My first real l-methylfolate case

[Lindaroo]

That's great! I'm glad that worked out for you.
What financial interest does Dr. Farah have with Enlyte?

I thought about that also. The only reason I mentioned Dr. Farah is because I thought his credentials would mean something to other professionals. The initial question I had back in May was regarding a request for any further legitimate information about this topic, trying to avoid anyone trying to sell something. I was thrilled to see Former Jolly Good Fellow's post while searching on Google Scholar, because his patient had a story similar to mine.
My sister's doctor ordered the MTHFR test for her back in June after hearing my story and seeing my test results. My sis has the same two mutations. Her story of lifelong depression is also like mine. Her response has been good but not as robust as mine to the L-methylfolate. Who knows why? For her, it's adjunctive but now her SSRI works.
We also have two other siblings who are schizophrenic and we are wondering if this will help them also. Needless to say, our family just wants more quality information, and as this thread is showing, the debate continues. We want to avoid as much junk science as possible and just keep asking in hopes of finding out more.

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[Lindaroo]

well he's on their website
and has accepted $249k of blood money between 2013-2016 mainly for abilify

Thanks for that bit of information. That is a bit discouraging and just muddies the water for those of us just wanting unbiased info...

 

[Tmcc]

I thought about that also. The only reason I mentioned Dr. Farah is because I thought his credentials would mean something to other professionals. The initial question I had back in May was regarding a request for any further legitimate information about this topic, trying to avoid anyone trying to sell something. I was thrilled to see Former Jolly Good Fellow's post while searching on Google Scholar, because his patient had a story similar to mine.
My sister's doctor ordered the MTHFR test for her back in June after hearing my story and seeing my test results. My sis has the same two mutations. Her story of lifelong depression is also like mine. Her response has been good but not as robust as mine to the L-methylfolate. Who knows why? For her, it's adjunctive but now her SSRI works.
We also have two other siblings who are schizophrenic and we are wondering if this will help them also. Needless to say, our family just wants more quality information, and as this thread is showing, the debate continues. We want to avoid as much junk science as possible and just keep asking in hopes of finding out more.

There is some interesting research out of MGH Boston regarding Schizophrenia and L-Methylfolate. Look up Joshua Roffman, MD.

 

[Tmcc]

I'm beginning to wonder just how many trolls we're feeding here...

Lindaro is probably a drug rep also.

 

[Lindaroo]

I'm not a rep and I am not selling anything.
What I am requesting is where to look for further, legitimate information, websites, resources (no sites selling supplements, puhleease) and to hear more from those who've had experience-in-practice on the topic of MTHFR gene mutations, depression, schizophrenia and L-methylfolate. It is so controversial and yet I have the undeniable, very similar experience as Former Jolly Good Fellow's patient, so I know there is something to this.
I could care less what product brand is involved. I have two family members who have suffered the extreme burden of almost life-long schizophrenia (one with childhood onset and one with teen onset), in addition to the other three of us with treatment-resistant depression.
I think it's worth a try to ask for information from medical professionals dedicated to education and science, and hopefully get further info to alleviate suffering for not just my family but others I've met who have been treatment-resistant.

 

[Lindaroo]

Lindaro is probably a drug rep also.

I'm not a drug rep and I am not selling anything whatsoever.

 

[Lindaroo]

There is some interesting research out of MGH Boston regarding Schizophrenia and L-Methylfolate. Look up Joshua Roffman, MD.

I just looked up his info on the MGH site and I truly appreciate it!

 

[whopper]

I've done pharmacogenetic testing quite a few times as of this writing. I also used to work at the Lindner Center, a place where the testing was first offered (it's right outside of Cincinnati and Cincinnati is where they first tested the Genesight test).

While at Lindner I never saw major results but at that time I've only seen it done on a handful of patients. That was a few years ago and since then the test has been improved upon. Also back in the day, a lot of patients there have beeg money and wanted the test but might've not have met treatment-resistance guidelines.

I've since done it several times because there's better guidelines on insurance paying for it.

It's not 100% accurate, but I have noticed better results with pharmacogenetic testing than not with antidepressants. I also find almost no benefit with using it for antipsychotics. If you look at the data the company gives showing it's benefits, most of it is for antidepressants.

After doing the test several times, it makes sense. With the exception of Trintellix they all have about the same efficacy, so anything that can tip a scale that is otherwise perfectly balanced can lead validly in one direction where with antipsychotics it's different. CATIE clearly showed that some are clearly more efficacious than others. So on a scale that already is heavily tipped for Clozapine and Olanzapine, and the gene data tips against it somewhat, it still doesn't rule out those antipsychotics. (By no means am I trying to push Trintellix. That med is freaking expensive and it's not much more efficacious!)

The gene data showing, for example that Clozapine might not work well is slightly pushing a scale heavily tipped for Clozapine. I wouldn't use pharmacogenetic testing at this point to rule against use of Clozapine especially since medical science isn't exactly sure why Clozapine is more efficacious.

I've also noticed that the patients I've done the testing on, who have failed a few antidepressants pretty much all had the gene that makes SSRIs not as efficacious (I didn't double check off-hand which one but I believe it's the SLC6A4). What usually happened is either another psychiatrist or I tried 1-2 SSRIs. This also explains why when 2 SSRIs have been tried an failed the odds actually go up than an SNRI will work, and will significantly lower the odds another SSRI will not work.

 

[hamstergang]

If you look at the data the company gives showing it's benefits, most of it is for antidepressants.

Has pharmacogenomic testing been studied even for any condition other than depression? I believe the answer is no, and yet the companies include data for several other types of meds anyway.

 

[whopper]

The difference between these salt form molecules is that a crystalline salt molecule is more stable, whereas an amorphous salt molecule is less stable. What does this mean to you or me? It means that if the amorphous ingredient is manufactured 12 months before use, it can lose up to 16%+ of its potency, compared to a crystalline form, which will only lose 1-2% of its potency.
Deplin contains Metafolin and is a Medical food FDA regulated with several studies. Methylpro is a supplement with no studies hence the $25 price.

Thanks and I wasn't aware of this. At this time I don't see a major difference between the two but the above tells me if they take Methylpro they should just make sure they use it within months of purchase.

At this point I've now had dozens of patients improve with L-Methylfolate. The data is hard, real and published that it works as an augmentation for antidepressants. The real question IMHO for clinicians is should we be ordering MTHFR gene tests? They are expensive, often times not covered by insurance, and while it's highly possible the gene test would be helpful I don't know if it's worth it given that L-Methyfolate could work anyways to treat depression as an augmentation agent even if they don't have the mutation.

I suspect that if you have the mutation L-Methyfolate's odds will increase in being effective. In fact of the dozens of patients I've treated people with the double mutation seem to have a much more serious history of depression but this has not been validated yet in studies. IMHO this is a gold-mine area of possible future research.

 

[whopper]

Has pharmacogenomic testing been studied even for any condition other than depression? I believe the answer is no, and yet the companies include data for several other types of meds anyway.

There are a few genes that have some data for antipsychotics, but again antidepressants in general are equal in efficacy, antipsychotics are not. So there isn't much data showing pharmacogenetic testing is going to give you a good compass for antipsychotics when utilized for that hope. Antidepressants on the other hand, there is data showing it can be helpful.

 

[Lindaroo]

I've done pharmacogenetic testing quite a few times as of this writing. I also used to work at the Lindner Center, a place where the testing was first offered (it's right outside of Cincinnati and Cincinnati is where they first tested the Genesight test).

Former Jolly Good Fellow, Thank you very much for sharing information regarding your experiences with the pharmacogenomic testing, and about the person who had the same history and resolution with treatment-resistant depression. It's been a difficult exercise to get further valid information and my family thanks you also. It is encouraging!

 

[whopper]

One more trick of the trade. I don't want to name the test, but it's one popularly advertised and it contains the MTFHR gene and runs about $100. It also tests for other genes that I've found helpful in looking for a bigger picture in treating a patient. That test is not advertised for health purposes but more entertainment purposes but it is CLIA approved so I have every reason to believe despite the maker's intent the gene test is accurate. I'm not talking about the ethnic heritage test but the ones that test for genes with known related health-impact.

So in situations where patients want to buy that test anyways, I tell patients why not? I've had patients give me the results of their testing and it does give me a bigger picture as to what's going on.

But aside from this, if I order an MTHFR test at a usual clinical lab and the insurance doesn't pay for it, it'll cost the patient about $400, and that's just for one freaking gene. Order the popular entertainment test they get tested for several genes many of which will tell me some important data.

 

[whopper]

One last thing about L-Methylfolate. All the studies I've seen focused on the patients getting 15 mg. I have seen several patients do much better on 30 mg daily but not all. In fact with many if they take too much they get bad side effects such as headaches, palpitations, nausea, and dizziness.

I recommend people either start 15 mg daily in a shoot-for-the-moon approach (the studies are all about 15 mg daily) or start 5 mg daily and go up another 5 mg daily per 3-7 days. E.g. 5 mg daily for 3 days then raise to 10 mg daily for 3 days then 15 mg daily for 3 days in a sort of turning on the hot water before a shower and feeling the water before jumping in approach.

The patients I've had who've taken 30 mg at first did so in a rather risky devil-may-care manner that I never recommended, but they came back to me reporting much better effects on depression. I only tell patients now to go above 15 mg daily if they can tolerate 15 mg daily fine and are in need of more improvement but to do so in a upping it by 5 mg daily every few days.

What I figure will go on is in the coming years the protocols for L-Methylfolate will be greatly improved. We're kind of standing at the 10% line of where the data is and clinicians often times in such arenas know more from clinical experience than the studies are yielding. This type of phenomenon happens actually quite a bit in medicine and more than we care to admit. E.g. ERs that kick out malingerers all the time without any suicides for years are quite comfortable in doing so but guess what? The protocols for doing so have never been well-established in medicine.

My own opinions on L-Methylfolate have greatly changed from seeing so many patients improve upon it. If you're willing to take (waste) your time you will be able to find prior posts from me saying I didn't like the idea of giving it out. Especially since back in the day the only main manufacturer stepping into the game was Deplin at about $300 a month (I know you can get it cheaper now, but back then you couldn't).

So as a recap-the data is solid L-Methylfolate does help as an antidepressant augmentation agent. While one's ability to physiologically produce it is linked to MTHFR mutations, and while MTHFR mutations have been correlated in several studies to depression we're not sure as doctors if we should be ordering MTHFR tests as a guide for L-Methylfolate recommendation and that test is expensive. While the dosages typically are 15 mg a day in the antidepressant augmentation studies I've seen some patients do much better on higher dosages but also seen patients even with the double-MTHFR mutation not be able to tolerate even small dosages of it although that is very rare.

In general from my experience people with the double-MTHFR mutation have more severe depression and earlier depression (e.g. starting even as a small child) and there is empirical published data backing this up.

While I would recommend L-Methylfolate to anyone with the double MTHFR mutation because their homocysteine levels are likely raised from that same mutation, I don't know how much more I'd go in that area with a single-mutation.

All of the above IMHO needs further refinement as more data comes in from future studies.

 

[Lindaroo]

One last thing about L-Methylfolate. All the studies I've seen focused on the patients getting 15 mg. I have seen several patients do much better on 30 mg daily but not all. In fact with many if they take too much they get bad side effects such as headaches, palpitations, nausea, and dizziness...

Thanks for posting this information and sharing your clinical experience. Much appreciated!