Obesity, an Inconvient Truth
It may be boring, but the threat is to our metabolic health.
Mental health. It’s really important. What is it, specifically, one might ask? Important. That’s a good answer. I’ve been hearing this for years. Every time there’s an article in the New York Times, which is like multiple times a day at this point, many people send it to me. Yes. I already saw that thing in the Times.
Everybody1 agrees: the mental health crisis is crisis-tastic. It is super crisis-y. It’s here. No one’s denying the hereness of the crisis. But most people probably couldn’t pick it out of a lineup. I can. It looks horrifying. I’ll show you:
The Mental Health Crisis is the ManBearPig of our day. And just as Al Gore…
… was unjustly pilloried …
… for saying boring and reasonable things about climate change, I will take a completely uncalled-for swing at the eminently reasonable former government official speaking up about the badness that is mental health care in America:
Tom Insel, M.D., whom I don’t know personally…
… is heralded as a learned sage. Because he says things like:
A brief response by our narrator, O. Scott Muir, M.D., to the above points:
This isn’t what happens.
We don’t.2
It definitely isn’t.
It turns out that things Dr. Insel says, as the former head of the National Institute of Mental Health, and things anti-psychiatry Scientologists say, are eerily similar after we remove the editorializing (from the church of Scientology):
Psychiatric methods involving the butchering of human beings and their sanity are condemned by the Church. Scientologists are trying to create a world without war, insanity and criminality. Psychiatry is seeking to create a world where man is reduced to a robotized or drugged vegetable-like state, so that he can be controlled.
I’ll restate this so it’s less… ecclesiastical:
Psychiatric methods involving [treatment that doesn’t do a robust job of modifying morbidity and mortality] are condemned by the church. Scientologists are trying to create a world without war, insanity and criminality3. Psychiatry is [utilizing interventions with significant risks and less potent benefits] where [[hu]man[s] often face symptoms and side effects] that [include sedation], and [limited interventions for cognitive impairment exist] especially [in the context of the management of acute agitation].
Ok, so maybe that required more significant editing to make it fit for public consumption than I had initially hoped.
I’m being a little bit cheeky here, but they’re not that far off on the facts, just incorrect on the attributions. Let’s look at how much more likely people are to die with psychiatric illness at old age (when most of the dying happens):
I’m gonna make the argument that a lot of this has to do with obesity, and further that the mixture of psychiatric illness and psychiatric medications, specifically antipsychotics, lead to these problems.
While I’m pretty sure the issues Scientology is concerned with are not around the rates of obesity4, particularly severe obesity, these are serious problems that are driving disability and death.
Their word butchering is a bit much, but if we use my word substitution and talk about morbidity and subsequent mortality, it’s pretty hard to argue they are fundamentally off-base:
The above data is from Christoph Correll5 M.D. and his remarkable SATIETY6 data set. On the vertical axis is number of pounds gained, and the horizontal axis lays out different medications in the “second generation” antipsychotic class. We also have a matched control group, not exposed to these medicines.
Now here’s the unsettling part: these are weight gain numbers in children who had never been exposed to antipsychotic medication before. They are given the drug, and we’re seeing between 10 and 20 pounds of weight gain just in the initial time frame of a research study, compared to kids who aren’t taking these meds. This is a real world sample—it was kids who were observed after being prescribed the medicine by their doctors. That was the whole study.7
Above is data from adult studies. This is a meta-analysis with a vertical axis measured in kilograms, co-authored by doctors Correll8, Peter Manu, John Kane, et. al. We can see that virtually all of the dopamine-blocking drugs (antipsychotics) have an important risk of weight gain.
When we put this weight gain and obesity data together with the earlier deaths seen in patients with schizophrenia, a picture emerges. Patients with psychotic illnesses are often prescribed antipsychotic medications. They are also frequently used to “augment"9 not-that-effective SSRI treatment. The bullet point version looks like this:
Psychiatric patients are dying 20 years earlier than the general population.
Many medications prescribed have a significant risk of weight gain, particularly in severe and persistent mental illness.
This weight gain is present even in kids treated with antipsychotic medication for the very first time.
Over time, psychiatric populations have higher and higher rates of obesity.
It’s not all because of the medications, but it’s a serious health problem.
The causes are complex:
You know what else was mechanistically complex? Climate change. But it was also really freaking obvious:
And similarly, there were a lot of attempts by industry to make it seem like radical change in paradigm was not clinically or politically feasible.
The first-line treatment of major depressive disorder with SSRIs leaves many people with significant symptoms.10 Which has been addressed by pharma by repurposing second-generation anti-psychotic medications—some of our only treatments for psychotic illness—as mildly effective11 augmentation strategies for incompletely effective oral antidepressant treatment:
So there is a difference in the above outcomes data. But it’s not a big one. It’s a difference that is statistically significant, but on the order of 2 to 4 points on the MADRS. It’s the kind of result that would be in keeping with a shrug and response of “Yeah, I guess,” if you asked your waiter if it was worth ordering dessert at the restaurant. Similarly, underwhelming data exist for medication like quetiapine:
Again, there’s a change, but it’s not a big change.
You could make it look like a bigger change if you use misleading statistics like “improved clinical benefit“ and just use a percentage of people who noticed something, anything, and only in the positive direction. But again, a percentage of people who notice something = underwhelming. And as we can see, side effects driving the switches between medications, searching for something, anything, is common. This ends up represented in pharmaceutical advertising as follows:
See, the person is being lifted out of the crippling hole of depression with just one hand. You know, because she hasn’t gained a tremendous amount of weight as a side effect of Abilify yet!
My Personal Journey
To make it perfectly clear, I have a very personal interest in this particular issue. I have bipolar disorder, and I have been treated with anti-psychotic medications over the course of many, many years. They were helpful for a long time. My doctor no longer prescribes them for me, because it turns out other things are even more helpful. But the metabolic consequences over time are obvious. And when placed in reverse chronological order, you’re going to see why the mental health crisis and obesity is the climate change of healthcare, using this one very personal (but easy to obtain consent for) story:
I reached a peak of 247 pounds in October of 2021. Here’s a photo from around the holidays:
I am wearing my hilarious psychedelic medicine Christmas sweater, but the amount of abdominal obesity isn’t funny. It was devastating, metabolically, and also for my general health.12 This was a process that took many, many years to get as bad as it did.
The above photograph was taken in 2019.
I found this picture of my torso dating back to the age of 23, so we can understand the arc:
So, it’s not that I gained some weight on antipsychotics. It’s not that most people don’t gain some weight over time. It’s that these medications are capable of creating sustained and devastating metabolic consequences over many, many years, which personally took me from 127 pounds to 247 pounds. This was with attempts on the part of my doctor to mitigate the risk with the use of topiramate, metformin, and other first-line approaches to reducing the risk of antipsychotic-induced weight gain. I was a success story for weight gain.
The Devil and Daniel Johnston
This kind of weight gain kills people early by decades. We don’t typically include these deaths in the numbers related to the mental health crisis—for some reason, only suicide counts there, and maybe overdose? We only count cardiovascular mortality and stroke as other causes of death, and not predictable consequences of a mental health crisis… of mismanagement of the metabolic health of people with psychiatric conditions. I present the brilliant and beloved indie rock musician, now tragically dead by heart attack, too young—Daniel Johnston:
And after years of life-prolonging treatment with an antipsychotic medicine, clozapine:
He eventually died of a heart attack 10 years later in 2019.
Daniel Johnston had schizoaffective disorder, reportedly, and wrote some of the most compelling music that has ever been written, according to the likes of Kurt Cobain, Beck, and the Flaming Lips. He was also a gifted visual artist. But the above photographs illustrate a man getting older and sicker and dying before he should have. And he was famous and brilliant.
People worked hard to keep Daniel alive because they cared so much about the work and the man. But even that wasn’t enough. The devil wasn’t voices in his head, it was the metabolic syndrome that led to the failure of his heart. It’s a crisis, but it moves slowly and destroys one’s quality of life before it takes it away, more often than not.
Daniel Johnson survived a goddamn plane crash. His psychotic symptoms led him to crash a plane into the ground. That isn’t what killed him. A heart attack did. Daniel died at the age of 58.
We Need Better Treatments—Both More Effective and Safer
The good news is that we have these very treatments NOW. I will now place the above graph (about the clinical efficacy of the antipsychotic augmentation strategies) next to a graph demonstrating the effectiveness of an antidepressant treatment with absolutely no risk of weight gain whatsoever :
We saw that graph before. Now let’s compare it to the outcome of the most recent FDA clearance of a depression treatment using fMRI-guided Transcranial Magnetic Stimulation, Magnus Medical’s SAINT treatment:
For context, anything below a 10 on the Hamilton rating scale for depression is no longer depressed. You’ll notice that the second graph isn’t about a change in score. It’s actually absolute score on the vertical axis. Between 25 and 30 is badly depressed. There’s no statistical funny business, it’s raw data.
And now, a quick review of the side effect profile of antipsychotic medication used for augmentation of ineffective anti-depressants:
And:
Sorry, that’s accidentally a picture of my abdominal obesity last year and weight tracking from my personal apple health app. Here is the graph I was looking for:
Those are adverse reactions from Seroquel. Do you see diabetes mellitus there? Pancreatitis? Ketoacidosis? Those are all actually side effects of the same weight gain problem we’ve been discussing. It’s making people very sick. It made me very sick.
Luckily, modern medicine has ready answers that are actually pretty good. Glucagon-like-peptide-1 inhibitors (GLP-1) like Semeglutide are allowing life changing metabolic consequences to be reversed and or prevented in rapid order, with between 15% and 20% weight loss in randomized control studies. This includes the necessity of diet and exercise, but it makes them work dramatically better.
We Invest in the Wrong Things
The mental health crisis has led to an explosion not just in concern about mental health care, but in the funding of start-ups designed to disrupt the existing paradigm. Unfortunately, despite all that funding, it’s been about disrupting the way treatment is delivered, not the treatments that are delivered by in large:
Those companies have the following range of business models:
That is a lot of companies.
The mental health companies that are being funded are addressing problems that are easily addressable and understandable by venture capitalists and disruptive (aka mid 20s) founders. They are not necessarily the kinds of solutions aimed at solving the problem of people dying 20 years earlier. That's a harder problem to understand.13
It Is Probably Better Just to Make a Wellness App That Can Go Direct-To-Consumer and Scale Pretty Quickly?
There isn’t a telehealth-only solution that allows you to perform transcranial magnetic stimulation or put a tape measure on someone’s belly to measure abdominal circumstance. You need to be in person. There are telehealth solutions, many of them, that allow one to prescribe a range of oral medications for any given problem.
But if the only solutions you have, if the only solutions you allow yourself, are oral medications, you’re going to miss out on the most effective and safe treatments that exist.
The real problem, we all know it, is the ManBearPig/climate change of psychiatry, metabolic devastation:
And the serious metabolic consequences of letting ManBearPig run wild are as serious as the consequences of climate change. It’s a different world you get to live in when the oceans are 15 feet higher. It’s a different world you get to live in when you’re 100 pounds heavier than you were a short time ago. It’s not a better one. It doesn’t have to be that way. It’s limited by our imagination, by our political will, by our investments, and by our focus.
I was lucky enough to get to an obesity medicine doctor who knew how to help my weight gain problem with modern treatment:
To quote Dr. Gore—sorry—Insel:
We have to remain humble about our understanding of the brain, because even our most powerful tools remain pretty blunt instruments for decoding the brain. In fact, we still do not know how to decipher the basic language of how the brain works.
Our old medications are life-saving for many. This includes me. I’d likely have been dead in my 20s if it wasn’t for olanzapine14 specifically, one of the worst offenders when it comes to metabolic torture.
And we absolutely, positively, need to do better when it comes to safety, tolerability, and efficacy. And without a holistic (otherwise known as biologically plausible) approach to the health of humans, it doesn’t work. This means care of health, including airdrops of nutritious food and exercise plans to people, come hell or high water:
A more important Insel Quote is from the infographic:
There is a mental health crisis. It’s the fact that we don’t treat mental health as health, and in fact are willing to ignore the devastating impact on general health in the service of inadequate treatment of psychiatric illness.
When all you have is a hammer, it’s time to start innovating better hand tools, not accessible nails to allow for more efficiency in crucifixion.
If you're looking for care that doesn't put you at risk for obesity, it's worth considering the clinical services my team provides:
** Get care at Radial **
—O. Scott Muir, M.D.
Actually, it’s only 90%. That’s basically everybody, right?
Some of us are working really hard, and I mean very specifically @carlenemac and her team at @osmind, to change this.
These are grandiose laudable goals. It’s not entirely clear to me if stewards of the church of Scientology like David Miscavige are succeeding at the elimination of all insanity, war, and the like. But there seems to some debate:
In fact, antipsychotic induced weight gain is entirely absent from charges levied against my field in the Psychiatry: An Industry of Death Museum.
Who I’m proud to have had as a research mentor.
Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009 Oct 28; 302(16): 1765-73. doi: 10.1001/jama.2009.1549. Erratum in: JAMA. 2009 Dec 2; 302(21): 2322. PMID: 19861668; PMCID: PMC3055794.
A.k.a. this study is really the heavy lifting by hand, analog version of what Dr. Insel recommends as his point number 2 for everyone.
As told to me when we worked together, Dr. Christoph Correll began collecting data for the SATIETY study when he was still a trainee. He spent weekends going to the homes of patients enrolled, doing blood draws himself, etc. These studies don’t just happen. They are decades of work by dedicated scientist physicians who are often doing completely other jobs at the same time. Like, you know, how residency is hard? Imagine personally collecting hundreds-of-patients-worth of data from kids and families at the SAME time. I personally went through every single paper response form for the data set to validate what I was seeing in the massive 3000-field JMP data set for my publication out of that data. 860 records (at the time)…real research is a lot of work!
A fools errand if ever there was one…
A 0.2 effect size—for Abilify augmentation—is measured in standard deviations. The effect size of SAINT treatment is 1.7. Yes, more effective than any medication for any condition in all of psychiatry. Thanks, my proposed 2023 Nobel prize winner in medicine, Nolan Williams, M.D.
Hypertension, obstructive sleep apnea, etc.
I went through the What If Ventures fellowship, and I think it’s a great program—but the predictable downside of letting a bunch of young people decide what should be disrupted is that the focus is on things that have impacted them. And they’re not old enough, on average, to have gained massive amounts of weight from antipsychotic augmentation yet. It’s just not on their radar. Young people are busy building businesses to be acquired by Pharma. They’re not gonna turn around and decide that the entire Pharma business model is all wrong… that’s just crazy talk. That makes you sound like some sort of anti-psychiatry lunatic. You’re never going to get a company funded with that attitude.
Advertised, in creepy coercive form, here:
This is such an important take! I am downloading it for future reference. Its salient points will be in my next presentation. We must be more aware of the long-term harms we are causing, especially since there are other options available.
As a now semiretired psychiatrist looking back at my career, the issue of weight gain on so called atypical antipsychotics was clearly an issue as they first became available. But we were so enthused to have options we tended to be less focused on this side effect than we should have been. Over time though, the question I began to ask myself over and over was, in the cases where there was only minimal benefit was it more prudent on the risk vs benefit scale to not treat with meds at all, even in some well documented cases of schizophrenia, in the presence of strong family support, minimal psychosocial improvement with meds, and determined noncompliance by the individual.
The second insight which seems obvious but yet somehow is overlooked, was that people become overweight when they eat, and they eat when they are hungry, and brain chemistry drives hunger. Talking down to overweight people as though there is some moral weakness in their hunger levels is unfair. Or trying to tell people they can just diet with enough willpower despite being uncomfortably hungry. Only now are we actually starting to understand how appetite works as we find ways to change satiety and appetite pharmacologically.