ABSTRACT
Background: The adverse effects
of mefloquine and other quinoline antimalaria drugs can be severe and long-lasting. We believe that the trigger for these effects may be drug-induced
hepatocellular damage that causes, firstly, a spillage of retinoids into the circulation (and hence a direct toxic effect on the brain and other target
organs), and secondly, disruption of the liver-thyroid axis (and hence a
pattern of specific bipolar symptoms such as
is often seen in thyroid disease). Methods: We sought recently-published lay accounts of adverse effects
in users of quinoline antimalaria drugs, to test these lay descriptions
against our hypothesis on the likely pathogenesis of these effects. Results: We found six lay accounts that described four different experiences of adverse effects arising from the
prophylactic use of quinoline antimalaria drugs. All four travellers were healthy, at the start of travel. Two
of the travellers experienced severe psychoses, and one had a mild psychosis. The
fourth traveller, a serving US soldier,
killed 16 unarmed Afghan civilians. Analysis of these accounts shows that,
based on our hypothesis, all four travellers had at least one risk factor (most commonly, concurrent alcohol use), for developing a severe reaction to
their quinoline antimalaria drug. Our hypothesis therefore predicted a severe
adverse drug reaction in each of these four
travellers. We also identified a hitherto unrecognized risk factor for developing a severe reaction to quinoline antimalaria drugs—namely, the concurrent use of anabolic steroids. Conclusions: Lay accounts of drug adverse effects
can help initiate or further develop medical hypotheses of their pathogenesis. We advise that the quinoline class of antimalaria drugs should be prescribed cautiously, and that mefloquine should not now be prescribed for malaria
prophylaxis, under any circumstances whatsoever. Where persistent adverse
effects have resulted from the historical use of quinoline antimalaria drugs, we propose a five-point management strategy that we believe will in most cases cause symptoms to abate
rapidly: 1) stop taking the quinoline drug; 2) stop alcohol, and stop all other
liver-damaging drugs, including anabolic
steroids, hormonal contraception, hormone replacement therapy, recreational drugs, antidepressants,
anxiolytics and hypnotics; 3) maintain good hydration, using
non-fluoridated drinking water; 4) temporarily eliminate dietary vitamin A; as an additional and optional therapeutic measure, 5) lower the concentration of circulating
retinoids through phlebotomy, plasmapheresis or hirudotherapy.