While anti-smoking drug Chantix can provide soothing feelings, its use has elicited suicidal thoughts in some people.

Courtesy Rob Lee/Flickr Two drugs that act on nicotine receptors are now being tested as antidepressants – offering hope to the millions of people who don't respond to traditional antidepressants.

Chantix, a pill that can help people quit smoking, and Inversine, a hypertension drug, appear to exert a soothing effect by blocking nicotine receptors in the brain. There's just one catch: Chantix may also exacerbate suicidal tendencies.

Chantix came on the market in 2006 and has recently been blamed for causing suicidal thoughts, prompting the FDA to issue not one, but two, advisories about the drug. That came after friends and family of Dallas musician Carter Albrecht blamed Chantix for the erratic behavior that led to his violent death. Quite a few smokers described worrisome emotional side effects on blogs and in the pages of New York Magazine.

But after Brown psychiatry resident Noah Philip gave one of his chronically downcast patients a prescription for Chantix to help break her smoking habit, he got an unexpected surprise. During their first follow-up appointment, she was smiling and felt great. When he learned that his colleagues had similar experiences, the young doctor knew that he was on to something.

To follow up on his revelation, Philip and his mentor Lawrence Price are conducting a study to test the mood-elevating effects of the medication. At Butler Hospital in Providence, Rhode Island they are giving depressed smokers Chantix in addition to their regular psychiatric medications. Over the course of eight weeks, Philip and Price will monitor the volunteers and pay close attention to their ability to enjoy life as well as unwanted side effects.

"At this point we haven't had any adverse events similar to those reported, but several people have become irritable," says Philip.

A 2006 study published in the New England Journal of Medicine revealed that half of all patients do not respond to conventional antidepressants, so new strategies to fight the disease are desperately needed.

Created by a team at Pfizer, Chantix can suck the pleasure out of smoking by blocking nicotinic acetylcholine receptors – neurological buttons that are usually pushed by tobacco products. Lightly stimulating those same proteins, the medication also creates a sensation similar to but weaker than the one created by tobacco products, which can cut down on withdrawal symptoms.

One thing is certain: The drug does not have an antidepressant effect for everyone. Since it may elevate the mood of some and causes intense feelings of sadness in others, a lab test that could predict how patients will respond to the pill would be invaluable. But until scientists understand the subtle biological variations that cause some people to feel miserable and others to have the opposite experience, that sort of personalized medicine will remain in the realm of science fiction.

"It would be very interesting to study what might be different about the patients who are reporting that they feel less depressed on Chantix," says Marina Picciotto, a professor of psychiatry at Yale University who studies nicotinic acetylcholine receptors. "It will also be interesting to see whether there is any difference in antidepressant response to Chantix between smokers and nonsmokers."

Scientists are confident that the simple act of kicking a nicotine addiction is not the underlying cause of the amazing mood improvements.

"Quitting smoking does not seem to help depression," says Tony George, a professor at the University of Toronto. "There is no evidence that nicotine or smoking causes depression. They seem to be behaviors that have common genetic roots."

George has tested the antidepressant-assisting effects of the blood pressure drug Inversine (mecamylamine), which blocks nicotinic receptors, but does not gently stimulate them like Chantix. Aside from saying that the combination seems to work on people who are unresponsive to traditional antidepressants alone, the addiction expert is not comfortable sharing his results until they are published.

George points out that studies have not confirmed the antidepressant qualities of Chantix, although he is cautiously optimistic. "I think there is lots of evidence to speculate that such a mechanism might be therapeutic in depression, at least as an adjunct to standard antidepressant treatments," George says.

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