Brain Serotonin Neurotoxicity and Fenfluramine and Dexfenfluramine

James P. O'Callaghan, PhD; Diane B. Miller, PhD
JAMA. 1997;278(24):2141-2142. doi:10.1001/jama.1997.03550240031022.
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To the Editor.  —In their review, Dr McCann and colleagues1 conclude that fenfluramines damage brain serotonin neurons. They define serotonin neurotoxicity as "axotomy (ie, preterminal axon loss) of serotonin neurons in the central nervous system." Nowhere in their review do they provide evidence that fenfluramines do in fact cause axotomy; rather, they cite studies documenting what already is widely known: administration of high dosages of fenfluramines to experimental animals redices forebrain serotonin and associated markers.Decrements in serotonin markers cannot be equated with damage to serotonin neurons in the absence of evidence for underlying neuropathology. The presence of gliosis constitutes 1 such index of neuropathology. In our studies,2.3 in which we observed 15% to 70% decrements in brain serotonin following high-dose dexfenfluramine regimens, we did not observe increases in the content of glial fibrillary acidic protein (GF AP), a biomarker of gliosis. Contrary to the suggestions of McCann et al, our


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