December 2023, the company said there was a near-700 per cent increase in new patients ordering the device.

História completa: https://archive.ph/eURj7#selection-1129.0-1145.250

The Company and Website:

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#15

NHS backing is promising.

Also

Double-blinded, placebo-controlled clinical trial, UK/US (n=173)

Looks like scientists at top institutions are publicly intrigued and excited about the clinical trial results

You can read the pre-print here, the full paper will be available in early 2024.

Will be interesting to see where the paper comes out after peer review.

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#16

Thanks :hugs: I love this community, learning new things every day with nice people all aligned with the same goal of helping each other and being healthier together. I’m grateful to have found this forum!

Starting empagliflozin or dapagliflozin in patients on lithium? Monitor lithium levels

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin and dapagliflozin, may increase the renal excretion of lithium and lead to decreased serum lithium levels. Monitor the patient’s serum lithium levels more frequently when a SGLT2 inhibitor is initiated or following dose changes. Adjust the lithium dose if necessary.

So, I understand that you may have to increase your lithium intake?

I have the Nurosym device. I did not see any meaningful improvement so I stopped using it. The research around vagus nerve stimulation is also inconclusive so far:

According to this paper: “The effect of the vagal nerve stimulation on cognition and memory depends on stimulation protocols.” ( Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders 2020)

So there’s probably an optimal Hz, current, eat, frequency of use, etc. to achieve the desired results. And this optimal protocol may not be identical for all individuals. And could it be that suboptimal tVNS use is actually detrimental? I don’t know, not enough research, no clear benefits while testing, and you can stimulate your vagus nerve in ways that seem safer to me, and as effective, if not more, such as cold exposure, deep and slow breathing, singing, meditation, exercise, massage, socializing and laughing: 19 Factors That May Stimulate Your Vagus Nerve Naturally

Yes it’s the transcranial direct-current stimulation (tDCS) that I mentioned yesterday. (Like tVNS, it’s a form of neuromodulation) It’s proven effective for acute episodes of major depression. But it’s unclear whether it’s effective for long-term treatment-resistant depression. And it does not seem to improve cognitive performance in healthy people, Alzheimer’s patients, schizophrenia patients, or Parkinson’s patients: Transcranial direct-current stimulation - Wikipedia

Anyway, the more I read about this Flow device the more I want to try it. The reviews are amazing: Flow Neuroscience Reviews | Read Customer Service Reviews of flowneuroscience.com I’ll let you know if I buy it… (my fiancée already thinks I’m a weirdo with the red light therapy, if I start walking around at home with that thing on my head I think I’m a dead man :sweat_smile: )

From their website:

Can you fit Flow into your daily life?
Flow is used for 30 minutes a day, 5 days a week for the first 3 weeks. This is the activation phase which activates the neural network.
It then drops to 2 days a week. This is the strengthening phase which supports the progress made in the activation phase.
You can do other things while using Flow - replying to emails, eating dinner, meditating.

The results of their trial are not impressive though, even though their device does better than placebo (“sham”), the placebo effect accounts for most of the improvement over the 10w period: Home-based transcranial direct current stimulation RCT in major depression

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I’d like to see results over a longer period of time, at least 1 year. Ideally, I’d like to see sham device users returning to baseline after a few months while Flow users keep improving.

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#17

Moderate morning exercise, including about 20 minutes’ walk among the trees (I have a quarter mile trail in back yard). I enjoy the birds and open sky. Over the day average 5 to 7 miles walking, mostly outdoors. Missing this routine has a clear negative effect. Topping off a more vigorous exercise routine with a cold shower is good - sets me more up for many hours, but not something I do daily. A good book. Eating well and not too much. On days when I’ve done a bit more time restricted eating in combo with eating less I’m more mentally at ease yet alert. No human companions at home, so having my dog certainly helps. I’ve read that omega-3 intake helps, which I take, but cannot gauge effect. Same with Li. Overall, exercise, good diet, time outside, and a routine which also minimizes running down senseless negative and time-wasting rabbit holes helps me maintain.

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#18

I understand that thinking about antidepressant treatment isn’t someone’s first choice, but for some people they do work and work well. I am one of those people. I have severe GAD and have been on fluoxetine for over 20 years without any major issues. Without it, I was/would be unable to function. It might not be ideal as a prophylactic, but I would definitely not discount the entire class of medicines, at least for depressive episodes, just because there are some negative associations.

Side notes:

  • Some forms of treatment-resistant depression have improved with use of amphetamine.

  • Sleep restriction may alleviate depression temporarily in some people. In fact, I had a depressive episode in the early 2000’s that did markedly improve with lack of sleep. This is obviously not a long-term intervention, but it is interesting nonetheless.

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#19

@melivelongtime Yes and yes. I have found Adderall to be a good mood elevator, and it almost lasts all day. Likewise with the occasional use of sleep deprivation. I once had a job with deadlines and often to meet them I had to pull all-nighters. After struggling and getting nowhere for hours, I usually did my best work at dawn. I found myself in a flow state and the work became nearly effortless.

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#20

The rapamycin+ketamine data is very interesting, especially since some preclinical work indicated that ketamine’s antidepressant/AD effects required mTOR. One of that paper’s authors has suggested that rapamycin may inhibit microglial synaptic pruning, and that this may prolong a ketamine-mediated increase in synaptic density.

It’s also interesting that preclinical work suggests ketamine’s AD effects require GSK3β inhibition [1], and lithium can even potentiate ketamine’s AD effects in mice. [2] Interestingly enough, GSK3β’s cellular localization is governed by mTORC1, and rapamycin partially redistributes GSK3β to the nucleus. [3]

Big drawbacks with ketamine it can be extremely addictive, it’s clearly toxic to the bladder, and is acutely cognitive impairing.

1 Like