Article 2 — What Two Regulators Concluded

The firmest ground in this series — what the FDA and EMA concluded about mefloquine.

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Versión en español: Artículo 2 — Lo que concluyeron dos reguladores

Drug regulators are not advocates. They are institutionally cautious, procedurally slow, and structurally disinclined to make claims they cannot defend. When a regulator revises a label to add a warning, it has usually been persuaded by evidence it spent years resisting.

This matters for what follows. The strongest support for the proposition that certain anti-malarial drugs can cause lasting neurological and psychiatric harm does not come from campaigners or litigators. It comes from the United States Food and Drug Administration and the European Medicines Agency, in documents written for clinicians, in language chosen to be conservative.

The boxed warning

In July 2013, the FDA required a boxed warning on the label for mefloquine — the most serious warning the agency issues. The warning stated that neuropsychiatric adverse reactions can persist long after mefloquine has been discontinued.

Vestibular symptoms — dizziness, loss of balance, ringing in the ears — could in some cases be permanent. The FDA also directed clinicians to substitute another drug at the first sign of psychiatric or neurologic symptoms.

The European review

In 2014 the European Medicines Agency found evidence supporting a causal relationship between mefloquine and long-lasting, even persistent, neuropsychiatric effects — with no identifiable risk factors permitting prediction of who is at risk.

Only the advice — to stop taking mefloquine if neuropsychiatric reactions or changes to mental state occur — can be given as a precautionary measure.

What these findings do not establish

Regulatory findings describe population-level risk. They do not establish causation in any individual case, and they do not explain the mechanism — the subject of the next article.

Two national authorities reviewed the evidence on long-term causation in 2017 and reached different conclusions: Australia's Repatriation Medical Authority and Health Canada. Article 3 covers this dissent in full.

Why this is the starting point

What the regulators established is limited but solid: mefloquine can cause serious neuropsychiatric effects; those effects can outlast the period of use; some may be permanent; and no one can predict in advance who is at risk.

Everything this series argues afterward is weaker than that.