Phentermine May Increase Plasma Serotonin When Given With Fenfluramines

Phentermine has been used in the USA to treat obesity since at least 1961 and was widely used after 1992 in combination with fenfluramine.

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A study in 1997 suggested that this combination could be associated with heart-valve disease similar to that seen in the carcinoid syndrome or in patients who had taken ergotamine, as well as with pulmonary hypertension, previously described. It was suggested that these findings, were due to an increase in circulating serotonin.

Subsequently, the US Food and Drug Administration found heart-valve lesions among patients taking a fenfluramine without phentermine.

That phentermine inhibits the MAO (monoamine oxidase) which catabolises serotonin was well known in the early 1970s, but apparently this information never made its way onto the drug's label.

There is evidence that free plasma serotonin can damage vascular tissue and that its concentration is normally kept low by the action of the two high-capacity systems that remove it from the circulation-uptake into platelets and MAO.

If the fenfluramine and phentermine regimen did produce pulmonary hypertension and cardiac valve lesions then they might have been obviated had the Phentermine label within the US mentioned that the drug is an MAO inhibitor.

Such a mention would also warn physicians against combining phentermine with fluoxetine, flenfluramine, or other SSRIs.