The Importance of Electrocardiography In Psychiatric Practice....

The US Preventive Services Task Force came out with general recommendations for resting and exercise electrocardiography a few days ago in JAMA Cardiology.  I posted the above comments on Twitter to emphasize the importance of the ECG in psychiatric practice.  I was also pleased to hear the word I frequently hear when patients, families, and other staff question the need for electrocardiography and my refusal to start of continue certain medications without seeing that ECG. That word is that the ECG is an expensive test and why do we want to incur the additional expense?  It is not an expensive test and the information it yields for the money spent is high.  The actual guidelines are available free online and if you are a psychiatrist or any other practicing physician I encourage you to read them.

The interesting aspect of this publication is that the accompanying editorial by Joseph S. Alpert, MD is more informative that the USPSTF document.  The conclusion of the USPSTF document is that screening asymptomatic individuals with resting or exercise electrocardiography does not provide useful information for predicting or preventing events due to cardiovascular disease. Dr. Alpert points out that this is a straw man argument and provides a very handy list of 15 clinical indications for resting or exercise electrocardiogram (ECG) recording.

Over the past 30 years I have ordered hundreds of ECGs and in reviewing that list, I found 6 of the common indications.  Admittedly some of these tests were in suboptimal conditions.  I am thinking primarily of the patient on a psychiatric unit with chest pain. In settings where I have practiced, several factors led to situations where I was getting the ECG and doing the early work before the consultant arrived.  In some rare cases, the troponins were being collected while the patient was still on the psychiatric unit.  In those cases the indication was to rule out acute ischemia pending additional biomarkers. 

If you examine patients, I found it was a common occurrence to makes diagnoses of arrhythmias - that were previously unknown to the patient - most commonly atrial fibrillation.  In some cases, ventricular arrhythmias and rhythms due to conduction disturbance are also noted.  An ECG is a very inexpensive test to determine what is happening. It is also a good way to get consultants interested in the problem.

The advent of concern about the QTc interval in psychopharmacology was probably the biggest driver for psychiatrists to order ECGs.  According to Dr. Alpert this is a legitimate indication for ordering the ECG and the bulk of ECGs I have ordered have been focused on matters of cardiac conduction.  The majority of those orders are based on the characteristics of the medication.  The FDA has made this problem a lot harder than I think it needs to be.  It would be useful to have a screening test for rapidly identifying patients who might be at higher risk for this abnormality but that would probably not take into account anatomical abnormalities that can affect the problem.  There is a certain amount of mystery in this area - when I see medications like haloperidol flagged for QTc prolongation and I have consulted on ICU patients taking haloperidol on telemetry and never seen a case - it tells me that some of this screening and concern may not be that well founded.

I also use the ECG (in addition to the cardiac review of systems) in cases of polypharmacy when the patient is taking multiple QTc prolonging medications.  That may involve a baseline ECG and repeat ECGs over the course of treatment.  On the front end of the evaluation, I often show the patient a drug interaction profile with all of the QTc prolongation flags, discuss the plan with them, and advise them to attend to cardiac symptoms suggestive of rhythm problems.  Even though the USPSTF is usually against screening I have picked up many problems with screening ECGs including QTCs of greater that 510 msec and complete heart block.  I think the problem with characterizing ECGs as screening seem to imply that the patient is asymptomatic and has no cardiac risk factors.  Adding a Bayesian term for the patients psychiatrists see would generally taken them out of that low risk category.  That fact and the low cost of the ECG make this an ideal test for the above problems. 

When I consider the ECG issue and the fact that I have ordered more and more of these tests over the years - I also think back to the 1980s and 1990s when it was not uncommon to see a QTc of 500 msec on a person taking thioridazine.  The Cardiology consultants would ask the high risk threshold question: "Does he really need the medication?"  Any affirmative answer usually resulted in leaving the medication in place.

As psychiatry has evolved, I think that psychiatrists are now in a place where they are (or can be) much more proactive about cardiac conduction problems - both in the initial pharmacological approach and in reacting to ECG abnormalities. The only consistent problem I see is the availability of ECG machines and technicians if the clinic is isolated from medical resources.  It may be impossible to get ECGs when you need them for the above purposes.

If you are a resident or an experienced psychiatrist, I think it will pay to get a copy of Dr. Alpert's editorial and take a look at the list.  I think it is also useful to remember there is screening and there is screening.  While you are at it - consider Cardiology Twitter and follow the Cardiologists there who post ECG tracings, how to read them, and what the clinical findings and treatment was. It is an outstanding learning resource in this skill.

Carefully consider all of the cardiac risk factors affecting the patients that you treat and I am sure you will agree with me - the threshold for obtaining ECGs in patients with severe psychiatric disorders should be low. 



George Dawson, MD, DFAPA


Reference:

1: Alpert JS. Does Resting or Exercise Electrocardiography Assist Clinicians in Preventing Cardiovascular Events in Asymptomatic Adults?. JAMA Cardiol. 2018;3(8):678–679. doi:10.1001/jamacardio.2018.1800.

Does the FDA discriminate against antidepressants?

The FDA came out with a new warning on citalopram on 3/28/2012.  The main point of the warning is that citalopram may lead to electrocardiogram changes that can be associated with an abnormal heart rhythm or arrhythmia that is potentially fatal.  The specific change is prolongation of the QTc interval or the interval that correlates with the total duration of ventricular activation and recovery.

Citalopram is a widely used antidepressant medication and it widely used for three reasons.  It is not likely to have a lot of interactions with other drugs.  Citalopram figured prominently in the STAR*D algorithm from the largest study done on enhancing antidepressant effectiveness.  A third reason is that it is a generic medication and it is very inexpensive.  Psychiatrists have broad experience with the drug and the general experience is that it is well tolerated with little toxicity.

Flecainide is a Type IC antiarrhythmic agent indicated for the prevention of paroxysmal atrial fibrillation (AF), paroxysmal supraventricular tachycardia (PSVT), and the prevention of life-threatening ventricular  arrhythmias like sustained ventricular tachycardia. The FDA warnings on the drug include proarrhytmic effects and excess mortality.  The excess mortality was directly observed in a clinical trial done to suppress ventricular arrhythmias.

The black box warnings for each drug listed below are directly from Medline:

Looking at the safety concerns for both medications - important differences emerge.  First, the FDA recommends maximum doses for the citalopram not just for the a maximum dose for adults but in specific conditions including aging.  Searching the FDA web site shows exactly 25 references for safety concerns of flecainide and none of them contain that level of information.  Second, the citalopram warning shows a table of QTc interval changes by dose for both citalopram and escitalopram.  There is no information in FDA documents (that I could find) for flecainide even though it is widely accepted that flecainide causes dose related changes in not just the QTc interval but also the QRS and PR intervals  along with a host of additional effects on cardiac pacemakers and conduction.  The  overall tone of the release is  that citalopram is a potentially cardiotoxic drug.  Third, the ECG monitoring recommendations are not internally consistent.  The absolute cut off of a QTc interval of 500 ms is highly unlikely - even in cases where the patient is taking 60 mg per day or more of citalopram.  It is also unlikely that the QTc intervals in the citalopram warning will lead to a QTc interval of greater than 500 ms.  This will result in tens of thousands of ECGs done because that is the only way that the QTc interval can be determined.

The black box warnings and the recently issued warning all considered, serious questions are raised relative to drugs with known cardiotoxicity and the whole issue of QTc warnings in all psychiatric drugs.  Certainly nobody wants a rare severe complication as a result of a prescription medication but can it really be avoided?  What good would ECG screening do?  There have not been any trials to address that issue of whether all patients taking citalopram need baseline ECGs.  All the patients taking flecainide have probably had multiple ECGs done that indicate a possible need for treatment but there is little guidance on the ECG issue.  In many patients taking flecainide, patients get serial ECGs and they do exercise stress tests to rule out proarrhythmic effects.  Are the same precautions needed for patients on citalopram?

Are the thresholds for treatment different given the fact that flecainide caused increased mortality during clinical trials and citalopram did not?  There would be an argument that flecainide is used to treat life-threatening arrhythmias, but the other indication is for prevention of atrial fibrillation and atrial fibrillation is not a life threatening arrhythmia.  With regard to the seriousness of the diagnosis, major depression carries a lifetime mortality of 10%.  Finally, where is the table on the relationship between flecainide dose and QTc prolongation like we see for both citalopram and escitalopram?  Is it possible that flecainide has more of an effect throughout the dosage range than citalopram?

These are serious questions given that I have already established that there is a significant bias in the media against psychiatry, psychiatrists and psychiatric medications.  The most recent FDA warning has created a lot of anxiety for psychiatrists and any patient taking citalopram.  The majority of those patients are being seen by primary care physicians.

  

If citalopram is that cardiotoxic, let's see the evidence and let's see how it compares to a medication with known cardiotoxicity.  Let's have the same level of warning for both medications and some concrete ideas about what needs to be done to manage that risk.

George Dawson, MD, DFAPA