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Treatment-Resistant Depression: An Alternative Approach to Management

Treatment-Resistant Depression: An Alternative Approach to Management

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The subject is treatment-resistant depression (TRD) . . . specifically new management options for this common problem. Our speaker is B. Andrew Farah, MD, Chief of Psychiatry at the High Point Division at University of North Carolina Health Care system.

In this podcast, Dr Farah focuses on 3 topics:

• Shortcomings of current therapy that make TRD so common.

• New insights into the genetic underpinnings of TRD.

• A new treatment paradigm that puts non-drug therapies, such as oral B vitamin complex supplementation, as first-line treatment ahead of conventional antidepressants.

Speakers Panel: Accera, Avanir, Novartis, and Sunovion
Requested Speaker Panel membership with JayMac
Research Grants: Accera
Reviewer for JCP and Future Medicine

• Low monoamines are symptoms of depression
• Blocking the reuptake of NTs: symptomatic relief vs curative?
• The root cause of depression is the inability to synthesize adequate monoamines
Intracellularly, high HCY correlates with low monoamines and low B vitamins, particularly B6, 9 and 12, which act as cofactors for enzymes in the HCY cycle and for B9, BH4
• Metabolism of HCY reduces its toxic burden and results in monoamine and antioxidant production
• Individuals who undergo stress and develop depression have been shown to have polymorphisms for one or more B vitamins, that result in inadequate metabolism of B vitamins to the co-factor forms needed
• These polymorphisms likely represent the true genetic vulnerability behind depression and many other disorders and morbidities


Not a single peer reviewed article is referenced. Hold the champagne. I really wish it does work. But wishing does not make it true. The huge percentage of incomplete/zero responders to ADs is awful. But the lack of clinical science in this talk is disappointing.

Do the products taken orally cross the BBB as alphamethylfolic acid is supposed to? What are the statistics on response and remission to special-vitamin-product alone and with added AD? What are the rates of response and remission in patients of the same population who are given traditional ADs only? Show me the money.

Michael @

Indeed this presentation was anecdotal without a controlled trial etc. I have learned to keep an open mind and if a patient has failed conventional therapy and needs relief quickly i am willing to try anything as long as it doesnt put the patient at risk. Here is a reference to a link i think that fits right into this discussion. please read it and give me your thoughts! I have had a few patients fit into this subset of patients and do very well with therapy with L methylfolate (deplin). The pharmacology and science behind this tx is well presented in this article! It reminds me all too well of the one young man i saw (only too late) to find he had had wilsons disease all the years he was treated for psychiatric illness and died in his early thirties. If a zebra is in the room dont say it isnt so!!! http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1267
Dr Mark Holscher MD

mark @

Why not list some references on this page? Or would the facts get in the way of this discussion?

Darlene @

We already have this figured out. Visit www.neurosciencemyths.com to see how to normalize the neurotransmitter system.

yvonne @

Having been through years of very TRD, I spent months taking the "brain-available" B vitamins and folate he is touting. It was not cheap! This stuff was several hundred dollars a bottle. After draining my wallet on several bottles of this stuff, I realized it made no difference. Seems just another supplement product being promoted by doctors.

I have to wonder why the "chemical imbalance" theory was pushed by drug companies and doctors for so many years, even though the evidence of its failure was mounting. Probably was too profitable to pass up.

Now there are inexpensive options like ketamine that appear to hold great promise for TRD patients, but little interest in obtaining FDA approval for the treatment. All the businesses want to patent some ketamin-analog or business method for treatment so they can continue to gouge patients and their insurance for a low-cost procedure. Kind of like TMS?

Cuba @

try 5HTP, (herb) Q10, magnesium, keep hydrated. for digestion try Florstor®. all over the counter--not very expensive. no i dont sell them. just some suggestions. BE well! Cheers! neurocoach7

kent @

The research on Ketamine treatment for TRD is much more impressive.

Ellen @

The doctor is being funded by Accera, a maker of supplements to treat neurological disease. Check out their web site, and you will learn of a study using peanut butter to diagnose Alzheimer's- according to their information, the decreased ability to detect the smell of peanut butter from the LEFT nostril is associated with the disease. Right nostril odor detection didn't correlate. Interesting stuff.... BTW, massive doses of nicotinic acid to threat schizophrenia were briefly popular in the 1950's- not much new under the sun........

Jon @

Is the "chemical imbalance" theory dead? No knowledgeable psychiatrist believes it? Hardly. Here's B. Andrew Farah, MD, Chief of Psychiatry at the High Point Division at University of North Carolina Health Care system nattering on about "chemical imbalance" being responsible for "treatment-resistant depression" (via poor absorption of B vitamins!).

Will this junk science never die? Sure, people might feel better given vitamin supplements. Their diets have probably been poor all their lives. And never underestimate the placebo effect.

After being battered repeatedly with psychiatric drugs, it's probably a relief for patients to get merely interested attention and a vitamin for "depression."

Also, the adverse effects of prior drugs must be taking into account in "treatment-resistant" cases. Long-term post-discontinuation effects can be emotional anesthesia, sleeplessness, surges of anxiety, and post-SSRI sexual disorder, among others.

Patients may also have become hypersensitive to all neuroactive drugs, supplements, even foods. For such people, simply stopping attempts at drug treatment might allow their nervous systems to recover.

Truly, psychiatry is in a cave interpreting shadows on the wall. Lack of monoamines, indeed.

Alto @

please reference the MTHFR SNP mutation as the cause of inadequate brain active folic acid! there are 2 major SNP mutations for the MTHFR the C677T which is the most significant and if present will result in increase risk of thrombosis , cad and elevated homocysteine which in turn decrease's the amount of glutathione present in the brain which is needed for the production on monoamines. It also decreases the available SAMe to patients with this mutation. there is herterozygous and homozygous mutations. (homozygous patients have about 20-30 % of normal production and action of MTHFR) we methylate 1 billion times a second in our body! the other one is A1298C which again decreases the amount of glutathione available to the patient for production of momoamines.( but does not lead to increase thrombosis or cad we dont think!) taking very low doses of L methyl folate which crosses the blood brain barrier much better than folic acid can be a remarkable treatment adjunct not to mention lowering their elevated homocysteine which all will agree is a good thing! there is so much mis information and a lack of understanding about SNP mutations it is sad. the term epigenetic comes into play here. not everyone with these SNP's become symptomatic but if the patients is exposed to enough stress or trauma the symptoms of depression etc are more likely to occur!!
did you know the active form of vitamin D -calciferol is actually needed to produce glutathione as well ?? that is why patients with low or low normal vitamin D levels may be at risk for worse or TRD! Quest labs and most labs routinely do MTHFR tests now if ordered! do a search on pubmed. there are many more that you will find helpful to look into too. COMT MAOA SNP mutations etc.COMT is thought to be directly linked to Parkinsons disease of early onset now! the human genome experiment is starting to have real results in daily practice! imho/ thanks.
Dr Mark!

mark @

This seems to be a highly biased talk, as the speaker only mentioned one brand name product for B vitamin supplementation. The data he presented was annecdotal, not randomized/controlled. Are there data to support the speaker's assertions? What are the references?

Joseph @

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