Table 3 Profile of centrally acting anti-obesity products withdrawn because of associated deaths over the last 50 years

Aminorex

• First introduced in 1962

• Became available within 3 years of introduction as an over-the-counter weight loss pill

• Between 1965 and 1972, there was an alarming increase in the incidence of primary pulmonary hypertension [52]

• The pulmonary hypertension epidemic ended in 1972 following the withdrawal of aminorex from the market

Benfluorex

• Approved in 1976 as an add-on treatment in obese patients with diabetes mellitus

• Cases of valvulopathy attributed to its use began to appear from 2003

• Was withdrawn in 2009 following an epidemic of valvulopathy attributed to its use

• Several deaths reported

• To date, more than 3000 hospitalizations and at least 1300 deaths attributed to its use in France alone [53]

Fenfluramine

• First approved in in 1973

• Reports of pulmonary hypertension first appeared in 1981

• Several other case reports subsequently published

• Epidemiological studies showed an association between fenfluramine and pulmonary hypertension [54]

• Withdrawn worldwide in 1997

Methamphetamine (desoxyephedrine)

• First introduced in 1944

• Within 10 years of its introduction, cases of its misuse had been reported

• By the early 1970s, reports of its abuse as an anorectic were reported [55]

• Was withdrawn in the USA and other countries in 1973

• Several cases of cardiac abnormalities related to its abuse have subsequently been reported

Phentermine

• First approved in 1959

• Several cases of lung phospholipidosis in animals and humans reported thereafter

• Reports of death began to appear in 1974 [56]

• Withdrawn from most countries where it was marketed in 1981

• Still available for short-term management of obesity in the USA

Rimonabant

• Approved in Europe in 2006 for obesity treatment

• Within 1 year of approval, concerns were expressed about the risk of depression and suicide associated with its use [57]

• Five deaths attributed to its use in the UK [58]

• Was withdrawn in 2007

Sibutramine

• Approved in 1997 in the USA and Europe in 2001

• Within a year of its European approval, serious cardiovascular adverse reactions were reported, resulting in temporary withdrawal in Italy [59]

• Several cases of severe cardiovascular adverse reactions, including deaths, were subsequently reported [60]

• Withdrawn in Europe and USA in 2010