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The Breakthrough Depression SolutionReview - The Breakthrough Depression Solution
A Personalized 9-Step Method for Beating the Physical Causes of Your Depression
by James Greenblatt
Sunrise River Press, 2011
Review by Roy Sugarman, Ph.D,
Jan 3rd 2012 (Volume 16, Issue 1)

The thing about depression is that it is largely a concept that has entered mainstream human discourse many years ago.  Although it has gone through its evolution as a concept, including reactive, endogenous, melancholic, adjustment, mixed with anxiety, psychotic versions, mood disorder versions, and so on, it remains rather poorly treatable.  This may come as news to the layman or patient, but despite the touting by the public organizations that band together to deal with the stigma of illness, and the best efforts of the drug company behemoths, the condition is largely a real challenge to get into remission.

As most researchers in this field know, multiple studies like the Star-D and other very expensive reviews, have shown disappointing responses to the best medication, and with few medications actually doing better than placebo, certainly not overwhelmingly so, and in many cases, not at all.

So despite the passage of time, a siloed approach to using medication as a surefire cure for depression in its very varied guises has proven limited, and the categorical summaries that constitute the working manuals for mood disorders, the DSM and ICD publications, have proven less than convincing.

Criticism of psychiatry has not just come from Scientology circles, but from within mainstream psychiatry itself.

So Greenblatt’s book is one of the publications which over the years has set out to step outside of the disease approach to depression, out of the silo of a medication for some entity approach, to one which would see a more integrated approach, a more medical approach rather than psychodynamic approach, to mood disorders.

This would mean more than say moving from a psych approach to a biopsychosocial approach, but to one with a more integrated view of the body itself for instance.

If one accepts that depression is the end state of a myriad of putative elements and causes, the approach to it must move beyond the simplistic germ theory or organ theory that has dominated the professions of mental health for some time.

Books such as this must then inevitably move into the field of personalized medicine, or what Greenblatt calls ‘biochemical individuality’ which would of course make the one pill fits all sizes approach severely flawed.  In this way, psychiatry is the medicine without measures, as he calls it, because there are not blood tests or other measures readily targeting depression directly rather than by subjective questionnaires for instance. Given the assertion that the physiology of the body and the chemistry of the brain are vitally interconnected, this together with genetics and epigenetics is the beginning point of Greenblatt’s integrated approach to a body-brain solution.

He will then outline his THE ZEEBrA approach, a beginning of integrated psychiatry, which then focusses on the individual as a unique personality, with an environment and metabolism to match, with connections between human body and mind to be understood, an approach that sees the restoration of healthy not just symptom reduction as its target, and a need to increase the body’s nutrient reserves to promote long term health.  To support this, his mnemonic then refers to Taking care of oneself, Hormones, Exclusion, Zinc, Essential fatty acids, Exercise and energy, B vitamins and others, referenced EEG, and Amino acids and proteins.

So we need to look after ourselves, reducing sugar, taking care of our digestion and sleep loading; hormones are making a comeback, as chapter 8 takes up, zinc, magnesium and other minerals are discussed in chapter 10, Essential fatty acids are looked at in chapter 11, exercise of course is proving vital and so is discussed in chapter 12, B vitamins and others are taken up in chapter 13, and the big one for him, referenced EEG is discussed further in chapter 14 as a way of directing treatment; amino acids finally are discussed in chapter 15.

So by now nothing clearly is a breakthrough solution or innovative, but what he is suggesting as the novel conclusion is to integrate an approach to treatment using the THE ZEEBrA approach as a scaffold. Everything in there is pretty much understood by the profession, but as the song goes, “it’s good advice that you just don’t take”.

Taking care of yourself turns out to include more than sugar, sleep etc, but also attention has to be paid to thyroid hormones and the way they are assessed, DHEA as a supplement, and the gonadal hormones as well.

Exclusion here refers in the next chapter to what one can exclude from the diet, namely a look at Celiac disease for instance, and various food allergies.

Zinc is a clear target for Greenblatt. So too little zinc, or too little or too much copper, are important in his reading of the literature. Magnesium is too, and then startlingly, he mentions Lithium in the form of lithium orotate at about 5-20mg. Chromium, Iodine, Iron, are also considered.  It would be quite hard to find evidence in the scientific literature to support the use of Lithium orotate as he describes it, but it is plausible, despite the threat of side effects as lithium is a toxic metal.

 The next chapter on essential fatty acids and cholesterol draws on the fact of the fatty content of each brain cell, and of course the myelin sheath.  EPA and DHA are the two he focusses on in respect of depression.  He asserts that low levels of EFA’s are linked to depression.  More essential is his well taken comment that pushing the levels of Omega 3’s too high can disrupt the optimal balance with Omega 6’s.  He recommends a ratio of 6:3 in the order of 4:1, whereas most would say 3:2 and of course Americans are probably at 15-20:1 and Australians somewhere around the 14:1 mark, depending on diet, especially if rich in processed food or inflammatory eicosanoids.

Again dear to my heart is his discussion of cholesterol and its valuable contribution to the human body in excess, by some margin, of any putative concerns around cardiac illness. Given recent demands from my own cardiac caregivers to push my cholesterol levels to virtually nothing, the reviews he presents that associate low levels of cholesterol with depression are certainly interesting. One would have to ask if the correlation is causal, or perhaps the result. However, cholesterol  is a precursor to so many interesting hormones in the body that one would have to consider these things.

A far easier case to make is for the role of exercise.  In the USA, presenting patients with first time depression will receive, in most cases, a series of medications, as opposed to the likely event in the UK for instance of being advised to exercise. John Ratey and other psychiatrists have certainly made the case in no uncertain terms in relation to a host of brain function, as he does here.  He links this to energy issues, referring to that as mood related inertia. Energizing the cellular environment includes the use of Vit B12, Carnitine, and strengthening that relationship, co-enzyme Q10.  Using Tofranil and a statin drug for instance, would deplete the body of Q10, depriving the cellular level of energy, as in depression. Ribose and whey discussions lead finally to a series of recipes, namely for a shake or two.

He continues with the Vitamins B and D, as well as an amino acid derivative SAMe, many being reduced by sugar intake and processed carbohydrates.

rEEG is a quantitative measurement of brain patterns against a large database to attempt to predict which medication might work best for that brainwave pattern.  Recent research, eg that by DeBattista et al 2011 in the Journal of Psychiatric Research, although limited, do indicate this may be a cheap and efficient first foray into personalized medicine, meaning the right medicine for the right person at the right time.

The biogenic amines involved in neurotransmission are food derived, and Greenblatt examines tryptophan and others in the context of low stomach acid and other suppressants of normal activity.

Measuring something is the key to managing, hence his opening words on psychiatry being a form of measure-less medicine, and so his chapters include one on what medical investigations might best be ordered to provide a baseline, given personalized medicine should start with a baseline.

Having returned psychiatry to medicine, he now feels relaxed enough to discuss things beyond biochemistry such as negative bias, placebo effect etc.  But his book is about beating the physical causes of depression, not the psychological, and so the input is brief.

So again, the breakthrough here is the integrated approach, and the elements of this have been around for a long time, and covered elsewhere in the literature. However, a siloed approach to just prescribing medication has not proven really impressive.  Any attempt by anyone to return psychiatry to medicine has to be valued, and add to the voices around the world calling for a more integrated solution to depression in all its guises.

There are many more elements known to science, eg see and recent articles in mainstream psychology magazines such as the APA Monitor have referred to the various elements of boosting body and brain as a single entity. Some studies have found limited value in, for instance, fish oil tablets, others on vitamin supplements, especially the anti-oxidants have found them to be of no value, and even downright dangerous. Nevertheless Greenblatt makes the case for doctors to approach the mood disorders as polymorphic, where one size fits all medication has pretty much failed.

No one is likely to argue with him, and breakthrough or not, this book provides valuable prodding for doctors, especially PCP’s in the USA, to do things not only differently, but with more medical elements and purpose. The HMO’s might not be too thrilled, as these tests and medications might stretch a few budgets and raise a few eyebrows, but patients would certainly feel more thoroughly attended to, and heard.  Adding a few psychosocial interventions would also go down well, to enhance the sense of self-efficacy of the patient and mobilize their own resource, a little thin in this book despite it being such an important part of recovery.

So overall Greenblatt has added in a useful way to the voices calling for psychiatry to return to medicine, and see physical causes for physical conditions such as depression.


© 2012 Roy Sugarman


Roy Sugarman PhD, Director Applied Neuroscience, Athletes Performance USA


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