Antidepressants – Seeking Experiences and Recommendations

[johann1]

Goal
Assistance in selecting a suitable antidepressant for a good friend facing complex health challenges. There is a psychiatrist appointment upcoming, this is just for preparation.

Background
A good friend has been taking antidepressants for many years to treat the following conditions:

• Painful SFPN
• POTS
• ADHD
• Impulse control disorders
• Binge eating
• Obsessive-compulsive disorder
• Depression
• cPTSD
• Anxiety disorder
• Sleep disorder

Previous Experiences

• Fluoxetine: Long-term use, but discontinued 6 weeks ago due to a serotonin syndrome (likely caused by a drug interaction).
• Psilocybin: Tried, but led to a severe crash with strong side effects.
• Sertraline: Prescribed by her psychiatrist, but had to be stopped immediately due to urinary retention.

Known Intolerances

• Mirtazapine
• Certain antipsychotics, ADHD medications, and antihistamines

Specific Health Conditions

• ME/CFS
• SFPN
• POTS
• Heart valve insufficiency (mild mitral valve insufficiency, moderate tricuspid valve insufficiency, sinus tachycardia)
• MCS
• MCAS
• Hereditary thrombophilia
• Fibromyalgia
• Prediabetes type 2
• Gastroparesis

Genetic Particularities

• CYP2C19: Reduced (heterozygous) enzyme activity – slowed metabolism of many psychotropic drugs.
• NAT2: Reduced enzyme activity (genotype 5/5) – slowed metabolism of various medications, including some antidepressants and antipsychotics.

The multitude of conditions and possible interactions (especially within the serotonergic, cholinergic, and catecholaminergic systems, as well as concerning the heart, kidneys, liver, and MCAS) makes the choice of medication very risky. Strong discontinuation symptoms have also been observed in the past.
Many candidates are ruled out immediately.

Given that strong discontinuation symptoms are also present (and in an attempt over several months a few years ago, the withdrawal symptoms always persisted), it is questionable whether only an SSRI is an option, or perhaps another group should be considered.

Candidates Considered So Far:

• SSRI Fluoxetine / Prozac:
  • Positive: Long-term experience suggests it is generally well-suited.
  • Question: Is reintroduction advisable?
• SSRI Fluvoxamine / Luvox:
  • Positive: Generally a good candidate.
  • Downside: Production was allegedly discontinued around the turn of the year.
• Atypical Bupropion / Wellbutrin:
  • Positive: Many anecdotal positive experiences.
  • Concern: Possibly overstimulates the catecholaminergic system, thereby increasing the risk of crashes.
• Melatonergic Agomelatine:
  • Positive: Potentially very good, especially for sleep issues.
  • Downside: May be too weak for other symptoms.
• Atypical Vortioxetine / Brintellix:
  • Positive: A very good candidate.
  • Downside: No longer available in Germany – might have to be sourced from abroad.

Questions for You:

• What experiences have you had with these or similar antidepressants?
• Which candidates would you recommend or advise against – particularly in view of the aforementioned health conditions and genetic factors?
• Are there alternative approaches or medication recommendations that you have tried in such complex cases?

 

[Mary]

@johann1 - I don't do well with prescription anti-depressants but do just fine with 5-htp, 5-htp is derived from tryptophan, and helps produce serotonin. And it does not have the many bad "side" effects of prescription anti-depressants. I started taking it some 20 years ago to help with sleep.

5-htp is cheaper than tryptophan and crosses the blood-brain barrier more easily too. I take 100 mg. 5-htp at night before bed.

 

[johann1]

Thank you, I'm happy it works for you.
Unfortunately she has already tried that years ago, but had to stop because auf some side effect. Thx nevertheless

 

[katabasis]

@johann1 - I don't do well with prescription anti-depressants but do just fine with 5-htp, 5-htp is derived from tryptophan, and helps produce serotonin. And it does not have the many bad "side" effects of prescription anti-depressants. I started taking it some 20 years ago to help with sleep.

5-htp is cheaper than tryptophan and crosses the blood-brain barrier more easily too. I take 100 mg. 5-htp at night before bed.

You should know that 5-HTP is thought to increase the risk of cardiac valve fibrosis - a lot of it is metabolized peripherally, and the resulting serotonin is an agonist at 5-HT2B receptors on the heart. The exact extent of this risk a bit unclear, but it seems especially pertinent to OP since they mentioned heart valve insufficiency. Fortunately, there is a way to prevent this peripheral metabolism - EGCG blocks this enzyme, and it's usually a pretty well tolerated supplement. It's derived from green tea, and you might even be able to get enough EGCG from drinking green tea every day to mitigate the risks of 5-HTP.

Fluoxetine: Long-term use, but discontinued 6 weeks ago due to a serotonin syndrome (likely caused by a drug interaction).

If you don't mind, could you elaborate on the serotonin syndrome incident? In my experience, people often mistake other acute syndromes (or even just normal-ish drug side effects) for serotonin syndrome, which is actually not all that common. I'm not saying this is necessarily the case for you, but even if it were serotonin syndrome, if you can identify what triggered it and this trigger can be avoided, it seems a shame to have to discontinue a drug that seems to have been working fairly well otherwise (I'm assuming, based on the fact that it was long-term use).

Which candidates would you recommend or advise against – particularly in view of the aforementioned health conditions and genetic factors?

One thing I'd point out is that a lot of tricyclic antidepressants have anticholinergic side effects. In some cases, these can be beneficial in depression (for instance) as they can help disinhibit dopamine release, and also cause a little sedation which may help agitation or insomnia. But acetylcholine is one of the primary neurotransmitters of the autonomic nervous system, so in someone who has SFPN, POTS, and gastroparesis, tricyclics could be potentially harmful. It looks you don't have any on your candidate list, but I thought I'd mention this just in case.

Aside from the SERT-selective anti-depressants, a supplement worth trying might be N-Acetyl Cysteine. Its similarity to dietary cysteine (a common amino acid) means it's usually fairly well tolerated, and it's shown to be helpful in both OCD and ADHD, as well as potentially having benefits in ME/CFS and long COVID (there's a study where it's coadministered with guanfacine, if you want to look into this).

For the depression, cPTSD, anxiety, and potentially even for the SFN, have you considered ketamine? It's pretty easy to get nowadays in the USA - I'm not sure about Germany but a quick google shows at least theoretically it can be prescribed there for depression. Having failed other antidepressants would probably help you get access to it. Ketamine can be a bit of an "experience" (to say the least), not something to take lightly, but on the upside, the actual drug duration is fairly short despite long lasting benefits. So even if there are side effects or the experience is unpleasant they might be more tolerable as an occasional thing.

 

[johann1]

If you don't mind, could you elaborate on the serotonin syndrome incident?

As far as i remember it was

• tremors
• tachycardia
• agitation

But i'm sure the list isn't comprehensive. The trial of Rhodiola Rosea was, what triggered it (as far as i remember). The fear was and is, that after year long use, she might have developed a sponatenous intolerance to it (has happened before for other medications). But she is aktually considering going back to it.

One thing I'd point out is that a lot of tricyclic antidepressants have anticholinergic side effects.

Yeah, that's why they aren't considered. Thanks for your pointers.

a supplement worth trying might be N-Acetyl Cysteine

I do think she takes that already, or at least has, because i think i saw it in her fridge (N-Acetyl-L-Cystein). If i remember correctly, she spoke of it as immunemodulating and detoxification; but i haven't had it on my radra as antidepressant. I'll ask her later about it.
And i'll look into the study, i think you could mean Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19” - ScienceDirect.
I also found Combined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury - PMC, which points in a similar direction. At first glance i'm a little concerned the possible blood pressure lowering effect.
(a little off-topic, but i do have N-acetyl-L-leucine: a promising treatment option for traumatic brain injury - PMC on my radar for it's possible use case in me/cfs,; seems to go into a similar direction )

For the depression, cPTSD, anxiety, and potentially even for the SFN, have you considered ketamine?

Thank you! Actually it is considered, as there is a treatment center combinig it with rTMS or tDCS for cPTSD treatment (something like a 2 week "retreat"). I'll have to up it on the priority list, thank your for the reminder!

 

[Wayne]

• Obsessive-compulsive disorder

A few years ago, I ran across a remarkable article on OCD, and how a researcher in Israel discovered that inositol can often dramatically improve OCD symptoms. I take it regularly, and find it has a nice calming effect. Here's a link in case you might want to check it out: -- LISTENING TO INOSITOL: CLINICAL NOTES

 

[katabasis]

As far as i remember it was

• tremors
• tachycardia
• agitation

But i'm sure the list isn't comprehensive. The trial of Rhodiola Rosea was, what triggered it (as far as i remember). The fear was and is, that after year long use, she might have developed a sponatenous intolerance to it (has happened before for other medications). But she is aktually considering going back to it.

If those were the main symptoms, it wasn't necessarily serotonin syndrome, or at least not severe serotonin syndrome. Usually, the reason serotonin syndrome is dangerous is due to a very high fever or due to severe rigidity or seizures which can result in rhabdomyolysis. And without those symptoms, making the diagnosis is a bit less obvious.

The SSRI + Rhodiola combo certainly *could* cause serotonin syndrome, but Rhodiola is a pretty weak MAOI, and those symptoms could also be entirely psychiatric, neurological, or even endocrine in nature - due to elevated norepinephrine, or the HPA axis effects Rhodiola has, for instance. I'd advise against the combination of those drugs, obviously, but going back on fluoxetine seems pretty reasonable. I'm no fan of SSRIs, but if they work, then they work. And while she could have developed an intolerance to fluoxetine due to the ME/CFS (not too uncommon), this seems like a separate issue entirely, not related to serotonin syndrome.

Separately, yes, those were the NAC articles I was thinking of. NAC can lower blood pressure but AFAIK this is more common in people who already have hypertension, because NAC can reduce oxidative stress and improve insulin sensitivity (both factors in hypertension). If it's a concern, I'd recommend starting with a low dose and monitoring blood pressure as you go.

 

[Blazer95]

if the serotonine syndro was caused not by fluoxetine alone but by interaction it could be reintroduced + staying on a lower dosage.

serotonin-syndrom is no joke and has to be treated seriously, but when its clearly an interaction this option still is there.

also i want to say that i have good experiences with citalopram. since it modulates the immune system in many ways i turned out to become moderate by using citalopram. i am now able to live alone and work 1 hour daily wich is crazy considering i used to lay in bed most of the day in fight or flight and constant pain.

you should take into consideration though that ssri CAN make gastroparesis worse. for me for example it did. i had to change my diet and introduce another drug to counteract the delayed gastric emptying caused by citalopram, but for me it was worth it considering the heavy increase of function i have gained from it.

if you have more questions feel free to ask i have been taking citalopram for almost a year now

 

[Scarlett*54]

Goal
Assistance in selecting a suitable antidepressant for a good friend facing complex health challenges. There is a psychiatrist appointment upcoming, this is just for preparation.

Background
A good friend has been taking antidepressants for many years to treat the following conditions:

• Painful SFPN
• POTS
• ADHD
• Impulse control disorders
• Binge eating
• Obsessive-compulsive disorder
• Depression
• cPTSD
• Anxiety disorder
• Sleep disorder

Previous Experiences

• Fluoxetine: Long-term use, but discontinued 6 weeks ago due to a serotonin syndrome (likely caused by a drug interaction).
• Psilocybin: Tried, but led to a severe crash with strong side effects.
• Sertraline: Prescribed by her psychiatrist, but had to be stopped immediately due to urinary retention.

Known Intolerances

• Mirtazapine
• Certain antipsychotics, ADHD medications, and antihistamines

Specific Health Conditions

• ME/CFS
• SFPN
• POTS
• Heart valve insufficiency (mild mitral valve insufficiency, moderate tricuspid valve insufficiency, sinus tachycardia)
• MCS
• MCAS
• Hereditary thrombophilia
• Fibromyalgia
• Prediabetes type 2
• Gastroparesis

Genetic Particularities

• CYP2C19: Reduced (heterozygous) enzyme activity – slowed metabolism of many psychotropic drugs.
• NAT2: Reduced enzyme activity (genotype 5/5) – slowed metabolism of various medications, including some antidepressants and antipsychotics.

The multitude of conditions and possible interactions (especially within the serotonergic, cholinergic, and catecholaminergic systems, as well as concerning the heart, kidneys, liver, and MCAS) makes the choice of medication very risky. Strong discontinuation symptoms have also been observed in the past.
Many candidates are ruled out immediately.

Given that strong discontinuation symptoms are also present (and in an attempt over several months a few years ago, the withdrawal symptoms always persisted), it is questionable whether only an SSRI is an option, or perhaps another group should be considered.

Candidates Considered So Far:

• SSRI Fluoxetine / Prozac:
  • Positive: Long-term experience suggests it is generally well-suited.
  • Question: Is reintroduction advisable?
• SSRI Fluvoxamine / Luvox:
  • Positive: Generally a good candidate.
  • Downside: Production was allegedly discontinued around the turn of the year.
• Atypical Bupropion / Wellbutrin:
  • Positive: Many anecdotal positive experiences.
  • Concern: Possibly overstimulates the catecholaminergic system, thereby increasing the risk of crashes.
• Melatonergic Agomelatine:
  • Positive: Potentially very good, especially for sleep issues.
  • Downside: May be too weak for other symptoms.
• Atypical Vortioxetine / Brintellix:
  • Positive: A very good candidate.
  • Downside: No longer available in Germany – might have to be sourced from abroad.

Questions for You:

• What experiences have you had with these or similar antidepressants?
• Which candidates would you recommend or advise against – particularly in view of the aforementioned health conditions and genetic factors?
• Are there alternative approaches or medication recommendations that you have tried in such complex cases?

My question is what is the underlying cause of these specific health conditions? The reason I ask is because I, too, have many of the same conditions & have taken many antidepressants over the years. It wasn't until I addressed & got help for the traumas in my life (both in childhood & adulthood) that I began to heal.
The books that really changed my life was The Myth of Normal & When the Body Says No, both by Dr. Gabor Mate. He addresses illnesses in a holistic (mind/body) in a way that Western (pharmaceutical-based) does not. For what it's worth, this helped me discover a whole new path to healing. I found a good holistic doctor & a good therapist. (I don't want to make it sound quick & easy because it wasn't)!

I wish you and your friend all the best on your healing journey.

 

[johann1]

If those were the main symptoms, it wasn't necessarily serotonin syndrome, or at least not severe serotonin syndrome. Usually, the reason serotonin syndrome is dangerous is due to a very high fever or due to severe rigidity or seizures which can result in rhabdomyolysis. And without those symptoms, making the diagnosis is a bit less obvious.

Additionaly stiffness and fever.

My question is what is the underlying cause of these specific health conditions?

Well, cause and effect is the real bugger to find out. Thanks for your input.

 

[GhostGum]

I was just in this big annoying discussion on social media today about the issue with anti-depressants and the issues with getting off of them. But I referred them to a professional who had his own drama's with psych meds but then went on to study and redefine the issues around them and proper tapering protocols,

https://markhorowitz.org/

I am guessing the person you are referring to is the same person who posted here just recently. I pointed out already long term anti-depressants requires a very slow taper, according to Mark you are looking at 10% decreases monthly. He himself spent years tapering off different meds. So quite simply the difficulties your friend is having likely have to do with coming off the meds too quickly.

But of course it is not always easy to asses these things when there is different things going on. It is also possible like some of us here, myself included, that there can be specific genes at play and too slow a break down of certain things, like different neurotransmitters which complicate things.

You should check out Mark's work though and even the book, it might be helpful in understanding what is going on. Not even sure most psychiatrists are up to date on this stuff, quite often they will just default to the patients mental health issues and recommend more meds.

 

[GhostGum]

Sorry I should correct something here, that the genetic comment is a bit random and if someone has slow neurotransmitter break down they likely could not use SSRI's in the first place, it is probably not that relevant and unless you know a persons actual SNP's. I actually think I get mild serotonin syndrome on and off naturally due to my makeup and realised years ago I should stay the hell away from SSRI's.

Hope your friend is doing alright johann and in not too bad a situation, but getting off a long term drug like that without even a half decent taper can literally be hell.

​

 

[Wayne]

Mad with Medication: A New View on Psychiatric Drugs
BY FULL MEASURE STAFF SUNDAY, MARCH 17TH 2019

The above is a link to a 5-Min. segment featuring an interview with a Psychiatrist who's never prescribed a drug for his patients, but has spent a great deal of time helping those who have become dependent on psychiatric drugs get off of them. He also wrote a book entitled, "Psychiatric Drug Withdrawal". It's the only book written on the topic.

In the video segment, the author describes the approval process for Prozac, which he became aware of when he was appointed to the discovery process by the U.S. government as part of a lawsuit against Eli Lily. He relates how the lead investigator discovered during the approval process of Prozac that it was filled with "addictive sedatives".

It also was discovered to have "amphetamine type" qualities, which could make depression worse, make people agitated, angry, more prone to suicide, etc. The interview paints a rather unflattering picture of the Psychiatric and Pharmaceutical Drug professions, which often work in collusion with the FDA to approve drugs without adequate warning about how much harm they can cause.

What many people don't know is that antidepressants can cause permanent tinnitus. Below is a testimonial from a tinnitus forum, which is one of many on that forum. (at THIS LINK)

So in October my doc took me off that antidepressant and prescribed Prozac and Ativan. Instantly my ears began to ring. I contacted my doc and he told me this can be a temporary side affect of the Prozac. He instructed me to try 2 more weeks on the Prozac and discontinue if it persisted. It did, so I stopped taking it. But the tinnitus never stopped.

It's been 3 months since stopping the Prozac and the tinnitus continues. I still take a very low dose of Valium for anxiety and have some depression. My life has been completely changed. I went from being a very happy and productive member of society to depressed, anxious, and dealing with tinnitus.