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Could experimental weight loss drug, Lorcaserin cause depression?

(originally published on Arena Pharmaceuticals (Boston) has filed for approval of its experimental weight loss drug, lorcaserin. 

According to an Arena press release, “subjects taking lorcaserin twice a day, lost five percent or more of their weight after a year.” Arena states that the average weight loss for participants taking lorcaserin was 12.7 pounds in one year. According to the Arena website, lorcaserin, is a “lead drug candidate” and is one of the only two drugs listed in their “development pipeline.”

How Lorcaserin Works

Lorcaserin is an agonist; it initiates a physiological response when combined with a receptor in the brain, in this case, the hypothalamus. The hypothalamus controls body temperature, thirst, hunger, sleep and other “emotional” activity. The activation of this receptor (also known as 5HT) by lorcaserin will trigger serotonin and inhibit the production of dopamine.Dopamine is the chemical substance associated with our cognition, mood, attention and — quite possibly — motivation.

According to research published by the Proceedings of the National Academy of Sciences (PNAS), some suicide victims have an abnormally high number of 5HT receptors in the brain. Lorcaserin works as a selective, and efficacious agonist of the 5HT receptor. This means that obesity treatment involving lorcaserin could possibly cause depression via its activation of the 5HT receptor in the brain. “Sanofi-Aventis, Merck and Pfizer all discontinued work on experimental obesity drugs last year because of concerns that the drugs, which all worked by similar mechanisms, could contribute to depression and suicidal thoughts.” [New York Times]

Side Effects of Lorcaserin

  • upon discontinuation of lorcaserin treatment, lost weight is regained.
  • all groups received no diet or exercise instruction
  • groups regained weight more rapidly than they had lost.
  • main ingredient could lead to a large proportion of the anxiety, depression, and otherwise undesirable effects of hallucinogens.

The marketing of Lorcaserin

“Lorcaserin has the potential to become a targeted treatment option, with a compelling profile that could provide physicians with the confidence to use it as a baseline therapy for the majority of their patients,” this according to the Arena website. However, according to data gathered from an Arena “2006 Research and Development” sales presentation on lorcaserin (code name: BLOOM) there are unresolved issues, citing that “a longer study [is] needed for definitive echo safety analysis.”

For more info: Arena lorcaserin company press release (via Reuters)

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