L-Methylfolate: A Promising Therapy for Treatment-Resistant Depression?

Severe depression and L-methylfolate augmentation
Severe depression and L-methylfolate augmentation

L-Methylfolate: A Promising Therapy for Treatment-Resistant Depression?

I am excited to be adding L-methylfolate into my treatment plan. It’s back to nutrition and genetic mechanisms gone awry.

Folic acid in and of itself does not alleviate depression. Our brain must convert folic acid into L-methylfolate before it can manufacture enough serotonin, norepinephrine, and dopamine to alleviate depression. However, certain individuals lack the ability to convert folic acid to l-methylfolate, rendering folic acid supplements ineffective for this group of patients.

This processing deficiency is caused by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which is quite common among patients with depression. Up to 70% of patients with depression test positive for the polymorphism and therefore cannot convert folic acid into L-methylfolate.

For most psychiatrists, treating depression tends to be a frustrating search for the right therapy to help a patient reach remission. Nearly 2 out of 3 patients with depression do not achieve remission with selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) monotherapy—in clinical practice, this means that a psychiatrist treating 20 patients for depression could see 14 come back with little to no initial improvement of symptoms.(1) “It’s demoralizing,” said Rakesh Jain, MD, MPH, Director of Psychiatric Drug Research at the R/D Clinical Research Center in Lake Jackson, Texas. “Treatment-resistant depression is really the rule and not the exception.”

Treatment-resistant depression (TRD) is a term used to describe patients with major depressive disorder who do not reach remission after multiple antidepressant trials, including augmentation strategy, explained Jon W. Draud, MS, MD, Clinical Professor of Psychiatry at University of Tennessee College of Medicine in Memphis.

Individuals with ongoing depression are more likely to incur high medical costs (2), have employment problems (3), and experience suicidal ideation (4). “The ruinous effects of depression are amplified for people with treatment-resistant depression, so therefore there’s great urgency to treat these patients,” said Michael Thase, MD, Professor of Psychiatry at the University of Pennsylvania in Philadelphia.

Although the disease remains difficult to treat, researchers are continually seeking better solutions for patients with treatment-resistant depression. New studies, particularly a paper published by Papakostas et al in 2012 (5), have compelled psychiatrists to consider augmenting traditional antidepressants with the medical food L-methylfolate.

Unique Neurobiology

A medical food is a nutraceutical—essentially, a vitamin—rather than a pharmaceutical. However, unlike a vitamin, a prescription medical food such as L-methylfolate is regulated by the US Food and Drug Administration (FDA).

L-methylfolate (Deplin), is indicated for the distinct nutritional requirements of individuals who have suboptimal L-methylfolate levels in the CSF, plasma, and/or red blood cells and have major depressive disorder, with particular emphasis as adjunctive support for patients taking antidepressant medications. The medical food has attracted attention due to its benign side-effect profile and unique neurobiology. “It has a mechanism of action that is very different from what we are used to,” said Dr. Jain.

Traditional drugs such as SSRIs and SNRIs block reuptake of neurotransmitters, while L-methylfolate spurs the production of more neurotransmitters. “It primes the pump from within,” said Dr. Draud.

Dr. Draud added that clinicians might hesitate to use the compound because the mechanism of action is unfamiliar and because of a misconception that a prescription for folic acid is just as effective as L-methylfolate.

Literature suggests that depression is linked with folate deficiency (6) and that patients with insufficient folate are less likely to respond to treatment (7) and more likely to experience a relapse (8). Folate supplementation does help some patients, acknowledged Dr. Jain, but the full story is more complicated.

Folic acid in and of itself does not alleviate depression. Our brain must convert folic acid into L-methylfolate before it can manufacture enough serotonin, norepinephrine, and dopamine to alleviate depression. However, certain individuals lack the ability to convert folic acid to l-methylfolate, rendering folic acid supplements ineffective for this group of patients.

This processing deficiency is caused by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which is quite common among patients with depression. Up to 70% of patients with depression test positive for the polymorphism and therefore cannot convert folic acid into L-methylfolate.

“In a scenario like that,” said Dr. Jain, “it becomes important to not use folate but to use L-methylfolate directly. That way you don’t have to worry about the patient potentially having the genetic polymorphism.”

Source: http://www.psychcongress.com/article/l-methylfolate-promising-therapy-treatment-resistant-depression-11329


Severe Depression Treatment

Severe Depression Treatment – Part 1

Severe depression treatment series
Severe depression treatment series

You need an individualized treatment plan and a health care team to navigate through severe depression and to provide you with a safety net.

We all need someone to catch us when we fall.

Individualized Treatment Plan

Severe depression treatment plans can be tailored to your specific needs.  Scientists and scholars have yet to discover a cure, so while they are working behind the scenes on our behalf; work with your health care team to create an individualized treatment plan. It will be the key to optimizing your life and managing this chronic illness.

Create your team

To build a health care team, most individuals seek the best  and the brightest physicians, particularly for their stature in the mental health community regardless of location and availability–that’s not what’s in question here. The questions you need to ask are:

Severe depression treatment team
Severe depression treatment team
    1. Who does my Primary Care Physician (PCP) recommend?
    2. Is this practitioner accepting new patients?
    3. Do they accept your insurance?–If not, are they affordable?
    4. When is their first available appointment?–2 weeks, a month, several months?

Once you’ve answered those questions and have scheduled your first appointment; use a piece of paper or an index card to jot down these important questions to ask yourself during your visit:

    1. Do I feel comfortable and safe with this person?
    2. Is this person genuinely interested in providing the best care for me?
    3. Do they look at you when you’re talking or are they looking at a computer, watch or cell phone?
    4. How do they respond when you ask if they can work as part of a team? Is this a ‘Lone Ranger’ who will not collaborate as a team?

If you are satisfied with your assessment; there is one all important question. It’s the deal breaker.

Will this person and staff advocate on my behalf?


My hope is that my experiences can be of some benefit to you. Check back daily for new installments in my series on Severe Depression Treatment. Future series topics will include:

Professionals to add to your team

Your role and responsibilities as part of the team

Alternate medical therapies and interventions

Exciting research that is happening behind the scenes

If you have a question or topic you feel would be a great part of this series; please send me your ideas with this contact form:

Thank you – Ellen



There are no sides – just truth and compassion

crevice boulder

Recently, I was with a group of friends and acquaintances at a casual dinner party and out of the blue I hear a soft probing voice quip;  “So – Ellen, what are your thoughts on all this hype about mental illness being a disease now? Which side of the argument are you on?”

I don’t recognize the voice and I’m not even sure that we’ve even met. Is she being serious? It really caught me off guard.

As puzzlement started to skew my facial expressions, I decided to switch from puzzled to profound and said something like – “are we talking social perception or research and reality?” This bought me a little time to decide if I really wanted to teach her something or maybe banter around some of the enigmas enveloping mental illness.

I gestured for her to come a little closer to the group and simply said; “There’s some fascinating research going on that defies all that we thought about depression and mental illness. Where once our culture treated mental illness akin to leprosy, evil and weakness; a momentous leap in research is proving that mental illness is a treatable disease, a disparity between mind and body. Not unlike a chemical imbalance in any other organ. It’s rather exciting!”

Her eyes widened as her neck stiffened ever so slightly. A silent pause, I smiled with heartfelt conviction – she tilted her head just a little bit and as she smiled her dimples started sinking into her cheeks. It felt like I was just given a golden nugget – hard to explain with words – perhaps you can see me smiling as I type.

Short moments in time where my story can really make a difference. Being gracefully bold and addressing the stigma of severe depression and mental illness one conversation at a time, that one smile, that one blog that brings hope.

Why do I share? Lest I forget where I’ve been – lest I forget where I am now – lest I forget how far I’ve come.

Gracefully, Ellen


Triggers – PTSD

Triggers – PTSD

PTSD triggers warningSmells – Sights – Songs

Triggers hijack a moment and you are no longer, where you started. The smell of a person walking by that plunges you deep into a moment in time. Seeing an object that imprisons your speech and you cannot talk. The song playing on the radio that transports you back to terror.

Those with PTSD are intimately acquainted with their own triggers. Identifying our triggers can be painful and can short circuit a conversation with friends, a pivotal moment in an executive meeting or perhaps has you are sitting silently watching a movie. It is in those moments that I find myself digging feverishly into my mental toolbox as my body flushes to scarlet.  Should I stay or should I go?

My coping skills and mental tools vary in scope and effectiveness. Experience teaches me daily which skills will help me to safely navigate through each occurrence.

    • Dialectical Behavior Training (DBT) rescues me from a flash attack at work
    • Opposite thinking can salvage most of my conversations
    • ‘Mindfulness’ liberates my thoughts when seized with anxiousness
    • ‘Crucial Conversations’ training mediates those times when I’m tempted to be a door mat
    • ‘Crucial Confrontations’ skills equip me to diffuse anger and brings me back to a mutual purpose

However, recently I find I am not as quick to recover. The aftermath is becoming more and more difficult to clean up. Trigger events are happening with greater frequency or I am in a heightened sense of awareness. There are times when I can anticipate and prepare and then those times when it smacks me flat in the face. This is when I struggle the most.

Addressing my triggers and the carnage they wreak on my life, has become my primary focus for the summer. So far, I’ve identified a few triggers:

    1. Basements
    2. Handkerchiefs
    3. Watching movies/shows that depict rape or incest
    4. Walking into a dark room
    5. Father’s day

I will be working on the basement issue and simply avoid the rest for the time being; one thing at a time, baby steps.

I declare that my God will envelop me with his presence and mighty warrior angels will be surrounding me as I walk into my basement today.

Chipping away at the stronghold PTSD has on my life one chip at a time.


How My PTSD Affects My Depression

PonP040513_NCAPM_74b9a755da366c702c59c379808e5fe8As I compile my thoughts on how PTSD (Post Traumatic Stress Disorder) has affected my depression, I realize that the relationship between my PTSD and depression has morphed throughout the years into an intricately choreographed dance. A dance of medications, counseling, crashes and insight. Whether my PTSD and depression were birthed by family composition, trauma or genetics, they have been engrained into my psyche and life.

Image0 (1)Brain chemistry hijacked by Cortisol

In early childhood, while my brain was engraving neuropathways, the whole process of growth was hijacked by the hormone Cortisol. Cortisol was released by my adrenal glands in response to the trauma I was experiencing from continued sexual abuse by my father. Scientific studies have proven an overabundance of cortisol fries neurotransmitters, hijacks neuropathways and disorders all the intricate connections within a child’s brain. A deeply engrained depressive state was becoming attached to my PTSD. Trauma after trauma continued throughout my childhood, evolving into what I now know as PTSD with concomitant Major Depressive Disorder.

PTSD weaves toxic tapestry

toxic tapestryWhile I was cloaking my torment and suffering from the eyes of teachers and friends, the complex face of PTSD was growing and weaving a toxic tapestry within me. PTSD rarely exists without its companion depression and despite all my efforts, threads of PTSD and depression became visible from time to time. The tapestry of mental illness has become heavy; fraught with divorces, adult physical/sexual abuse and a skewed sense of self. The depth and weight became more than I could handle myself and I sought the help of psychologists, psychiatrists, intense therapy and hospitalization.

PTSD related flashbacks short circuiting sleep

good short circuitMy most recent bout with flashbacks, nightmares, and severe sleep deprivation brought me to a point where I needed intense inpatient therapy and a change of medications. The focus of my therapy was to identify how I could disable the nightmarish flashbacks. First we identified the cycle, flashbacks deprive me of sleep; sleep deprivation nurtures depression; depression feeds on trauma and PTSD. Then we discussed my options.

New medication ransoms sleep from PTSD

Once we agreed to target the flashbacks, my care team suggested adding a high blood pressure medication ‘Prazosin’ that has been shown to eliminate the nightmares and flashbacks of veterans returning with PTSD. After adding the new med, I have experienced sleep as wonderfully restorative and at times whimsical. I am gaining the strength I need to address my depression and tackle my daytime flashbacks.
Determining how my PTSD and depression interacted became a pivot point in my life. The springboard to continue thriving and enjoying my life.

Sources: Childhood Abuse



Sleep, Sabotage and PTSD

Winsome Library ArchiveEvening envelopes me as I enter into sleep and the adventure that has been mine since taking Prazosin.

I enter softly into a winsome, colorful library that I perceive to be all my dreams that were smothered by my PTSD. Some sections are sorted by color, another by whimsy and many more yet unexplored. Perhaps there’s a dream I’m dancing and playing with my children and grandsons waiting to be opened.

As I have written in my previous posts “Fear -Minus the Fiction” and the subsequent post “Winsome Dreams Welcome Here – Prazosin”; a new prescription has effectively negated the nightmarish flash backs that have haunted every evening of my life since 9 years old.

It is becoming eminently clear to me that PTSD nightmares were sabotaging my library of dreams that were there, but always smothered by the nightmares.

How can I describe how it has felt throwing out the nightmares by way of Prazosin? An analogy comes to mind; like a dark lit alley, damp and odorous, no contrasts just darkness and trash. Suddenly a metal door opens to the alley and this huge bag of trash is simply tossed out into the tunnel. The door closes and faint sounds of laughter emanate from the inner most part of the adjoining door.

As I confidently leave the trash in the alley, I find myself entering my library as sleep walks me to the doorway of my newly discovered archive of dreams.

I’ve always loved libraries.

Well, it’s 10pm in my corner of the world and here I am cozy with a cool breeze wafting in from the window.

My encouragement to my readers: Victories oft-times come after a long period of waiting – praying with all my heart and soul that you will soon be wandering in your dreams yet opened.

I advocate talking with your physician and care team about the blood pressure medicine ‘Prazosin’. Please do not self medicate and seek wise counsel on your medications.



Winsome Library Archive

Navigating through severe depression and PTSD

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