Sure…work with your doctor or better yet, your naturopath since the doctor is probably the one who prescribed the SSRI after a 10 minute consult.
We did deep dives on SSRIs, the problem with them longer term, how SSRIs actually work.
Our experience with Lexapro was brutal (3 days of insomnia landing in the ER with serotonin syndrome) but coming off was even harder than getting off benzos (tips to get off benzos).
So…after deep dives (how we weaned off SSRIs), our key tips and takeaways!
A quick look at SSRIs, how they work, and the issues.
Here's the list:
- Go slow…work with your naturopath
- Tool #1 - CBD isolate
- Tool #2 - magnesium glycinate
- Tool #3 - steroidal hormones!!
- Tryptophan support
- Addressing what exhausts serotonin
- The problem with 5HTP and other supplements
- The first 30 days
- Unwinding trauma/infection (even early in life)
- Mushrooms, both medicinal and…psilocybin
Let's get started!
First, understand the enemy.
The SSRI lay of the land.
We'll stick to the bullet points but it's important to understand what you're replacing and how to support this change.
SSRIs boost available serotonin levels.
Serotonin is a master regulator of all human behavior with a focus on the following:
- Stress response
- Brain repair, growth, replenishment through downstream BDNF (the real star of the show)
- Sleep modulator (turns into melatonin)
- Pain threshold manager
- Self-esteem (yes! Even this is managed by serotonin)
Here's the issue with SSRIs briefly (lots of research here):
- They build tolerance - this means your natural level goes down with use (see tolerance)
- Levels can't be tested so we don't know if low serotonin is the cause
- Too much serotonin is brutal…even dangerous (see serotonin syndrome)
- Estimated to work for 30% of patients (generally very serious depression versus placebo)
The key takeaway is that stress, trauma, pain, and hyperactive immune response can exhaust serotonin.
We have to address that piece first or we're fiddling while our resilience burns. More on this below!
Okay…let's get into the tips. Some of these address the longer term root of serotonin exhaustion as well!
Go slow…work with your naturopath/doctor
It's not advisable to drop SSRIs cold turkey. Serotonin is just too powerful and if you've built tolerance, you have no safety net.
This can be excruciating. Serotonin isn't the "feel good" neurotransmitter.
It's more like the "feel right in your own skin" pathway.
A gradual approach is recommended by doctors and we used a pill cutter to slowly sliver off amounts over a 30 day window (at minimum). Adjust (more slowly) depending on how you feel.
Longer term use of SSRIs can really drive tolerance so it may be longer to rebalance serotonin assuming we address what was driving the underlying issue (more on that below).
Gradual wins the race.
Let's turn to tools that support this transition!
Tool #1 - CBD isolate
We have a deep dive on CBD versus SSRIs here.
CBD doesn't boost serotonin in one direction but works like a feedback mechanism…technically called an allosteric positive modulator.
Translation…support when low! That's why we don't see serotonin syndrome with CBD isolate.
One example of many:
Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Klingon translation…
After an injury (pain) exhausts serotonin and causes pain, anxiety, and inflammation, CBD would reverse this by supporting…serotonin!
5HT is code for serotonin.
Comparing CBD to an SSRI??:
Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST.
https://pubmed.ncbi.nlm.nih.gov/29885468/
FLX is fluoxetine (Prozac).
See CBD and depression or CBD and anxiety.
The key is that it doesn't build tolerance, cause addiction, or have bizarre side effects panel like SSRIs.
It was the heavy lifter for us in this process and how we found CBD to begin with.
We used this one; 300mg daily broken into 2 away from the SSRI by at least 4 hours. The 300mg matches research on BDNF, our brain's fertilizer and the real star behind SSRIs till the build tolerance.
More detail here.
Another key tool.
Tool #2 - magnesium glycinate
Mag is an amazing stress response buffer and coming off of SSRIs is a tremendous kind of stress….rattling the most powerful brain manager we have.
It's integral to calming activity via GABA (see GABA) and glutamate…the yin yang of brain excitability. This is part of its impact on mood, calm, and sleep.
Its interaction with serotonin is even more intimate:
Mg acts like a cofactor for tryptophan hydroxylase, intervenes in serotonin receptor binding in vitro and exhibits a direct enhancing effect on 5-HT1A serotonin receptor transmission
https://www.ncbi.nlm.nih.gov/books/NBK507250/
This means it's directly involved in the conversion of tryptophan to serotonin! tryptophan is fascinating for resilence.
There's even research on mag versus antidepressants.
Mag also has powerful effects on the pathway of serotonin directly:
One 2008 randomized clinical trial showed that Mg was as effective as the tricyclic antidepressant imipramine in treating MD.
https://www.ncbi.nlm.nih.gov/books/NBK507265/
Mag is awesome!
We take 100mg 3x's daily and as needed at night. The great thing? No tolerance. No addiction. We use this one here. The "ates" cross the blood brain barrier best.
It's a raw material that many people don't get enough of since our food's conveyor belt (soil bacteria/fungi) isn't working due to pesticides and mono-crop farming.
When we're stressed out, mag literally dumps out of the system via urine. Put it back in!
Let's get to the real culprit for many people…especially as we get older.
Tool #3 - steroidal hormones!!
Estrogen, progesterone, and testosterone are not just about reproduction.
Far from it!
You have receptors in every cell of your body AND brain for these powerful modulators.
Estrogen and Testosterone both drive serotonin. Point!
T drops about 1%/year for men starting around age 20. E plummets in a tailspin in the late 40s for women.
There goes serotonin and BDNF, the brain's fertilizer that offets the usual insults (trauma, stress, inflammation, etc).
Progesterone's no slouch as it drives GABA, our brain's brake pedal. If low, glutamate (the gas pedal) and inflammation literally degrade brain pathways and connections.
Serotonin gets exhausted. Anandamide (backup) can't keep up.
That's depression (and anxiety).
Look...loss of steroidal hormones may be a big reason many people are put on SSRIs to begin with!
Check out reviews of estrogen or testosterone and then ask why your doctor never checks your levels. You might get a little angry (and that's not the withdrawals!)
Work with your naturopath. Bioidentical (no synthetic) support as needed. We did deep dives on progesterone here and estrogen and mental health here.
T mirrors estrogen's effects (pro-growth and repair) since it's converted to estrogen by aromatase in the male brain.
Let's look at a basic precursor for serotonin.
Tryptophan support
Serotonin is made exclusively from the protein tryptophan.
In fact, when we're dealing with illness, our body will slow down tryptophan pathways to starve off the bacteria/virus which also needs tryptophan to make more of itself.
That's why mood can drop when we're sick…less serotonin!
We looked at that process here since low level infection can be tied to mental health.
We can support tryptophan pretty quickly with supplements. One note…it's not advisable to supplement if currently using SSRIs.
There's no tolerance or addiction risks with tryptophan by itself.
It's best to take tryptophan away from other proteins which can crowd out absorption.
Tryptophan is great before bed for sleep in this regard.
Those are a few immediate tools…both short term (mag, tryptophan, and CBD) and longer term (steroidal hormones).
We avoid the precursors like SAMe or 5htp since they can build tolerance albeit at a slower rate than SSRIs. It's tricky to monkey directly with such a powerful player as serotonin.
We use this one here. 1-5000 before bed is pretty impressive for sleep. Again, not with SSRIs.
Let's turn our attention to address why serotonin might be exhausted.
Addressing what exhausts serotonin
SSRIs are a band aid. One that sticks to the wound with time (tolerance).
Even the tools above help right the ship but it begs the question…why the depression or anxiety or insomnia to begin with?
Interestingly the tools above support:
- Stress response (cortisol, anandamide, and more)
- Repair and rebuild pathways (BDNF)
- Immune hyperactivity (inflammation)
The latter is really where the fascinating research is these days.
One example…
Glia cells are the immune sentinels in the brain but they do much more than just fight infection.
They literally manage the architecture of the brain!
Here's the issue…when hyperactivated, they literally spill out inflammatory assassins and…glutamate!
Yes, the brain's gas pedal which eats up GABA (target for benzos) and is toxic to brain tissue when too high.
Most (if not all) mental health issues show glutamate issues and inflammation at its core.
GABA is a short term, immediate buffer. Serotonin is the longer term buffer.
When both get exhausted, you have damage. Longer term, damage is mental health.
We looked at mental health broadly here but check out the immune system and mental health.
It's very exciting because we can actually unwind this damage and rebalance the immune system.
The newest studies on gut inflammation and probiotics (see probiotics for anxiety) shed light on this.
Fecal transplants from one set of patients (old, with Parkinson's, with anxiety, etc) to a health group can actually cause the symptoms to appear!
This is all about gut bacteria and it's a brand new world in terms of research. Ultimately, it's tied into inflammation states (again, back to the immune).
We'll touch on how to address that below.
Let's turn to some of the standard supplements on the market and why we shy away.
The problem with 5HTP and other supplements
We mentioned above that serotonin is a very powerful pathway, and it needs to be range bound.
Too much is just as bad as too little (maybe even worse).
There are supplements that can boost serotonin levels such as:
- 5HTP
- SAMe
- St. John's Wart
The problem is that these are agonists…they push in one direction. Hello, tolerance.
Granted, slower than SSRIs but still, we don't want to naturally deplete our baseline serotonin over time.
Tryptophan and Omega 3 oils are a better bet since they are raw materials…not agonists (boosters). See our big fats review. Eye-opening.
Some supplements are more nuanced but can also have issues.
Ashwagandha is billed as a hormone balancing supplement but its effects can be pronounced on serotonin with tolerance.
L-theanine is another supplement touted for anxiety. It's a green tea extract. Not that simple..
Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors.
https://pubmed.ncbi.nlm.nih.gov/17182482/
The bigger issue we see with herbs is histamine response. Histamine is excitatory in the brain and it's a sign the immune system is ramped up (hint hint).
Herbs can set off histamine responses which eat up GABA and then eventually serotonin.
This is a huge deal for women as they get older since progesterone is dropping and it's tasked with calming immune response (including histamine).
We see this with full spectrum CBD (lots of plant material) versus CBD isolate. Completely different response (more on that here).
There's actually very few tools we can use that don't build tolerance:
Let's turn practical.
The first 30 days
First…and we stress this…everyone's different. This is NOT a schedule for people.
It's just what we did base on research, and you should work with a naturopath.
Since it takes 30 days (at a minimum) for serotonin receptors to come back online after SSRI use, we looked at research on this initial withdrawal period.
First, we used a pill cutter to slowly reduce the level of the SSRI over 30 days.
Magnesium glycinate can be used right away (no interaction with SSRIs). We take 3 x 100mg daily. This is the one we use here. Great buffer longer term (no tolerance or cycling needed).
For CBD isolate, research points to higher levels with withdrawal but it might be the opposite with SSRIs.
We want to take CBD as far away from the SSRI as possible (at least 4 hours).
They both use the same liver pathway to process and CBD might make the SSRI last longer in the system as a result.
A test level is around 50mg daily and we ramped this up as we reduced the SSRI.
Peak neurogenesis (process of repair which relies on serotonin) is 300mg daily.
Going from 50mg daily to 300mg daily over a 10-20 day window reflects what we see in research. Everyone's chemistry is different so work with a naturopath and based on how you feel.
This matches research on opioid and alcohol withdrawal.
Tryptophan is great before bed but NOT WHILE taking SSRIs or medications that drive serotonin.
The other tools take three months to build (steroidal hormones, Vitamin D (yes...a steroid we get from the sun), NAC). Get tested for the hormones and work with a doctor. Make sure they're bioidentical.
The heavy lifter during this transition is really CBD since it directly supports serotonin when low. A safety net!
Learn more about CBD and serotonin.
Let's go one level deeper.
Unwinding trauma/infection (even early in life)
This is very exciting. Beyond the loss of steroidal hormones, early infection or trauma is probably the most significant factor we see in new research.
This can even happen in utero (especially in the 3rd trimester).
Why?
Early trauma/infection has the following effects later in life:
- Downregulating GABA (brain's brake pedal)
- Downregulating serotonin (ding ding ding)
- Downregulating acetylcholine (the calm and focus player)
- Upregulating brain inflammation
- Upregulating glutamat
Goodness. This is THE grab-bag of mental health and it primarily operates via changes to the immune system.
Big review on how this gets "recorded" in the immune system here and more importantly, how to erase it!
All the players above positively affect these imbalances. Some of these imbalances occur as hormones drop when we get older.
Check out our review of the immune system and mental health above but let's look at two huge tools here beyond what we mentioned above.
Mushrooms, both medicinal and…psilocybin
Mushrooms have powerful effects on our immune system, especially when out of balance.
We did a deep dive on medicinal mushrooms and psilocybin psilocybin.
Psilocybin (from magic mushrooms) will revolutionize mental health…especially with depression.
Newer research is showing that the longer term effects of psilocybin occur due to changes in immune system gene expression!
Thank you John Hopkins for leading the charge on this.
In our review of psilocybin and medicinal mushrooms, you can see the effects are primarily from the immune system and the real player is….wait for it….BDNF.
The medicinal mushroom are more varied with effects on gut inflammation, BDNF, neurotransmitters like GABA and serotonin, and more.
These are important tools to reverse the effects of early trauma/infection, stress, pain, and more.
Real healing. Not bandaids.
That's our top 10 tips for getting off of SSRIs while addressing the root issue as well. Check out the deep dive on the issues around SSRIs if you need further research.
Be well. Take care of each other. Take care of yourself.
More fascinating reviews:
Serotonin and resilience
Serotonin and self esteem
How SSRIs really work
Does CBD affect sex drive like SSRIs
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.