The Stress-Antidepressant-diet (SAD) Paradigm and Weight Gain

Suhyun Lee, Martin Lewis, Claudio A. Mastronardi, Rachel Li, Paul Smith, Julio Licinio, Ma-Li Wong

Research output: Contribution to conferencePoster


Background: Antidepressants are the most frequently prescribed class of drugs; about 264 million antidepressant prescription were issued in the US in 2011. The use of most antidepressants is associated with weight gain; however, the pathophysiogical mechanisms of this association are still unknown. Our lab has developed an animal model that addresses “paradoxical weight loss” by investigating the interactions between short-term exposure to stress, antidepressant administration and exposure, and long-term exposure to an obesogenic high-fat diet.

Methods: Male Sprague-Dawley rats are subjected to the following paradigm: Short-term exposure to recurrent restraint stress and antidepressants for 2 weeks, followed by long-term high-fat diet intake, were studied for 295 days. We have classified animals as obesity-prone (upper 50% of body weight) or obesity-resistant (lower 50% of body weight). On study day 295, animals were sacrificed and various organs were collected and weighed. Measurements: Body weight, food intake ratio, behavioural testing, and bone weight.

Results: Obesity-prone rats treated with fluoxetine (RFX) had increased body weight, in comparison to the control group treated with saline (RC) and non-restraint control group (NRCF). The RFX and the imipramine treated group (RIM) groups had significantly lower food intake ratio in comparison to the non-restraint control group (NRCF). The obesity-prone RFX rats had significantly longer body length in comparison to the NRCF, RC and RIM groups. The obesity-prone RFX and RIM rats had significantly larger body circumference in comparison to two control groups. The RFX group were significantly less anxious and had heavier bones.

Conclusions: Our data suggest that the association between stress, exposure to antidepressant treatment, and the long-term intake of an obesogenic high-fat diet is associated with greater weight gain, bone weight and body length in obese-prone RFX rats. We show that animals with antidepressant exposure had a greater degree of weight gain after long-term exposure to an obesogenic diet than animals on the same diet, but without exposure to antidepressants. We advance here the novel concept that antidepressant exposure represents a long-term risk factor for obesity and present the testable hypothesis that antidepressant exposure might be a major hidden contributor to our current obesity epidemic.
Original languageEnglish
Publication statusPublished - Dec 2015
Event54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) - Hollywood, United States
Duration: 6 Dec 201510 Dec 2015


Conference54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP)
CountryUnited States

Cite this

Lee, S., Lewis, M., Mastronardi, C. A., Li, R., Smith, P., Licinio, J., & Wong, M-L. (2015). The Stress-Antidepressant-diet (SAD) Paradigm and Weight Gain. Poster session presented at 54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP), Hollywood, United States.