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Depression: Why Anti-Depressants Aren’t The Solution


Anti-depressants are easily one of the most prescribed drug in the United States, where in 2013 they were the 3rd most prescribed drug recorded.  There is certainly no shortage of Prozac.  The unfortunate truth for many people is that, if you can’t get to the underlying cause of depression, psychotropic drugs have little use or value.  Psychiatrists use the DSM-IV criteria for major depressive disorder, where at least 5 of 9 symptoms present while accounting for severity for at least two weeks is evidence for a depressive state.

These include: feelings of sadness/emptiness, decreased interest in pleasure, a 5% change in weight or appetite, change in sleep patterns, psychomotor agitation, loss of energy/fatigue, inappropriate feelings of guilt/worthlessness, an inability to focus and thoughts of suicide.7

This article is focusing on chronic depression rather than your occasional blues.  In non-chronic depression, it is often an easier remedy that involves exercising, changing your relationships and lifestyle, direction in life and possibly with the help of some nutrients that are lacking.

The Issues With Anti-depressants

Tryptophan is the building block amino acid for serotonin, a neurotransmitter that regulates your mood, behavior and sense of happiness.  In chronic, serious depression models, this along with dopamine is believed to be deficient in a depressed patient, known as the monoamine hypothesis.  The common and expected treatment is to increase serotonin levels with SSRIs, MAOs and similar drugs that modulate brain activity.

The belief is that in depression, there is either a lack of serotonin being sent from the ascending neuron or that it is being reabsorbed too quickly.  SSRIs work by preventing the reabsorption.  This allows serotonin to hang out longer in the synaptic cleft, the space between two neurons, so they can exert their effect on the neighboring neuron.  This may temporary be effective, but in reality, they have a short lifespan and the evidence fails to show their efficacy.  Also, these drugs go through homotypic modulation, which means the receptors lose their response to serotonin and become resistant to it when there is a flood of serotonin in the synaptic cleft. The patient then is given a different drug when it not longer works and continues to cycle through various drugs over time, leaving the patient back to where they started.  And the frustration continues.

The reason for depression isn’t because we have a Prozac deficiency. 

These drugs do nothing to address the underlying cause, which is hardly a serotonin deficiency.  In fact, meta-analysis studies (which is the strongest evidence in the evidence based hierarchy) reveals that anti-depressants are insignificant in their effects, are ineffective with sustained use and exhibit a 10% advantage over a placebo.5  Furthermore, studies demonstrate that the “benefits” of anti-depressants is correlated with a reduced response to the placebo rather than a positive response to the drug.6   In addition to their lack of efficacy, there are a host of side effects and nutrient depletions in the body (like nearly every drug) like vitamin B6, B9, B12, vitamin D, essential fatty acids (omega-3) and sodium.

Because BH4 and iron are cofactors that are needed to make 5-HTP, which is then used to make serotonin, it is possible in short term depressive mood states that there may be a deficiency in these elements.  A B6 deficiency may be present as well.  However, generally supplementation of 5-HTP is not a solution either.

There is an urgent need to view depression through a much broader lens.

Diagnostics for Potential Causes

Depression is not exactly a mood disorder.  Dr. Datis Kharrazian describes it as a decreased frequency of firing in areas of the brain.  Ultimately, one must identify the reason why the brain is losing its communication network with neurons.  Hence, one needs to rule out other potential contributors the misfiring.  A thorough evaluation of the patient and diagnostic testing is a must.

Depression is rarely ever an isolated issue, and more often than not, there is a comorbidity of depression and some other present ailment.  Some common patterns are depression and anxiety; depression and low blood sugar and depression and insomnia.  These other seemingly “unrelated” issues are likely indeed a correlated.  Without addressing the other issues, depression hardly disappears for good.  Therefore, there is a good chance that there is at least one or more other abnormality occurring in the body that manifests as depression.

Healing the entire body is the focus when treating depression.

This is not an exhaustive list, but some areas to consider when investigating depression are blood circulation issues, chemicals, gut health; IBS, gut bacteria imbalance, food sensitivity/allergies,thyroid issues, methylation issues (i.e. MTHFR), hormonal imbalances (i.e. high and/or low cortisol), autoimmune diseases, high blood sugar, insulin resistance, nutrient deficiencies and any debilitating condition where inflammation is a big player, including physical injuries.  Head injuries must also be considered and post-traumatic encephalopathy is a cause for chronic inflammation and thus, depression.

Depression is also a clue that can foreshadow a potential major neurodegenerative disease.

The cytokine theory is the purported model for depression and that it is an inflammatory pathology. When there is an immune response, monocytes and other immune cells secrete cytokines.  Biomarkers of inflammation like hs-CRP and cytokines like IL-1, IL-6, IL-10 and TNF-a measured in serum are helpful in detecting if there is an inflammatory condition exacerbating and/or causing depression.  Evidence shows that there is a linear connection with these elevated markers and mood status.1-2  Abnormal cytokine levels and a dysfunctional immune system are found in patients with major depression and suicidal thoughts, alluding to the idea that these biomarkers can be indicative of depressive episodes.3Evidence also expounds the notion that when one can mitigate inflammation, clinical symptoms are much improved.4

To draw a brief biochemical description, when there is inflammation in the body, cytokines like IFN-y change the way tryptophan is metabolized.  The byproducts of tryptophan catabolism quinolinate and kynurenate are then produced from immune cells (macrophages) and astrocytes (brain neurons) and regulate brain activity.  Quinolinate is an NMDA agonist, meaning it interacts with NMDA receptors in glutamatergic neurons in the brain.  Essentially, this means that quinolinate overstimulates the NMDA receptor and cause hyperexcitability, similar to what glutamate (MSG) can do.  This damages neurons overtime and induces lack of firing in the brain.  When there is a cascade of inflammatory chemicals being spewed out by immune cells, the glial cells in the brain perpetuate inflammation that never quite subsides and shuts down the frontal cortex of the brain in chronic depression.

Interestingly enough, anti-depressants have been shown in studies to exert anti-inflammatory properties, which would explain the ephemeral, short-lived benefits of the drugs.  Cortisol, a natural hormone produced by the adrenal glands, functions to control inflammation.  People with depression commonly have low levels.  Conversely, too much cortisol from chronic stress can cause depression because it’s been shown to damage the rain, notably causing atrophy to the hippocampus.  Anti-depressant drugs have also been indicated to increase cortisol sensitivity suggesting that they improve inflammatory conditions; thereby, falsely attributing their success to the monoamine hypothesis.

Recommended Diagnostic Testing:  Vitamin and minerals (i.e. vit. D, folate, b12), hormones, antibodies, genetic assay (MTHFR), adrenals: salivary cortisol, fasting glucose and insulim, HbA1c, Homocysteine, hs-CRP, thyroid panel.

Dietary and Lifestyle Modification

In any depression situations, controlling and reducing inflammation through diet and lifestyle (managing stress) should be well assumed.  Depending on the severity of imbalances, like blood sugar and insulin, adapting Paleo style diet is quite useful.  A diet that revolves around high amounts of healthy fats from animal protein, fish, nuts and seeds and vegetables is a brain supportive diet.  Remember that your brain neurons are roughly 75% fat and your cell membranes are 50% fat – half of which is saturated fat.  Everyone needs a healthy amount of omega-3 fatty acids as well.  A modest amount of fibrous, nutrient dense carbohydrates has a place for controlling blood sugar levels and providing prebiotics for gut bacteria.  Drastically reducing sugar intake, along with removal of gluten and GMOs would be advisable as well.  It would also be prudent to incorporate an abundance of anti-inflammatory spices and herbs.

Turmeric is a well-studied and powerful herb that has even been demonstrated to be as effective as Prozac.4 Dampening systemic inflammation is the goal, and especially in the brain due to the destructive corollaries of glial cell activation.  Turmeric, resveratrol, lutein, quercetin and other bioflavonoids help suppress this activity that no medication can do.

Inclusion of probiotics and correcting vitamin and mineral deficiencies is a critical aspect that needs consideration.  Gut health is one major area often overlooked that needs immediate evaluation because inflammatory compounds produced from the microbiota or from food reactions can pass through the blood brain barrier and induce brain inflammation.

The common denominator though when manipulating diet for depression is resolving the inflammation and removing pro-inflammatory fats (i.e. trans fats, severely limiting omega-6 vegetable oils and arachidonic acid animal protein) and simple/processed carbohydrates.

The specifics of supplements and other interventions is based upon an individual basis, but these general recommendations can go a long way.


SSRIs and MAOs may provide transient relief, but with prolonged use, the body adapts, loses its sensitivity to the drug and rejects it from overstimulation, much like in insulin resistance.  Ultimately, the patient gets nowhere and can relapse and the internal regulation of serotonin in the body says impaired.  Anti-depression medications don’t provide a solution, but ignore other root causes.  Looking for the holes in one’s health is a prerequisite to resolving depression.  Functional medicine offers this more comprehensive investigation that demands urgency in every patient.


1)  http://www.ncbi.nlm.nih.gov/pubmed/19150053
2)  http://archpsyc.jamanetwork.com/article.aspx?articleid=1485898
3)  http://www.ncbi.nlm.nih.gov/pubmed/23645137
4)  http://www.ncbi.nlm.nih.gov/pubmed/23832433
5)  http://www.ncbi.nlm.nih.gov/pubmed/20051569
6)  http://www.ncbi.nlm.nih.gov/pubmed/18303940
7)  http://web.archive.org/web/20070630225823/http:/dsmivtr.org/index.cfm

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