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December 24, 1997

Brain Serotonin Neurotoxicity and Fenfluramine and Dexfenfluramine-Reply

Author Affiliations

National Institute of Mental Health Bethesda, Md
University of Chicago Chicago, Ill
University of Maryland School of Medicine
Johns Hopkins University School of Medicine Baltimore, Md

JAMA. 1997;278(24):2142. doi:10.1001/jama.1997.03550240032024

In Reply.  —Dr Lipetz presents intriguing evidence for differences in the Trp/LNAA ratios of fenfluramine and dexfenfluramine users vs control dieters that, at least in part, may be related to the serotonergic neurotoxic effects of fenfluramine(s). The basis for the sex differences and his suggestion that tolerance to the anorectic effects of fenfluramine(s) may be related to the loss of brain serotonin terminals both merit further exploration. As we have discussed elsewhere,1,2 persistent tolerance after discontinuation of use of fenfluramines may signal brain serotonin neural injury.Dr Mattes raises the important question of whether classic psychostimulants might be safer than fenfluramine(s) for the purposes of weight loss. While this may be true for phentermine and possibly other amphetamine derivatives (eg, methylphenidate), issues other than potential neurotoxic effects (eg, abuse liability, tolerance) also need to be considered when evaluating drug safety.Drs O'Callaghan and Miller contest our assertion that the available data