Why We Need To Re-Think How We Treat Depression
By: Dr. Nicole Roberts, Naturopathic Doctor
I was re-reading some work by Dr. Kelly Brogan, MD the other day about the history of depression treatment and its shaping by the psychiatric and pharmaceutical industry. Her article was a reminder of (or perhaps an introduction to) the manipulation of science that has been undertaken by industries built to turn profit by selling psychotropic drugs directly to the public and to the medical doctors that are overwhelmed by a system of high patient volume.
I then read an article by Siddhartha Mukherjee, an assistant professor of medical oncology at Columbia and author of The Emperor of All Maladies: A Biography of Cancer. He has a fascinating and unparalleled talent for painting historical pictures about the development of disease and the human blood, sweat and tears that have gone into medical research over the years. Mukherjee is an intellectual at heart; he likes to lay out everything we know with a critical mind, and pose questions that illustrate the more we know, the more we know we don’t know.
And “not knowing” is the medical communities’ deepest insecurity.
Whether it is the responsibility or the ego associated with being a medical practitioner, it is difficult as a patient to contend with what a doctor thinks they know to be the absolute truth. Whether in conventional medicine or natural / alternative medicine realms, you will find a whole lot of “This is the answer.”, “I know best.”, “I have found the cure.” and so on and so forth.
Admitting we don’t know everything, which is all we really can do when it comes to the complexities of the human body, is the key to helping patients heal and move forward. Here we will discuss how we can best do this for those suffering from depression.
From my medical education and the continued research I do in the field of anxiety and depression, which seems to align with the findings reported by Mukherjee and those exposed by Dr. Brogan, this is what I know about to be true about treating depression (though I say this with an open mind).
1.) We need to stop falling into the trap of believing that depression is solely about neurotransmitter (serotonin) deficiency.
2.) We cannot rely on antidepressant drugs as our first line therapy for mood disorders, particularly for mild to moderate depression.
3.) We cannot ignore the plasticity of the brain and its ability to re-wire itself while being fed doses of psychotropic medications that (could) have depressogenic capabilities.
4.) We cannot let our health care be determined by industries that have deep pockets and are primarily focused on filling their own coffers. Capitalism and vitalism cannot thrive together unmanaged.
Let’s explore these a little deeper.
Serotonin is well known as our “feel good” or “happy hormone”, despite that term being simplistic and reductionistic when describing all that this specific neurotransmitter does.
Science stumbled across the idea that serotonin was at the root of mood when tuberculosis patients treated with iproniazid became radiantly euphoric and patients treated with Raudixin for blood pressure became depressed and suicidal. Each of these drugs had severely polarizing effects on mood and mental health, and science later connected these findings through drug-related increases and decreases in serotonin in the late 1960s.
Thus was born the “chemical imbalance” theory of depression, though flawed because a drug-induced depressed state could not be considered the same as naturally occurring depression. In the years that followed, many studies were undertaken to understand if “naturally occurring” clinical depression was caused by lower levels of serotonin; some studies found it was, others found no reliable connection. As Mukherjee summarizes in his compilation of The Science and History of Treating Depression, a study run on healthy male volunteers where low serotonin was induced, showed no noticeable change in mood. But all this just didn’t jive with the explosion of Prozac, an SSRI, on the North American market, and how good some people were feeling on it. What was depression and did how could we reliably treat it?
Mukherjee’s conclusion after reviewing decades of studies, each fraught with their own biases and design flaws, was simple.
“These slippery, seemingly contradictory studies converge on a surprisingly consistent picture. First, patients with severe depression tend to respond most meaningfully to antidepressants, while patients with moderate or mild depression do not. Second, in a majority of those who do respond, serotonin very likely plays an important role, because depleting serotonin in depressed patients often causes relapses. And third, the brain-soup theory — with the depressed brain simply lacking serotonin — was far too naïve.” - Siddhartha Mukherjee
Mukherjee then went on to examine studies that linked neuronal growth in the hippocampus to reduced symptoms of depression. Electrical stimulation of the nerves in the subcallosal cingulate of the hippocampus “lightened” the dark abyss of depression in patients. Interestingly enough, these nerves are particularly sensitive to serotonin. Science was now left with a conundrum; was depression a result of low serotonin, or a result of neuronal death in a some small recess of the brain? Or was it a combination of the two and what else was possibly involved?
Those were, and still are, questions with few definitive answers.
What is most fascinating about the depression, is that all depressions do not arise from one traceable root source. The depression associated with neurological decline (dementias, Parkinson’s) are qualitatively different from postpartum depression or major depressive disorder that carries a genetic link.
For example, depressive symptoms associated with neurodegenerative processes can present themselves as early as 2 decades before the motor symptoms of Parkinson’s begin. (1) Dopaminergic neurons loss in the midbrain is the most well-known neurologic change in Parkinson’s, but noradrenergic and serotonergic neurons are lost all over the brain. (1)
“A prevailing model for development of depression proposes that degeneration of mesocortical and mesolimbic dopaminergic neurons causes orbitofrontal dysfunction, which disrupts serotonergic neurons in the dorsal raphe and leads to dysfunction of depression-related orbitofrontal-basal ganglia-thalamic circuits.” (2)
A lot of words there, but essentially, the pathology of depression begins with dopaminergic neuron loss and spreads from there; a chain reaction of neurodegeneration leading to rewiring and further deficiencies, one symptom of which is depression.
In postpartum depression, the pathophysiology is still not well understood; it is very likely that different women and different pregnancies will elicit different causes of depression. In pregnancy, the endocrine system changes massively; ovulation is postponed, corticosteroid and other feedback mechanisms re-circuit themselves, the maternal immune and metabolic system must account for the growth of another organism with unique DNA and social stresses of pregnancy and motherhood arise. We know the thyroid undergoes changes in its regulation during pregnancy, and that postpartum hypothyroidism is a possible outcome. Poor thyroid function can induce a state of depression. Now turn 180 degrees, and a 2008 study proposes that some postpartum depression arises from changes to the regulation of the GABA(A) receptor.(4) Despite our lack of clarity about postpartum depression causes, we can see the topographical breeding ground for postpartum depression looks much different than that of Parkinson’s Disease.
Long story short, causes of depression and anxiety are multifaceted and spread across multiple body systems. Everyone who experiences despair, low motivation and hopelessness, key symptoms in the diagnosis of depression, has a different cocktail of reasons for feeling that way. While it is simple to label someone experiencing despair as clinically depressed and then write them a prescription for “antidepressants”, it is not an effective strategy at the individual level.
As Dr. Brogan keenly points out, this wake up call is not just for medical doctors, but for natural medical practitioners like naturopathic doctors who have fallen back on using amino acid and botanical therapies designed to increase serotonin; a natural version of antidepressant medications if you will. While it may, and I emphasize may, act as a stop-gap in the interim, this treatment strategy is still missing the mark when it comes to holistic, root cause treatment of depression and anxiety if not coupled with other therapies rooted in lifestyle medicine.
Did you know these other diagnoses can be at the root of clinical depression?
- Hypothyroidism. Changes to thyroid function are common after pregnancy, periods of chronic stress or infections. Yet the thyroid may never be tested before antidepressant medications are prescribed.
- Relative or actual discrepancies in estrogen or progesterone production.
- Digestive health and gut flora health. There have been cases of long standing clinical depression resolving after a course of antibacterial / anti fungal regimes that changed the gut microbiome for the better. SIBO, leaky gut and IBS are all possible root causes of poor mental health that require a gut healing protocol, not a prescription for antidepressants.
- Vitamin and mineral deficiencies. B-vitamins, omega-3 fatty acids, vitamin D and other brain supporting nutrient deficiencies have been well documented as a contributors to mental illness. Evaluating digestive absorption, autoimmune causes of nutritional deficiencies, methylation status, and diet are essential first steps in approaching mood disorders.
- Food allergies or other inflammatory conditions. Inflammation that may originate in the gut, and then trigger the immune system, can change brain composition and affect brain chemistry. Fun fact: A large percentage of certain neurotransmitters are made in the gut.
- Stress, Diabetes, Metabolic Syndrome. Cortisol and insulin are directly related to fluctuations in blood sugar control, which can create symptoms of depression like lethargy, irritability, anxiety and more. Some pharmaceutical agents that improve insulin sensitivity were found to lessen symptoms in depressed individuals. Insulin sensitization is a key target with lifestyle medicine.
As we can see from the above outlined causes, and considering the genetic link of certain depressions and other mental health diagnoses, if we for a second separate the body and the mind, which naturopaths are loathe to do, we can see instances of depression where the body first influences the brain and other instances where the brain first influences the body. If we apply the principle, the more we know the more we know we don’t know, we can assume that there are many complex interactions going on within the nervous system, the brain, the metabolism, the gut, the endocrine and immune systems and more, that we have not accounted for in the initial “chemical imbalance” theory. We also know that patients presenting with clinical depression have unique stories, unique diets, unique stressors, unique coping mechanisms unique genetics and unique biochemistries.
So then with all these unknowns, what is a doc to do?
First and foremost, we need to clarify our roles as physicians. Medicine must return to its roots of healing, rather than simply labelling and medicating. A diagnosis is not useful unless we can use it as a tool to move forward.
As naturopathic doctors, our first mandate is To Do No Harm. If the therapy in question may cause harm, we need to weigh the risk to the potential benefit it may offer a patient, and this must be presented to the patient so that they may make an informed decision as to how they want to proceed. In cases of severe depression, Ensure No Harm Is Done by the patient unto themselves or others, may come before Do No Harm with therapeutic treatments. Informed consent, if the patient is able to give it, must include a discussion about:
- Side Effects: Pharmaceutical interventions are highly susceptible to “Paradoxical Reactions” in which the symptom they were intended to treat is actually worsened, and possibly magnified, by the medication. Worsening depression and magnification of suicidal thoughts and behaviours, particularly in those under the age of 25 is a serious black box warning on antidepressants.
- The cost of the medications over the time you will be prescribed them, or at least until your next follow up. Further to that, an estimate of how long you will be on the medications and what result is expected in that time frame.
- The potential for needing to change medications or be put on multiple medications and the cost of that.
- The potential interactions with other medications the patient may be taking; particularly pain killing medications, anti-inflammatory medications, blood pressure, heart or diabetes medications, etc
- Alternative or concomitant treatments to medication: lifestyle changes, counselling, laboratory work, finding a sense of community, working on the processing of grief, etc
As a naturopathic doctor, our training mandates every patient has a thorough understanding of risk, benefit, cost and alternative options to every treatment prescribed, most of which are non-pharmaceutical. We give the power back to our patients through education. This discussion needs to happen around psychotropic and antidepressant medications in every clinic room where a prescription is written.
Secondly, mainstream clinical medicine needs to recognize the impact antidepressants have on brain structure and chemistry. Not only are we potentially “band-aiding” the symptoms with these medications, but we are changing the structure of function of the brain in serious and lasting ways.
A study run by a team of researchers looked at the brain with functional MRI scans pre and post a single SSRI dose. Within hours of taking the SSRI, overall connectivity within the brain decreased, while increased connectivity was found in only 2 areas; the cerebellum and the thalamus.(3) The researchers were shocked at the short amount of time it took for brain function to change post SSRI dosing and hypothesized that this may be the functional beginning of neural circuitry changes that occur with long term SSRI use. Other studies have described the ability of SSRIs to change the volume of certain areas in the brain of depressed patients, while shrinking these same areas or increasing volume of new areas in non-depressed patients.
Whether we see these changes on MRIs or in autopsy reports, we know that administering a substance to the body repeatedly changes its function and can create addictions with severe withdrawal symptoms. Drug, food, caffeine, sugar and other addictions are associated with brain changes that have long been discussed and documented. What is sad and somewhat backwards in the use of antidepressant medications is the high likelihood for worsening depression as a patient attempts to come off their antidepressants, even at a slow, tapered dose. We put patients between a rock and a hard place with this medical model and doctors often keep patients on their antidepressants to avoid what they call “a relapse” despite a more accurate term being “withdrawal”.
With the technological and laboratory advances we have made, the scientific community is now in the process of evaluating epigenetic and DNA methylation at the promoters of specific genes, to develop and target antidepressant therapy for the individual. The science I have read on this paints this as a brand new, wonderful solution for helping depressed patients who have tough cases. While I appreciate science’s effort towards finding personalized solutions for the biochemistry of an individual, I can’t help but wince at the short sighted trap I fear this research will fall into, especially when coupled with the pharmaceutical industry’s knack for marketing and capitalizing on vulnerable conditions. Targeted gene therapy is a brilliant advancement for inherited genetic mutations. However, using pharmaceuticals to push epigenetic changes could lead to disaster. Choosing a single gene to manipulate, without knowledge of the upstream and downstream effects of changing this gene's function, is perilous. We are only scratching the surface of understanding what our genes are capable of, and the more pinpointed we become in our therapies and the more we reduce disease down to one change, one methylation site, one biological pathway, the more blind we become, and the more chaos we can create. Lifestyle medicine (diet, sleep, nutrition, stress management, exercise, etc) has been influencing epigenetic changes for centuries; in a holistic, comprehensive way. Lifestyle medicine does not target a single gene with disregard for the rest of the organism, it targets the organism as a whole, hence the term holistic. It is my wish that as the human race continues its quest for knowledge about the human body, that we stay humble and leave our corrupt need for money and adoration at the door. Easier said than done, I know.
And so I conclude with my third point, and I almost hate to say it because my training biases me, but with all of the question marks floating around about the exact biological underpinnings of depression in the individual, it makes sense that treating with diet, lifestyle, sleep optimization, stress reduction and other wholistic methods, all of which affect the body’s biology in all kinds of wonderful (known and unknown) ways, is a good baseline therapy. These interventions, or what used to be called living well, have been talking to our brains, our cells and our genetic material for thousands of years; we know they shape healthy organisms that live healthy lives. Not only must we provide the basic fundamentals for human health, but we must take a hard look at the obstacles to mental wellness and work on removing those. Smartphones, alarm clocks, nations built around economic wellness over mental wellness, daily doses of media that insist we are not good enough so our self esteem takes a hit and we buy a pair of shoes on the way home to feel better……all these influences need to be called out and dosed out in moderation.
We need to learn how to thrive in the modern world.
Antidepressant medications do have a place in medical care. Research has shown us the benefits of these medications in major depressive disorder and other psychiatric conditions. Sometimes, a pill is the most efficient way to get us from point A to point B. All I’m saying is that we cannot stagnate at point B anymore. We must embrace the whole picture, acknowledging, that for everything we think we know about the human body, another question will arise and another adaptation will quietly change the human biochemistry, shifting us in a new direction.
And so at the end of this article, that became far longer than it was ever meant to be, there are no conclusions, but we’re simply left with one more voice advocating for a return to simple healthy living as a basis for treating depression and other mood disorders, before, or in some cases along with, a prescription.
Conflict of Interest Statement: Dr. Nicole Roberts, ND is a Naturopathic Doctor with a private practice in Toronto, ON. It is not within her scope of practice to write prescriptions for antidepressant or other psychotropic medications.
1. Depression and Parkinson’s Disease: Current Knowledge. Marsh L. Curr Neurol Neurosci Rep. 2013; 13(12):409
2. Depression in Parkinson's disease: a biochemical and organic viewpoint. Mayberg HS, Solomon DH. Adv Neurol. 1995; 65():49-60.
3. Serotonergic Modulation of Intrinsic Functional Connectivity. Schaefer A et al. Current Biology. 2014; 24(19): 2314-2318.
4. Understanding the pathophysiology of postpartum depression: Implications for the development of novel treatments. Nemeroff CB. Neuron. 2008; 59(2): 185-6.