Anti Depressants and Weight Gain:
Can the Ultimate Cause be That These Drugs Drive the Excess Secretion of Insulin?

The phenomenon of anti depressants and weight gain is real and significant.

According to a recent WebMD article: “experts say that for up to 25% of people, most anti depressant medications--including the popular SSRI (selective serotonin reuptake inhibitor) drugs like Prozac, Lexapro, Paxil, and Zoloft--can cause a weight gain of 10 pounds or more.“

Why? What about these medications causes some people to gain weight?

The Conventional Theory

Most researchers--whether they study obesity science or psychopharmacology--assume that when it comes to weight gain, “calories count.” This is an obvious idea to most people. We assume it as a first principle--a law of nature that’s carved in stone.

But in actuality, it is merely a theory about how the world works. And this theory derives from the First Law of Thermodynamics, which requires that energy taken in by the body equal the energy coming out of the body. Hence:

Energy Stored (presumably as fat) in the Body = Calories In - Calories Out

Almost everyone assumes (in the words of science writer Gary Taubes) an arrow of causality for this equation. In other words, we treat the “=” sign as a “←” sign implicitly. Thus the energy balance equation becomes:

Energy Stored in the Body ← Calories In - Calories Out

Once we look at the equation this way, we see that overeating (raising Calories In) and underexercising (lowering Calories Out) makes the right side of the equation bigger. This positive caloric balance, as it is known, then drives us to gain energy in our body, presumably as fat.

Whether you’ve thought about anti depressants and weight gain in this way or not before, this is how obesity researchers think about it. So, it’s important to understand their derivation.

To explain the relationship between anti depressants and weight gain, according to this theory, you must start from the perspective of: “how do these medications change calorie balance?” So your thinking will tend to be along the lines of the following:

Anti depressants → changes in caloric balance → changes in the amount of fat you have

The upshot is that the traditional explanations about anti depressants and weight gain tend to focus on how these meds impact appetite and metabolism. It is presumed that the meds perhaps increase appetite (driving up Calories In) and/or slow down metabolism (driving down Calories Out).

When you look at the scientific literature about anti depressants and weight gain, this kind of thinking pops up everywhere.

For instance, one popular theory is that anti depressants make people happier; and happier people tend to eat more. (This line of thinking conveniently ignores the fact that depressed people often turn to food for comfort, but that’s neither here nor there).

The aforementioned WebMD article quotes a PhD named Jack Fincham, author of a book called The Everyday Guide to Managing Your Medicines, who proposes an explanation along these lines: “It might be a situation where someone feels so much better when taking anti depressants that lots of things suddenly start feeling more pleasurable to them, and food is just one of them. So, in this instance, they may actually be overeating and not even realize that they are doing so.”

In other words, the meds cause an increase in appetite, which causes an increasing in Calories In, which causes the weight gain.

Fincham offers another popular explanation--namely that the meds somehow impact Calories Out as well. Here he is again: “I have had patients who swear that they are not eating anymore, but still gaining weight, so this tells us there is some kind of metabolic influence going on; I have also had patients tell me that they are not only more hungry and eating more, but the medicines are encouraging a carbohydrate craving that is hard to control, so we know appetite also plays a role.”

Okay, so these comments may seem relatively obvious and innocuous. But it’s important to distill down what this conventional wisdom tells us. It tells us that anti depressants and weight gain occurs because the meds impact calorie balance FIRST--by driving up Calories In or by driving down Calories Out.

We believe this point of view (also known as the “caloric balance hypothesis”) is flawed in many ways.

But rather than rehash the arguments, which you can read elsewhere on this site, we want to offer some counterevidence to challenge this conventional view.

1. Many studies show that the relationship between anti depressants and weight gain happens even when patients do not overeat and or decrease their activity.

2. Anecdotal evidence also suggests as much. We will now pull some quotes from a single message board about a single anti depressant to illustrate how powerfully this anecdotal testimony seems to refute the caloric balance explanation about anti depressants and weight gain. (These quotes all come from the website

BabbaJean (posted on 5/10/2005) : “I too gained weight while on Zoloft. I was thin, so a few extra pounds didn’t hurt. But, after six months, I hadn’t changed my diet, nor my workout. I am extra careful not to eat too much and always exercising. Nevertheless, I gained 20 pounds in six months. That’s more than I gained while pregnant. Today, I weigh as much as I did when I had my baby! Talk about depression! Although my doctor told me it isn’t the Zoloft, I know differently. My body chemistry is completely whacked! I feel it, I know it!”

Boo91 (posted on 5/25/2005) echoed this perspective: “I am so glad to hear that someone else has had a weight gain problem with Zoloft. I started taking Zoloft about 15 months ago and I have gained 20 pounds. None of my clothes fit me anymore. My diet has not changed and I exercise more than ever. I could not understand why I was gaining weight instead of losing or maintaining. At least, I have an explanation now. I am depressed because my clothes don’t fit. I am weaning myself off of Zoloft now. I am wondering if anyone knows how long it takes to have your metabolism return to normal or if it ever does? ”

Nanas Mama (posted on 8/27/2005) . I started taking Zoloft almost two years ago, when my daughter was three months old. I began experiencing increased anxiety. My doctor started me on 50 milligrams of Zoloft a day and after about six weeks, I started feeling better. Over the past few years, I have put on a considerable amount of weight (about 15 to 20 pounds). During that time, I did not change my eating habits or exercise routine. In fact, I began step aerobics/kickboxing class three months ago and have only gained more weight (although I realize some of that may be muscle).

What’s going on here with these patients? Are they freaks? Are they confabulating? Is this relationship between anti depressants and weight gain inexplicable by the laws of physics? If these people are not changing their caloric balance--or even changing it in a negative way by reducing calories and exercising more--then why are they gaining so much weight?

An Alternative Explanation

As we have vigorously argued elsewhere, the energy balance equation that we spoke about earlier can be interpreted in a different way. We all assume that caloric balance controls how much energy we store. But the First Law of Thermodynamics does not necessarily mandate this. It could be that energy balance controls caloric balance! The causality gets reversed, as Gary Taubes has pointed out. If this is the case, this gives us an easy way to explain weight gain and anti depressants. Here it is:

Medications → impact hormones such as insulin → changes the amount of energy stored in the body → changes caloric balance

In other words, these meds do NOT make us hungrier or slow down our metabolisms directly. They may ultimately do so, of course, but only indirectly by influencing fat tissue metabolism.

How do they do this?

Well, when you look at things through the lens of this other hypothesis, you have to consider what’s going on with the hormone insulin. Since insulin is critical for the regulation of the fat tissue, anything that might impact insulin levels should ultimately impact weight gain.

We did some googling and found many scientific articles that imply that anti depressants can adversely impact insulin levels, like this hypothesis suggests.

Consider this article from the November 2007 issue of Molecular and Cellular Neuroscience: “Anti depressants induce cellular insulin resistance by activation of IRS-1 kinases.” The authors write in the abstract that: “certain selective serotonin reuptake inhibitors (SSRIs) induced the clinical and biochemical manifestations of the metabolic syndrome by as yet unknown mechanism… These results implicate selected SSRIs as inhibitors of insulin cycling and as potential inducers of cellular insulin resistance.”

So, there you have it: an explanation for anti depressants and weight gain!

The meds create insulin resistance. The insulin resistance leads to the abnormal accumulation of fat in the fat tissue. The accumulation of excess fat drives up appetite and drives down metabolism. The meds don’t make us fat because they work on appetite or metabolism; they make us fat because they cause hyperinsulinemia. That’s our theory.

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