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Making Sense of Antidepressants & Health

When wading through the river of health advice, where you can find people saying one thing is good and other people saying the exact opposite is good, it’s helpful to have a couple strategies for logically vetting information. Some lines of logic are better than others: “Ah, not a bear in sight! The bear patrol must be working like a charm!” “That’s specious reasoning, Dad.

By your logic, I could claim that this rock keeps tigers away.” “Oh, how does it work?” “It’s just a stupid rock!” “Uh huh.” “But I don’t see any tigers around here, do you?” “Lisa, I want to buy your rock!” I want to share with you four things to consider when analyzing health related information.

The History The Context The Mechanisms, and The Short term vs. the Long Term As we go through each of these four, we’ll look at examples of how this can apply to evaluating diets or medications, but throughout the video, I’ll look in particular at antidepressants.

I should say at this point that this of course isn’t intended to be medical advice, and if you happen to be on an antidepressant, whatever you do, don’t abruptly stop taking it without consulting a professional. Let’s start with history.

For diet, this usually means looking at the diet from an evolutionary perspective. For example, if I were looking at the fruitarian diet, I would be critical of the fact that it’s very unlikely that we were eating primarily fruit in prehistoric times considering our guts shrank as our brain got bigger.

But, even if we were eating fruit, the fruit we would have gotten back then wouldn’t have been much at all like the modern day fruit that through domestication and cultivation has come to be much bigger and much sweeter.

As Daniel Lieberman points out in his book “The Story of the Human Body,” “almost all the fruits our ancestors [did eat] were about as sweet as carrots.” That means a prehistoric fruitarian diet would be more like a modern day vegetable diet.

Moving on, when looking at medicines or prescription drugs, we’d want to know the history - what was the logic that led to the development and application of that drug? Let’s compare the history of insulin to the history of antidepressants.

The history behind insulin, very briefly, goes like this: A disease called type 1 diabetes was discovered that was causing children to waste a way and die within months. German scientists suspected the pancreas was at fault for diabetes in 1889, and Eugene Opie in 1901 very accurately suspected that a lack of an internal secretion specifically from the islets of Langerhans in the pancreas was the major problem.

Scientists made several attempts at turning the pancreas into a medicine, feeding patients raw pancreas, giving them ground up extracts of the pancreas - with not so great results. Finally, in January 1922, after many discouraging failed experiments, David Banting and Charles Best with the vital help of James B. Collip, successfully treated a boy’s diabetes with a pancreatic extract.

This marked the discovery of insulin and was a historical moment for medicine. So, in the case of insulin, the cause of the disease was first well theorized, and then a medicine was created based on the assumed pathology of the disease.

Okay, so what about antidepressants? The order of events is very different. In 1955, Bernard Brodie and Arvid Carlsson found that an herbal drug called reserpine seemed to make animals “lethargic,” “apathetic,” and “depressed.” This mood depressing drug also reduced brain levels of norepinephrine, dopamine and serotonin.

These three are all technically monoamines but norepinephrine and dopamine are classified as catecholamines. Then, it was found that the drugs iproniazid and imipramine could prevent the lethargy and apathy if given before the depressing drug reserpine - iproniazid and imipramine seemed to have a anti-depressant effect.

These two so called “antidepressants” blocked the usual depletion of the catecholamines: dopamine and norepinephrine and blocked the depletion of the monoamine serotonin. You may be familiar with the famous chemical imbalance theory of depression and other mental disorders.

Joseph Schildkraut deserves some credit for this, in 1965 he said that “some, if not all depressions are associated with an absolute or relative deficiency of catecholamines, particularly norepinephrine.” After that, researchers quickly turned much of their attention to serotonin, guessing a deficiency in serotonin to be a root cause of depression.

So in this case, researchers first understood how a drug worked, then assumed the cause of depression based on the way that drug works.

What’s the problem with this? The American Psychiatric Association’s own 1999 textbook explains that assuming depression is caused by low serotonin because a drug that seems to prevent depression raises serotonin “is similar to concluding that because aspirin causes gastrointestinal bleeding, headaches are caused by too much blood loss and the therapeutic action of aspirin in headaches involves blood loss.”

So in 1999 the APA is making fun of the how the chemical balance idea came to be. The next point is about context, which is especially important to consider. For example, in the context of a low carbohydrate diet, plenty of good quality butter could be perfectly healthy and not make you gain weight, but if you’re consuming lots of butter in the context of a high carbohydrate diet, the insulin effect of the carbohydrate is going to have you store more of the butter you eat as body fat.

And, eating a lot of carbs by themselves is very different from eating a lot of carbs when they’re wrapped in fiber- in the form of vegetables.

There are many other contexts to look at, an obvious one is genes - certain populations can be more susceptible to certain diseases, and certain gene polymorphisms can affect your levels of certain vitamins like folate, Vitamin B6 and B12, beta-carotene and vitamin D.

Grains, dairy, sugar and soy are what she’s particularly wary of, but things as seemingly healthy or at least harmless as almonds, rice, white cabbage, bananas, citrus, onions and zucchini have all given her major issues when she’s tried to reintroduce them into her diet. For the past six months she’s been on a diet that is just meat, salt and water - this was the last step in diet improvement for her.

She says on her blog that on the all meat diet, she just feels better and better, her brain is the fastest it’s ever been and she’s happy and energized all day. And now, she takes no medications at all.

Going back to antidepressants again, we’d want to know the context in which you introduce this medication. A genetic test for example would be helpful, but before you introduce a drug that increases serotonin signalling, we would at least want to verify that the person actually has low serotonin levels.

Especially because antidepressants are known to have a very high risk for complications including the potentially life threatening serotonin syndrome and a black box warning for “suicidal thoughts and behaviors.” But… As researchers at McMaster University explain, “It is currently impossible to measure exactly how the [living] brain is releasing and using serotonin…” However there is a kind of workaround for this.

After serotonin is pumped into the synapse, it is either taken up into the pre-synaptic neuron for later use or it is metabolized by an enzyme into 5-hydroxyindole acetic acid (5-HIAA). Researchers can comb the cerebrospinal fluid for this metabolite for an indirect measurement of serotonin.

So, we should expect that people with depression would have low levels of 5-HIAA meaning they have low serotonin. But, how well does this pan out? In 1971, investigators at McGill University failed to find a “statistically significant” difference between the 5-HIAA levels of depressed patients and normal controls and there was no correlation whatsoever between depression severity and levels of 5-HIAA.

Then in 1974, two researchers at the University of Pennsylvania found that a serotonin depleting drug didn’t reliably induce depression at all. Then, in 1975, investigators at the Karolinska Institute in Stockholm found that thirty percent of the depressed patients they tested indeed suffered from low levels of the serotonin metabolite 5-HIAA.

But, they also found that 25 percent of the “normal” group also had low cerebrospinal levels of these metabolites. Finally in 1984, NIMH investigators wanted to see whether those depressed patients with low serotonin would be the best responders to an antidepressant. Unfortunately for the chemical imbalance theory, lead investigator James Maas wrote, “contrary to expectations, no relationships between cerebrospinal 5-HIAA and response to [the antidepressant] amitriptyline were found.”

Simply put, researchers assumed that antidepressants were working their magic in a certain context based on what the antidepressant does, not based on proper evidence for that context. The next thing you’ll want to investigate is the mechanisms behind whatever food, diet or medicine is in question.

This can be a difficult step depending on your understanding of biochemistry and pharmacology, but that doesn’t mean the concepts are out of your reach. For example, let’s say you hear that margarine is bad for heart health whereas good quality butter is actually good for heart health.

For some, this may sound dubious as it’s the opposite of what we’ve been told in the past - You can even find the mayo clinic website saying “Margarine usually tops butter when it comes to heart health.” as recent as last month. But then you learn that the vitamin K2 in butter promotes the decalcification of soft tissues like the heart because decalcification is a vitamin K2 dependent process.

And, the hydrogenated vegetable oil in margarine inhibits these vitamin K2 processes making it easier for soft tissues, like the heart, to calcify. “I can’t believe it’s not butter!” We now even have mechanisms for how the cholesterol-lowering so called “heart-saving” statin drugs actually worsen calcification of the heart.

Statins block a step in this decalcification process. Now that you have a mechanism in mind, you can investigate further. If you look up “statin-induced arterial calcification,” you’ll find papers showing that yes, high dose or long term statin therapy advances arterial calcification.

Going back to the antidepressants, this one of the problems - the mechanism for how they work is not known. For example with the common selective serotonin reuptake inhibitor, SSRI-type antidepressants - we of course know they inhibit reuptake of serotonin, but it’s not known why that would have a therapeutic effect.

Have a isten to Psychiatrist Daniel Carlat’s comment on this: “But on the other hand, what we don’t is we don’t know how the medications actually work in the brain… when patients ask me about these medications, I’ll often say something like, well, the way Zoloft works is it increases the levels of serotonin in your brain… and presumably the reason you’re depressed or anxious is that you have some sort of deficiency.

… I say that because patients … certainly don’t want to hear that a psychiatrist essentially has no idea how these medications work.” So with antidepressants, we don’t actually know why they would work, and there’s doubt about whether they actually do work. “Today, British researchers said several popular antidepressants are essentially no better than a placebo.”

However, some people have experienced antidepressants as being truly helpful and life saving, making the topic of their efficacy complex and out of the scope of this video. The last point is the Long Term vs. Short Term.

This is a very tricky to consider when it comes to nutrition for many reasons, one being that the body is constantly adapting and responding to what you put into it. For example, many people have had weight loss success on caloric restriction diets, but some will find later on that it’s difficult to maintain the lost weight thanks to an adaptation called “metabolic adaptation” This is where the body drastically reduces its resting calorie burn and makes you hungrier from hormonal adaptations in response to the calorie cutting.

This leads us to maybe the most concerning point about anti-depressants. Most of the more recent data on depression today turns out to be data on medicated depression. It’s widely thought that depression is a chronic disease, and patients are often informed that they’ll have to take antidepressants for life to keep their chemical imbalance corrected - sort of like a diabetic who needs to take insulin long term.

Then, it’s very common for people to have a depressive relapse when going off the drugs, which is thought to be evidence for the necessity of drugs. But what happens in people who just don’t take medication? In Robert Whitaker’s book “Anatomy of an Epidemic,” he explains that before the age of antidepressants, people’s depression would usually resolve by itself eventually.

A 1931 long term study of 2,700 depressed patients reported that more than half of those admitted for depression only had one depressive episode and no relapse. A Swedish physician, Gunnar Lundquist, followed 216 depressed patients for eighteen years and found that 49% never experienced a second depressive episode, and 76% became socially healthy and could resume their usual work.

Bulgarian psychiatrist Nikola Schipkowensky said that tricyclic antidepressants were inducing the disease to “change to a more chronic course.” Then, in, 1995, an NIMH study looked at people diagnosed with major depression who received antidepressant treatment and those who did not. At the end of 6 years, the people who received the medication were more than 3 times as likely to have stopped functioning in their usual societal roles.

Finally, in 2006, Robert Posternak led a study that looked at people who had a depressive episode who, after recovering from the first bout of depression with medication went on to relapse but did not use medication thereafter.

It was found that 23% of these unmedicated people recovered in one month, 67% of them recovered in six months and 85% recovered within a year. So while antidepressants might be speeding up the recovery for some depressed people in the short term, thanks to the medication, the depression becomes a long term disease.

History, Context, Mechanisms and the Short term vs. the Long term - four points for investigation that by themselves won’t necessarily allow you to say “case closed,” but it will help you more efficiently process incoming health or diet information and make better conclusions.