Here is some interesting information from Robert J. Hedaya, author of the book “The Antidepressant Survival Guide: The Clinically Proven Program to Enhance the Benefits and Beat the Side Effects of Your Medication”
Posted by By Robert J. Hedaya, M.D., D.F.A.P.A. on January 28, 2009 – 12:00pm
The Anatomy of Depression: Part I
GOAL: The person with depression is in a complex homeostatic state, albeit a disturbed, negative, painful one. The task of the clinician is to develop an understanding of the homeostatic processes (social, biological, etc) involved, and the nodal points that require intervention. The clinician must then intervene at as many of these points as possible, at the same time, to re-establish a new more functional equilibrium.
THE PARADIGM: Neurotransmitters are built from a number of essential nutrients. The process, not too different from making a ‘big mac with special sauce’, requires that certain ingredients (e.g., tryptophan, tyrosine, B vitamins, folic acid, B12, magnesium, etc.) be available in adequate supply. High demand (i.e., stress, certain medications such as stimulants and prilosec) requires a greater supply of the essential ingredients. If any of these is in short supply production and maintenance of a steady state is impaired. In addition, the breakdown and or recirculating of the neurotransmitters requires other nutrient dependent processes (e.g.folic acid, methionine). The task of the clinician is to assess the adequacy of diet, nutritional value of the food sources, digestion, and absorption of the key ingredients used to make the neurotransmitters.
BEN’S STORY: In June of 1985, Benjamin sat in the corner seat of my waiting room, feeling distraught and humiliated. Recently released after three weeks on “the psych ward” at McLean Hospital, this rejection-sensitive young man was still highly anxious, experiencing panic, hopelessness and suicidal ideation. His pain was poorly disguised by a thin veneer of quick humor. Using a combination of individual and group therapies, and phenelzine (an MAO inhibitor), gradually, over 5 years, he came to live a full life, and his visits to me were reduced to a biannual event, when I would catch up with his life, and enjoy some of his excellent sense of humor. In 1989, I switched Benjamin over to fluoxetine (Prozac) which lacked the risk of a hypertensive crisis. Benjamin did quite well, and eventually, he married and had three children. His wife, stressed by the maternal role which her own mother had abdicated, developed fibromyalgia. Benjamin’s parent’s health and finances deteriorated. As the breadwinner of his own family, and only child to his parents, his stress level rose significantly. In August of 1999, Benjamin came for an early visit. Fourteen years after his first panic and depression, he was now having a recurrence of the panic attacks. He was terrified that he would end up back in the hospital. He was convinced that he needed to change his medication to Zoloft. “I think it’s ‘Prozac Poop out’, he said.
THE PARADIGM: In general, when one is depressed regardless of the causes (i.e. metabolic, nutritional, social) distortions in one’s thinking become part and parcel of the depression. Selective attention to these distorted thoughts (usually catastrophic thinking, all or nothing, etc-for a full description of this read Aaron Beck’s Cognitive Therapy of Depression or “Feeling Good” by David Burns) is the norm for depressed patients. One aspect of the treatment of the depressed person is identifying these thoughts, the nature of the distortion, testing the logic behind the ‘automatic assumption’.
BEN’S STORY: I asked Benjamin what basis he had for thinking this, and explored his logic. I asked him if there were any other ways of looking at the situation. Finally I reassured him that hospitalization would not happen, and explained the reasons why (e.g., panic could easily be treated with a short acting benzodiazepine while we were searching for the cause, we could increase the frequency of contact as needed rather than use the hospital, he had a relationship with a psychiatrist he trusted, and who cared about him, whereas that was not the case 15 years earlier), knowing that it was important to deal directly with this negative thought and preoccupation.
THE PARADIGM: Untended, this “catastrophic fear” was causing anticipatory anxiety (activating his dorsal raphe nucleus), priming his limbic system for panic (locus coeruleus), and feeding-forward via the amygdala and locus coeruleus into full fledged panic, and the ‘hypothalamic-pituitary-adrenal gland (HPA) axis-activation-positive-feedback’ loop. It would become a self-fulfilling prophecy.
Having addressed this thought, I explained to Benjamin that ‘Prozac poop-out’, (the commonly held idea that the antidepressants often stop working after a while) was not a concept that makes sense. If a person with unipolar depression is fully responding to an antidepressant in an essentially stable manner for several months or more, and then relapses, it is incumbent on the practitioner to search for other factors that are now over-riding the medication (assuming adherence to the medication), such as psychosocial changes and stressors, as well as any aspect of metabolism.
At this point I decided that in order to approach the situation with ‘fresh eyes’, I would evaluate Benjamin as if he were a new patient. I would do my best to leave no stone unturned, no assumption of mine unchallenged.
Tomorrow, I will detail the surprising domino-like events that nearly brought Ben to his knees.
By Robert J. Hedaya, M.D., D.F.A.P.A. on January 29, 2009 – 9:12am
BEN’S STORY (Continued): I decided to start with the psychosocial stressors – (being a parent, having an ill wife and parents) and delve into the nature of how these stressors changed his life, and how he adapted to them. Apparently, Benjamin had to take a detour from his own career in order to manage his parents finances, control his mothers spending, and deal with his fathers business. When the day was done, he would come home to his ill wife and do most of the house work. Having little support, Benjamin began to cope by stress-eating. He gained weight, began to experience indigestion, and excessive belching. His family doctor, concerned about gastro-esophageal reflux, placed him on Prilosec. Benjamin noticed a significant improvement in his indigestion and remained on the drug for three years before his present panic attacks and depression recurred. However, now the recurrence of panic shook his confidence and he felt that he was losing control of his life and his mind, once again.
THE PARADIGM: Knowing that Prilosec could inhibit B12 absorption, (it inhibits the very cells that produce intrinsic factor, which is necessary for B12 absorption), I eventually convinced Benjamin that he should be worked up for a B12 deficiency secondary to the Prilosec. Despite his distress, he was quite resistant to this idea. The detection of B12 deficiency is difficult. One can look for a macrocytic anemia (large red blood cells also called high MCV), low serum B12 levels, or high levels of methylmalonic acid. However, a number of studies indicate that these tests are often falsely normal when tested against the gold standard Schillings test (no longer available).
Martin Seligman’s learned helplessness model of depression demonstrates that despite their pain, some depressed individuals actively resist help. The neurophysiology of mood disorders suggests that a certain part of the prefrontal cortex (the ventromedial prefrontal cortex) whose function is to accurately predict or anticipate rewarding experiences and pleasure, or painful consequences, has reduced activity.
Because Benjamin complained of indigestion, bloating, constipation, and gassiness, I also evaluated him for bacterial overgrowth of the small intestine which can impair nutrient absorption. An IgG panel for delayed food sensitivities, a comprehensive digestive stool analysis, and an adrenal saliva test rounded out the work up.
BEN’S STORY: When he finally agreed to the workup (one year later), he indeed turned out to have a B12 deficiency. His methylmalonic acid and CBC were within normal limits, although his MCV was trending to the upper limit of normal, and his red blood cell count was trending toward anemia. These trends indicated that a macrocytic anemia was developing, but that the effects of the B12 deficiency manifested themselves first in Benjamin’s weakest system-his nervous system. The only test that was abnormal was a functional intracellular assay of B12 function. With the introduction of B12 injections Benjamin’s panic and depression cleared completely.
The next two tasks were to help Benjamin address the stressors in his life, and his stress-eating response. Based on the test results a number of dietary changes, a program to rebalnce his gastrointestinal milieu, nutritional support, as well as meditation and a regular exercise program were instituted. Benjamin lost weight, discontinued the Prilosec, and felt more in control of his life. He has been without panic or depression since then (8+ year follow up).
I saw Ben last week, and he told me “I am at a high point in my life.” Many of his career aspirations were coming to fruition, and family stresses were becoming more manageable as his attitude was maturing. Is this just a nice, sugar coated story with a happy ending, or are there lessons to be learned from Ben’s difficult passage? You decide.
(Adapted with modification from: Depression: Advancing the Treatment Paradigm, Robert J. Hedaya, MD, FAPA, 2008. IFM.ORG)