The sEROtonergic pathway: a hERO for the brain, a zERO for the valves?

In medical school and ever since, we have been taught with the wisdom that pharmacological agents can heal, but also can harm. Medications or their metabolites that target the serotonergic pathways do not escape form this mantra. The last decades, several reports have suggested an association between serotonergic agents and valvular heart disease that eventually led to their withdrawal from the market. This was the case for the anorectic drugs fenfluramine and dexfenfluramine in the 1990s, and for the dopamine receptor agonist pergolide, a second-line Parkinson disease therapy, withdrawn in 2007 in the USA and in 2011 in Europe.1 2 As a large number of commonly prescribed medications such as antipsychotics, antidepressants, anxiolytics and antimigraine medications act on serotonergic mechanisms, concerns were and are raised that these approved agents might also cause drug-induced valvular heart disease (DIVHD). Most reports that have studied an association between serotonergic medications and valvular disease show an inherent risk of bias and confounding due to methodological issues such as study …