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"A lesson learnt: the rise and fall of Lariam and Halfan". J R Soc Med. 4 (4): 170–4.

Lariam (pharmacological name mefloquine) is an anti-malaria drug discovered by the US Army shortly after the Vietnam War, and subsequently marketed worldwide by F. Hoffmann-La Roche. The first reported trials of mefloquine were in prisoners, and were performed at the Joliet Correctional Center, Illinois, in 1975, and at the Maryland House of Correction in 1976.

…..There is no question that safe and effective antimalaria drugs were needed in the second half of the twentieth century, once it became apparent that the Plasmodium had developed resistance to the mainstay of antimalaria therapy, namely chloroquine. Chloroquine resistance was observed first in Thailand in 1957, then on the Colombian-Venezuelan border in 1959, and in Kenya and Tanzania in 1978. Within a decade of Lariam and Halfan being marketed, however, the safety of both these novel agents was in doubt.

Though still prescribed in most countries, both for preventing and treating malaria, Lariam is now known to cause neurotoxicity. This unexpected property came to prominence in the mid-1990s, when national pharmacovigilance centres, initially in Europe, began to receive recurring reports of neuropsychiatric adverse effects caused by this new antimalaria agent. In the Netherlands during 1998 and 1999, mefloquine was respectively the most and the second most cited drug in spontaneous reports of drug-related illness made to the Lareb Pharmacovigilance Foundation. Around the same time, it was reported that 60% of all the mefloquine occurrences notified to the WHO's Uppsala Monitoring Centre cited neuropsychiatric disturbance secondary to the drug.

Belatedly, three randomized controlled trials were carried out in healthy volunteer populations, and were reported between 2001-2003. The studies confirmed mefloquine's potential for causing psychological illness, and all three study reports described an excess of neuropsychiatric adverse effects in the mefloquine arm.

Around the same time an analysis of the cause of illness in 4524 travellers returning from sub-Saharan Africa to the northern hemisphere found that, excluding diarrhoea and fever as causes, mefloquine was the fifteenth most common cause of post-travel illness. A case control study of 564 Dutch travellers between 1997 to 2000 found a threefold increase in the incidence of psychiatric events with mefloquine use (OR 3.5, 95% CI 1.4-8.7), and a very high risk of psychiatric events in women users of the drug (OR 47.1, 95% CI 3.8-578.6).

A survey of the recent literature shows that mefloquine has been causally associated with 19 deaths in users, including three suicides