Anti-smoking drug Zyban is a form of bupropion
Obese patients who took a medication called bupropion hydrochloride - a form of which Zyban, is used to help people give up smoking - lost significant amounts of weight over a 24-week period.
Follow-up research showed that the patients who continued taking the medication for another 24 weeks kept the weight off.
A total of 227 patients completed the initial 24 weeks of the course, and 192 completed the full 48 weeks.
More than 200 clinically obese men and women took part in the study. None of them were clinically depressed.
The people who combined the medication with diet and exercise lost significantly more than those who just followed the diet and exercise regime.
Those who took 400mg/day of Bupropion lost a greater percentage of their initial body weight than those who took 300mg/day.
Some patients who took the medication experienced side effects such as headache, dry mouth and diarrhoea.
Lead researcher Professor James Anderson, of the University of Kentucky College of Medicine said: "We are encouraged by these preliminary results in non-depressed obese patients.
"Even modest weight loss, if maintained, could produce significant health benefits."
Other drugs
Professor Ian MacDonald, an expert in metabolic physiology at Nottingham University, told BBC News Online that Prozac had also shown promise as a potential treatment for obesity.
Another drug Sibutramine, which is currently used to treat obesity, was initially developed as an anti-depressant.
Professor MacDonald said: "It is not surprising that anti-depressants help some people lose weight. They act to improve mood and perceptions of self-worth so that people are better able to yes I can stick to this diet.
"But whether they will work for all obese people is another matter."
Professor MacDonald said there was also some evidence to suggest that antidepressants acted on the same areas of the brain that control food intake and appetite.
The results of the study were presented at a conference on nutrition in San Diego on Monday.