Additional studies to investigate the mechanism for this pathology have not been performed, and the potential significance of this effect in humans has not been established.

Cardiovascular Changes in Dogs

In a one-year toxicology study, 5 of 10 beagle dogs receiving oral racemic citalopram doses of 8 mg/kg/day died suddenly between weeks 17 and 31 following initiation of treatment. Sudden deaths were not observed in rats at doses of racemic citalopram up to 120 mg/kg/day, which produced plasma levels of citalopram and its metabolites demethylcitalopram and didemethylcitalopram (DDCT) similar to those observed in dogs at 8 mg/kg/day. A subsequent intravenous dosing study demonstrated that in beagle dogs, racemic DDCT caused QT prolongation, a known risk factor for the observed outcome in dogs.

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