Our approach to mental health with depression and inflammation has been perverted by the influence of the pharmaceutical industry. According to a report released by the National Center for Health Statistics (NCHS), the rate of antidepressant use in this country among teens and adults (people ages 12 and older) increased by almost 400% between 198894 and 200508. In 2008, 11% of the population took them. In 2017 it was 17% of the population.

Selling selective serotonin reuptake inhibitors (SSRIs) is big business. The global sales of antidepressant medication is expected to be nearly $16 billion per year by 2023. Antidepressants are profitable, but maybe not as effective as those selling them would have you believe.

There are plenty of studies concerning the effectiveness of antidepressants, nearly 80% of which are funded by drug companies. In one study, only about 40-60 out of 100 people who took an antidepressant noticed an improvement in their symptoms within six to eight weeks.1

According to the authors of that study, There is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition. 2

Much of the information about the efficacy of antidepressants has been overstated. A report published in Psychotherapy and Psychosomatics states, Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy. These meta-analyses also document a second form of bias in which researchers fail to report the negative results for the pre-specified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure as though it was their primary measure of interest. The STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. Conclusions: The reviewed findings argue for a reappraisal of the current recommended standard of care of depression. 1

So, if boosting serotonin and other neurotransmitter levels doesnt work, what does?

Inflammation affects all organs, including the brain. In fact, it can be argued that because of its lipid content, the brain is more susceptible to inflammation than other tissue.

Recent studies are showing a link between inflammation and depression. One study looked at CRP levels in patients with major depressive disorder (MDD). Researchers found that high CRP levels made patients less responsive to treatment. High levels were also associated with cognitive impairment (which the antidepressant treatment did not affect).3

The authors of another study also found an association between inflammatory markers and depression. They stated, In conclusion, the level of IL-6 and hsCRP was increased in depressed outpatients but was not associated to specific depressive symptoms. In terms of cognitive function, we found that higher hsCRP levels were associated to lower psychomotor speed both at baseline and at follow-up. 4

Researchers evaluated baseline data from 2,861 participants from the Netherlands Study of Depression and Anxiety (NESDA).

The Inventory of Depressive Symptomatology and the Beck Anxiety Inventory were used to assess depressive symptoms and anxiety symptoms. For both scales somatic and cognitive symptoms scales were calculated. Baseline blood samples were collected to determine high sensitivity C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-5. The authors found a strong correlation between these inflammatory markers and depression and anxiety. They further stated that lifestyle may be the culprit. Another study found that inhibition of tumor necrosis factor improved sleep quality in depressed individuals. 6

The authors of yet another study state, Overall, inflammation causes disruptions in the blood brain barrier along with cellular and structural changes within the CNS. In vitro and in vivo animal models have shown that inflammation decreases neurogenesis in the hippocampus, induces glutamate release from microglia, and impairs LTP. Human MRI studies have shown that IFN and endotoxin treatments result in rapid changes in white matter structure, brain global connectivity, and functional activation, all of which are linked to depression and fatigue. 7

It should surprise no one that inflammation plays a role in depression. Higher rates of depression and fatigue have been shown across a broad range of conditions associated with activation of the immune system such as allergies, autoimmune diseases (type 1 diabetes, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis), and infections (sepsis).

Do not use curcumin and other natural anti-inflammatories as a treatment for depression. This is not much smarter than trying to bump up serotonin levels. Depression is a symptom, not its own disease.

Start with diet, which is probably the best way to start dealing with inflammation. Sugar, refined foods, chemical additives, too much starch and too much animal protein create inflammation. Seeds, nuts, brightly colored produce and essential fatty acids reduce inflammation.

George Goodheart exhorted us to fix what we find, and to not merely address symptoms. Addressing inflammation is a good start, but dont stop there. After all, you want to fix the patient who has the symptom and not merely treat the symptom. Nutrition is just like chiropractic in that it is all about balance.

If you go through the literature, you will find depression linked to problems with the thyroid, vitamin deficiency, the hypothalamic-pituitary-adrenal axis,8,9 inflammation,9,10,11 and even bowel ecology.10,12,13,14 The problem with looking at these issues is that it is impossible to find a single, patentable treatment so they are largely ignored.

If we look at depression as a symptom with many possible causes, we can come up with strategies to help these patients. Address inflammation, but also look at other things:

You get the idea depression does not have a single cause. Fixing the bodys infrastructure can work better than aggressively manipulating the bodys biochemistry with a drug.

There are many more references than are listed here. Also, other nutrients are useful. Low-dose lithium (see the Chiropractic Economics article about lithium as a trace mineral) and magnesium come to mind.

We are the profession that treats the patient and not the disease; we need to expand our focus. Going beyond manipulation and adding basic nutritional therapy can increase the number of patients we can effectively treat. Furthermore, we can be the answer to runaway medical costs, currently at $3 trillion a year and rising.

PAUL VARNAS, DC, DACBN, is a graduate of the National College of Chiropractic and has had a functional medicine practice for 34 years. He is the author of several books and has taught nutrition at the National University of Health Sciences. For a free PDF of Instantly Have a Functional Medicine Practice, email him at paulgvarnas@gmail.com, or for a patient handout on the anti-inflammatory diet.

Psychother Psychosom 2010;79:267279 Efficacy and Effectiveness of Antidepressants: Current Status of Research

British Medical Journal, (Br J Psychiatry. 2011 Jan;198(1):11-6, sup 1) Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis

Brain Behav Immun. 2012 Jan;26(1):90-5 Treatment response and cognitive impairment in major depression: association with C-reactive protein

Brain Behav Immun. 2014 Jan;35:70-6 The association between depressive symptoms, cognitive function, and inflammation in major depression

Psychoneuroendocrinology 2013 Sep; 38(9): 1573-85 Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA)

Brain Behav Immun. 2015 Jul;47:193-200 Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation

Front Immunol. 2019; 10: 1696. The Role of Inflammation in Depression and Fatigue

Prim Care Companion J Clin Psychiatry. 2001; 3(4): 151155. The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians

Eur Neuropsychopharmacol. 2017 Jun;27(6):554-559 Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation

Brain Behav Immun. 2018 Mar;69:1-8 Effects of obesity on depression: A role for inflammation and the gut microbiota

J Neuroimmunol. 2017 Dec 15;313:92-98 Inflammation-induced depression: Its pathophysiology and therapeutic implications

Curr Opin Psychiatry. 2017 Sep;30(5):369-377 Depressed gut? The microbiota-diet-inflammation trialogue in depression

Neurotherapeutics 2018 Jan;15(1):36-59. Anxiety, Depression, and the Microbiome: A Role for Gut Peptides

Int J Mol Sci 2022 Apr 19;23(9):4494 The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies

Psychosomatic Medicine October 2010 72:763-768 Dietary folate, riboflavin, vitamin B-6, and vitamin B-12 and depressive symptoms in early adolescence: the Ryukyus Child Health Study

Asia Pac J Clin Nutr. 2019;28(4):689-694. Vitamin D and depression: mechanisms, determination and application

British Journal of Psychiatry (Epublished ahead of print, July 12, 2012)

Biological Psychiatry (1 July 2007; Volume 62, Issue 1, Pages 17-24 Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder

Am J Prev Med. 2005 Jan;28(1):1-8 Exercise treatment for depression: efficacy and dose response

J Affect Disord. 2017 Feb;209:188-194 Exercise is an effective treatment for positive valence symptoms in major depression

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Depression and inflammation: how to treat the patient and not the ... - Chiropractic Economics