Weight Gain on Antidepressants, such as Monoamine Oxidase Inhibitors (MAOIs): Theoretical Implications

Weight gain on antidepressants like MAOIs (monoamine oxidase inhibitors) is a relatively common and frustrating side effect. What drives it? And what might the phenomenon tell us about the competing hypotheses about what regulates our weight?

The Caloric Balance Hypothesis says that a medication can only cause fat gain by changing the balance of calories eaten and "burned off."

The Lipophilia Hypothesis suggests that medications could cause overweight simply by deranging fat tissue metabolism -- by, for instance, changing insulin sensitivity or by causing the excess secretion of insulin. The lipogenic effect of insulin would cause us to accumulate more fat; this in turn would drive us to establish a positive caloric balance.

So which hypothesis about weight gain on antidepressants is better?

A few random Google searches about MAOIs and insulin and weight gain lead us to some very interesting articles:

1. Here's one from the American Journal of Physiology: "Inhibition of insulin release by substrates and inhibitors of monoamine oxidase."[1]

Unfortunately you can't view this PDF without "signing in," but the title is very suggestive, isn't it? It implies, perhaps, that these drugs can change insulin levels.

2. Here's another article from Endocrinology: "Dual action of antidepressant drugs on insulin release."[2]

The authors note:

"Experiments have been carried out to investigate the role of monoamine oxidase in the mechanism of insulin release... The data presented here clearly show that MAO inhibitors are capable of both potentiating and inhibiting insulin release..."

3. Here's another article: "Insulin secretion. Its regulation by monoamines and acid amyloglucosidase."[3]

Although we can't read the article for free, again the title alone seems to offer pretty compelling support for the Lipophilia perspective.

4. In case you're wondering, evidence of weight gain on antidepressants like MAO inhibitors abounds. For instance, check out: "Monoamine oxidase inhibitors weight gain."[4]

The authors state: "weight gain associated with antidepressant therapy is a common problem that often results in noncompliance."

Obviously, experts in the metabolic effects of MAOIs could no doubt do a far better job of building a pro-Lipophilia case. But even these randomly selected studies seem to build an impressive case that calories don't "count" after all.

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1. Aleyassine H, Lee SH. "Inhibition of insulin release by substrates and inhibitors of monoamine oxidase." Am J Physiol. 1972 Mar;222(3):565-9.

2. H. ALEYASSINE and ROBERT J. GARDINER. "Dual action of antidepressant drugs on insulin release." Endocrinology Vol. 96, No. 3 702-710.

3. Lundquist I. "Insulin secretion. Its regulation by monoamines and acid amyloglucosidase." Acta Physiol Scand Suppl. 1971;372:1-47.

4. TG Cantu and JS Korek. "Monoamine oxidase inhibitors weight gain." Drug Intelligence & Clinical Pharmacy: Vol. 22, No. 10, pp. 755-759.

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