Jose de Leon: Training psychiatrists to think like pharmacologists
Valproate Case 2 Safety


Hector Warnes’ comments on Michael Goldberg’s response to Jose de Leon’s reply to his comments


         Dr. Goldberg reminds us that most package circular and summary of product characteristics (SPC) provided by pharmaceutical companies are based on post-marketing reports. I guess they include all the adverse reactions found during the preclinical and controlled trials. I wonder whether the percentage of post-marketing reports increase after a decade of drug use (during which time the drug is usually being prescribed along with other drugs to most patients) to the point that it becomes difficult to determine which is an adverse event and which is an adverse reaction.

         Further, when prescribing a product the physician must inform the patient about the potential risks of treatment. If we are aware that the risk of an adverse reaction is 1 in 10 (very common) or 1% (frequent) or 1 in 1,000 (infrequent) or rare (1 in 10,000) or very rare (more than 1 in 10,000) we cannot obviously predict which adverse reaction might occur in which patient nor can we inform the patient of a dozen or so potentially dangerous effects or events. We cannot predict either that for this particular patient the reaction would correspond to the rare or the frequent categories. The legal requirement of informing patients pre-treatment might also create a negative placebogenesis even if the doctor underlines the fact that the benefits surpass the potential harm. Such a statement cannot be ascertained with anticipation when a patient with a particular pharmacogenomic profile has a rare but serious adverse drug reaction. Of course, unless all patients are tested for the pharmacogenetic or pharmacogenomic profile which would be very cumbersome.

         Finally, if after a decade or so of drug marketing the number of adverse events or adverse reactions have increased by 20 or 30 % we cannot be sure if that particular drug has more adverse reactions compared with the number of many other drugs given by the physicians where the adverse reactions or events are infrequently or rarely reported.


July 18, 2019