SSRI Weight Gain: How This Side Effect Challenges Our Understanding Of What Makes Us Fat

SSRI weight gain has long been documented. Physicians often shrug off this side effect. Patients who feel happier eat more vigorously, they argue. But can increased appetite account for the effect? Not really, say researchers:

1. "Antidepressants such as... some serotonin reuptake inhibitors (SSRIs)... may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms."[1]

So if increased appetite alone can't explain what's going on, what DOES drive SSRI weight gain, and how might this discussion relate back to our big questions about what makes people fat and what's causing the obesity epidemic?

The Caloric Balance Hypothesis tells us that SSRI weight gain must be due to some impact on our intake and expenditure of calories. For instance, maybe these drugs stimulate appetite and/or slow metabolism, causing us to take in more calories, which then get deposited as fat.

The Lipophilia Hypothesis tells us something different. It tells us that, if a medication makes us fat, it must be doing something to our physiology -- perhaps changing hormonal balance in the body and thus driving the over-secretion of insulin, for instance.

So which theory is better?

A quick and cursory internet search pulls up some fascinating scientific articles regarding SSRIs, insulin, and weight gain and their various associations.

2. Here we have an article from 1999 about SSRI weight gain: "Selective serotonin reuptake inhibitors, Fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms."[2]

This is a study of SSRIs in mice. The authors found that two common SSRIs "elicited significant hyperglycemia" and suggested they did so by "inhibition of insulin release."

So, sure, this was a study done in mice, and thus it might have no relevance to human beings. But if SSRIs do cause weight gain, as many publications suggest, and they do cause insulin resistance and hyperglycemia, then doesn't this argue strongly for the Lipophilia interpretation as opposed to the Caloric Balance interpretation?

3. Here's another article from animal research: "The effects of the selective serotonin reuptake inhibitor fluvoxamine on body weight in Zucker rats are mediated by corticotrophin releasing hormone."[3]

4. Here's another interesting article about SSRI weight gain: "Adverse reactions to selective serotonin reuptake inhibitors: reports from a spontaneous reporting system."[4]

The authors note that body weight gain was indeed a side effect often reported by patients.

5. "Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors."[5]

The authors note:

"It has been suggested that weight gain associated with tricyclic antidepressants reflect actions on dopamine and histamine receptors. However a definitive cause is purely assumptive given the non-selective pharmacology of these agents."

In other words, these authors admit that it's difficult to identify a cause simply just because you see an association. The authors then discuss: "the apparent paradoxical affects of SSRIs on appetite" -- presumably "paradoxical" because the authors are thinking about weight gain through a Caloric Balance lens.

6. Here is another article: "weight gain on antidepressants" published in The Journal of Clinical Psychiatry in 2000.[6]

The authors tell us that:

"Weight gain is a relatively common problem during both acute and long term treatment with antidepressants, and it is an important contributing factor to noncompliance."

Interestingly, while the authors suggest that the weight gain "can either be a sign of improvement in patients who have weight loss or symptoms of depression or residual symptom in patients who overeat when depressed," they also admit that some of the weight gain "is likely to be a side effect of antidepressant treatment."

If you believe in the Caloric Balance Hypothesis, however, this theory about SSRI weight gain cannot be correct. "Calories In" and "Calories Out" alone regulate the body's fat stores. So if "antidepressant treatment" in and of itself -- as opposed to the establishment of a positive caloric balance -- drives fat accumulation, this is a huge contradiction. It can resolved only by admitting that Caloric Balance is wrong and that some version of Lipophilia is correct.

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References


1. Ness-Abramof, R., Apovian, C.M. Drug-induced weight gain Drugs Today 2005, 41(8): 547.

2. Jun Yamada, Yumi Sugimoto and Kiyo Inoue. "Selective serotonin reuptake inhibitors, Fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms." European Journal of Pharmacology Volume 382, Issue 3, 15 October 1999, Pages 211-215.

3. I Wieczorek, C Schulz, H Jarry and H Lehnert. "The effects of the selective serotonin reuptake inhibitor fluvoxamine on body weight in Zucker rats are mediated by corticotrophin releasing hormone." International Ôournal of Obesity. October 2001, Volume 25, Number 10, Pages 1566-1569.

4. Spigset O. "Adverse reactions to selective serotonin reuptake inhibitors: reports from a spontaneous reporting system." Drug Saf. 1999 Mar;20(3):277-87.

5. Harvey BH, Bouwer CD. "Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors." Clin Neuropharmacol. 2000 Mar-Apr;23(2):90-7.

6. FAVA M. "weight gain on antidepressants" The Journal of clinical psychiatry. New Strategies for Improving the Treatment of Depression. Round Table, San Francisco, California , ETATS-UNIS (15/10/1999).

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