The Mefloquine Toxidrome: A Common Confounder of Mental Illness Among Returning Veterans?

Clinicians evaluating returning U.S. military veterans with certain psychiatric complaints need to be aware of the potentially confounding role of antimalarial neurotoxicity, said Remington Nevin, M.D., M.P.H., of Johns Hopkins University, at a workshop in the Military Track at APA’s 2014 annual meeting today, co-chaired by former psychiatry consultant to the Army Surgeon General, Elspeth Cameron Ritchie, M.D., M.P.H., a retired Army colonel.

Nevin’s work contributed to the FDA’s issuing an updated boxed warning for mefloquine in late July 2013, advising that psychiatric effects from the drug could last years after use and that certain neurological effects could be permanent. As early as 2012, travel medicine guidance from the Centers for Disease Control and Prevention had cautioned against the use of mefloquine in military settings, noting that the neuropsychiatric side effects of the drug could confound the diagnosis and management of PTSD and TBI.

Although mefloquine use has been significantly curtailed and even banned outright by some U.S. military units since the 2013 boxed warning, the lasting effects described by the FDA mean many military veterans may still be experiencing symptoms from mefloquine years after their last use of the drug.

Nevin noted that the syndrome of toxicity caused by mefloquine shares many features in common with agoraphobia and with many trauma- and stressor-related disorders, and may occasionally even have been mistaken for PTSD. Fortunately, the new DSM-5 criterion H, which excludes the diagnosis if “attributable to the physiological effects of a substance,” will help to ensure diagnostic specificity, particularly in military cohorts where exposure to the drug may frequently have overlapped with directly experienced traumatic events in Criterion A.

Nevin noted that in addition to taking a detailed antimalarial drug history when evaluating veterans with certain anxiety disorders, psychiatrists may wish to adopt a multidisciplinary approach including referring their patients to neuro-otologists, neuro-optometrists, or ENT physicians if symptoms indicate. Documenting neurological sequelae of the toxidrome, including disequilibrium, nystagmus, and vertigo, thought to be caused by subtle neurotoxic brainstem injury, can frequently aid in establishing the diagnosis of mefloquine toxicity even in the presence of common confounding psychiatric etiologies.