Mayo Clinic Counterpoint to FDA on Citalopram

The Mayo Clinic came out with their recommendations on what to do about the FDA's warning about citalopram.  By their own description they are more liberal with regard to their citalopram recommendations and more conservative regarding escitalopram.  I have previously reviewed the problem here and concluded that there is really a lack of data available on the likelihood of electrocardiogram abnormalities during normal clinical use and if citalopram is as cardiotoxic as the FDA is describing it - we should treat it more like a standard antiarrhythmic drug and used flecanide as an example.

For all practical purposes that would include baseline ECGs, ECGs at the max dose and taking it up one more level from either the Mayo Clinic or the FDA - a stress test looking for QTc prolongation at higher heart rates.  The other elements in the Mayo recommendations based on history and physical examination and expecting some physician knowledge of drug metabolism are fairly standard.  I thought it was interesting that they did not mention checking plasma levels of the drug especially in complex cases (eg. a patient with cirrhosis) who only responds to higher than recommended doses of the drug.  Regarding the statements:  "Selective serotonin reuptake inhibitors cannot simply be substituted for one another, not even escitalopram for citalopram."  That is generally true and where are these guys in the battle against PBMs saying that these drugs are all equivalent?  I have not found any patient that responded selectively to citalopram and not escitalopram.  I have generally been able to convert patients to an equivalent amount of escitalopram the next day.

Both the Mayo Clinic and the FDA are silent on molecular approaches to solving this problem and screening patient for potential risk before they are started on either drug.  The Mayo Clinic offers testing for cytochrome P450 genotypes.  The genetic basis for hereditary prolonged QTc intervals has been a hot topic of research over the past decade.  It is probably time to expand the search for additional genotypes that place people at risk during specific drug therapies.  Until then we have only very approximate methods of determining the at - risk population and keeping them safe and the Mayo recommendations are more reality based than the FDA.

I think it would also be possible to estimate the risk associated with taking citalopram across the entire population.  In fact, at this point the FDA seems to have the data to estimate the risk of any QTc effect at all to the risk of torsade de pointes - the most significant arrhythmia.  I think it is very important for patients making the decision to have this number and if I can provide numbers on rare but serious antidepressant complications like serotonin syndrome, a federal agency with more perfect information and no patient care responsibility can do better.

George Dawson, MD, DFAPA

Sheeler RD, Ackerman MJ, Richelson E, Nelson TK, Staab JP, Tangalos EG, Dieser LM, Cunningham JL. Considerations on safety concerns about citalopram prescribing. Mayo Clin Proc. 2012 Nov;87(11):1042-5.

FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses.