Mefloquine prescriptions in the presence of contraindications: prevalence among U.S. military personnel deployed to Afghanistan, 2007.

Pharmacoepidemiology and Drug Safety 2010;19:206-210.

For safety reasons, the anti-malaria drug mefloquine is contraindicated in patients with certain mental health conditions, such as depression, in whom it may increase the risk of serious adverse events including suicide. This research merged DoD deployment and health databases with pharmacy data to explore whether, and how often, mefloquine had been prescribed to service members for whom it was contraindicated. This research found that 1 in 7 service members with contraindications had recently been prescribed mefloquine. Its publication preceded significant improvements in mefloquine policy within DoD .

Low validity of self-report in identifying recent mental health diagnosis among U.S. service members completing Pre-Deployment Health Assessment (PreDHA) and deployed to Afghanistan, 2007: a retrospective cohort study.

BMC Public Health 2009;9:376.

Despite efforts at improving post-deployment screening to identify mental health conditions such as PTSD, pre-deployment screening forms have remained unchanged since 1999. This research examined how accurately these forms identified disqualifying mental health conditions, and found that many service members with disqualifying conditions are erroneously deployed through current methods. This research confirmed concerns first raised in the popular press. Its publication preceded sweeping changes in pre-deployment screening and deployment-limiting medical policies.

Mental health standards for combat deployment.

Psychiatric Services 2011;62:805.

Despite nearly ten years of combat, relatively few publications in the mental health literature describe the effectiveness of military pre-deployment mental health screening standards and practices. Despite evidence in the literature of deficiencies noted years earlier, compliance with current military screening standards remains suboptimal, and evidence suggests that medical providers performing pre-deployment screening remain mostly unaware of the mental health histories of the deploying personnel that they evaluate. This Letter to the Editor summarizes and comments on recent published research, and encourages greater efforts towards compliance with policies designed to identify and restrict from deployment those at-risk personnel who do not meet current mental health standards.

Mefloquine neurotoxicity and gap junction blockade: Critical insights in drug repositioning.

Neurotoxicology 2011;32:986-987.

In recent years, the antimalarial drug mefloquine has become well-characterized as a potent neurotoxin and has been demonstrated to produce blockade of neuronal gap junctions, causing significant psychotropic effects. Owing to its toxic properties, mefloquine is being investigated for the treatment of brain tumors, progressive multifocal leukoencephalopathy, and other potentially life-threatening conditions. This Letter to the Editor summarizes recent research on the neurotoxicity of the drug and comments on the need for additional research to better understand and characterize these toxic effects.

Hallucinations and persecutory delusions in mefloquine-associated suicide. (In Press).

American Journal of Forensic Medicine and Pathology.

The antimalarial drug mefloquine has been linked to spectacular cases of suicide and suicide attempt, but until recently the pathophysiology underlying this association has been unclear. This Letter to the Editor comments on a recent case report of a stunning suicide by skull stab wounds associated with mefloquine, and references recent biological evidence suggesting that among susceptible individuals, mefloquine may induce a dissociative hallucinogenic state that mimics phencyclidine (PCP) toxicity. Such evidence provides insight into the known epidemiological association of mefloquine with acts of violence, and into earlier ecological and case-series reports of suicide associated with the drug.

Investigating channel blockers for the treatment of multiple sclerosis: Considerations with mefloquine and carbenoxolone.

Journal of Neuroimmunology 2012;243:106-107.

Although neurotoxic, mefloquine is a potent immunomodulator and has been demonstrated to block connexin gap junction intercellular communication and pannexin hemichannels. Recently, a related gap junction channel blocker, carbenoxolone, has shown intriguing potential against the neuroimmune disorder multiple sclerosis. This Letter to the Editor comments on the potential utility of investigating mefloquine for this indication, but cautions on the need to be alert for the possibility of serious neuropsychiatric adverse effects with any such treatment.

Pharmacokinetic considerations in the repositioning of mefloquine for treatment of progressive multifocal leukoencephalopathy. (In Press).

Clinical Neurology and Neurosurgery.

Mefloquine has shown intriguing therapeutic potential against JC virus infection and progressive multifocal leukoencephalopathy, yet recent trials of mefloquine have reportedly demonstrated disappointing results for this indication. This Letter to the Editor comments on the potential significance of heterogeneity in mefloquine pharmacokinetics and posits that host genetic or pharmacologic factors may contribute to variation in brain accumulation of mefloquine and may thus underlie the differential response to treatment observed across recent case reports.

Limbic encephalopathy and central vestibulopathy caused by mefloquine: A case report. (In Press).

Travel Medicine and Infectious Diseases.

Despite over 20 years of licensed use, the pathophysiological mechanisms underlying mefloquine’s neuropsychiatric and physical side effects and the clinical significance of the drug’s neurotoxicity have remained poorly understood. In this report, an adverse reaction to mefloquine chemoprophylaxis is described characterized by prodromal symptoms of anxiety with subsequent development of psychosis, short-term memory impairment, confusion and personality change accompanied by complaints of disequilibrium and vertigo, with objective findings of central vestibulopathy. This report is the first published description of this idiosyncratic neurotoxic syndrome.

Mefloquine blockade of connexin 36 and connexin 43 gap junctions and risk of suicide.

Biological Psychiatry 2012;71:e1-2

Recent studies have demonstrated a significantly reduced expression of the gap junction protein connexin 43 (Cx43) in the dorsal lateral prefrontal cortex of suicide completers. Mefloquine has been associated in the medical literature with often spectacular cases of suicide and suicide attempt and is known to effect a potent blockade of Cx43 and connexin 36 (Cx36) gap junctions. This Letter to the Editor comments on evidence that mefloquine blockade of gap junctions may modify a host of behaviorally relevant processes in regions of the brain with significant Cx36 expression, including the reticular activating system, ventral tegmental area, hypothalamus, hippocampus, and amygdala; and discusses the likely role of Cx43 gap junction blockade in contributing to these effects.