Weight Gain on Antidepressants like Tricyclics (TCAs): Can it Give Us Clues about the True Cause of the Obesity Epidemic?

For decades, clinicians have documented weight gain on antidepressants as a common but undesirable side effect of treatment. What's driving this phenomenon? More profoundly, what could the root cause of this weight gain tell us about diet and nutrition?

The Caloric Balance Hypothesis tells us that weight gain on antidepressants like TCAs can only result from eating too much or from not burning off enough calories - presumably through exercise.

The Lipophilia Hypothesis has a profoundly different point of view. It tells us that anything that might disturb the hormonal balance of our fat tissue can theoretically drive weight gain. So, for instance, if a medication increases the insulin sensitivity of the adipose tissue, this could drive the storage of fat in fat cells.

A Google search about TCAs, weight gain, and insulin yields some interesting medical articles. Let's see whether these articles can confirm or disconfirm our hypotheses.

1. Our first article -- "Weight gain. A side effect of tricyclic antidepressants" -- was published in October of 1984.[1]

In this study of 40 patients on tricyclics, over the course of about half a year:

"There was a mean weight increase of 1.3 to 2.9 pounds a month, which led to an average total weight gain of 3 to 16 pounds, depending on drug, dose and duration. These weight increases were linear over time and were accompanied by marked increases in the preference for sweets."

Okay, so these drugs seem to be able to drive body weight gain. But what's behind it?

2. Here is a paper that investigates how antidepressants impact the metabolisms of mice: "Effect of some antidepressants on glycaemia and insulin levels of normal glycemic and alloxan induced hyperglycemic mice."[2]

The researchers looked at how TCAs impacted insulin and blood glucose levels of mice and found that "tricyclics might induce an important decrease in glucose tolerance and worsen the control of diabetic patients."

3. Perhaps more telling about weight gain on antidepressants is this article: "The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms."[3]

The authors set out to: "synthesize results from investigations reporting on the effects of antidepressants and glucose insulin homeostasis." They found that "some antidepressants exert a clinically significant effect on metabolism relevant to both therapeutic outcome and adverse events." They also found that certain drugs influenced insulin sensitivity.

So what's going on here? The answer is clear: the Caloric Balance Hypothesis is, once again, getting refuted.

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References


1. Berken GH, Weinstein DO, Stern WC. "Weight gain. A side effect of tricyclic antidepressants" Affect Disord. 1984 Oct;7(2):133-8.

2. Erenmemisoglu A, Ozdogan UK, Saraymen R, Tutus A. "Effect of some antidepressants on glycaemia and insulin levels of normal glycemic and alloxan induced hyperglycemic mice." J Pharm Pharmacol. 1999 Jun;51(6):741-3.

3. McIntyre RS, Soczynska JK, Konarski JZ, Kennedy SH. "The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms." Expert Opin Drug Saf. 2006 Jan;5(1):157-68.

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