They say patients who take Champix are also more prone to attempted suicide, suicidal thoughts and depression than those who use nicotine patches and gums.
Champix, which was prescribed more than one million times in Britain last year, has previously been linked to heart attacks, strokes, unprovoked violence and blackouts.
Last night Curt Furberg, the professor of public health sciences behind the latest study, said: ‘The risks simply outweigh the benefits.’
Dr Furberg and colleagues analysed the number of serious side-effects of anti-smoking treatments reported to the U.S. drugs watchdog between 1998 and 2010.
Champix, which is also known as varenicline and sold in the U.S. as Chantix, topped the table, despite only having been on sale for four of the years studied. Ninety per cent of reports of depression or suicidal behaviour, including suicide, related to the drug.
This compared with 7 per cent for another drug, Zyban, and 3 per cent for patches, gums and other nicotine replacement products, the journal PLoS ONE reported.
Dr Furberg, from Wake Forest University in North Carolina, would like the drug to be banned but accepts this is unlikely.
Instead he said: ‘Champix should be the last resort. You should give counselling to help people quit and if you need medication use nicotine replacement or Zyban.
'If you give Champix, keep track of the person’s mental status.’
British research published this summer linked the drug to heart attacks and strokes. A review of more than a dozen studies found that smokers who tried to quit using Champix were almost twice as likely to be taken to hospital in the next year than those who took dummy pills.
Champix has been linked to 80 deaths since its launch in Britain in 2006, including 39 suicides.
There have also been hundreds of reports patients experiencing suicidal thoughts.
Britain’s drugs watchdog, the Medicines and Healthcare products Regulatory Agency, said all medicines have side-effects and linking a reaction to a drug does not prove it was caused by the drug.
A spokesman added: ‘The MHRA, with other EU member states and the European Medicines Agency, will carefully consider this new study to see whether further advice to health professionals and patients on the use of varenicline is required.’
Pfizer, which manufactures Champix, said leaflets in the packets warn that some users have suffered depression, suicidal thoughts and behaviour or have attempted suicide.