Of possible interest to diver's taking Celexa (citalopram) or another SSRI.+

[DocVikingo]

[NOTE: Torsade de Pointes (TdP) is a form of ventricular tachycardia (rapid heart rate) in which the electrical pulse in the heart undergoes a cyclical variation in strength, giving a characteristic electrocardiogram (ECG) resembling a twisted fringe of spikes.]

Citalopram-Induced Long QT Syndrome and the Mammalian Dive Reflex

Regards,

DocVikingo

 

[RyanT]

Thanks, Doc!

 

[Duke Dive Medicine]

That's a fascinating case. We had a similar one a while back where the diver had been taking prescribed fluoxetine, then took diphenhydramine for allergies and dimenhydrinate (which gets metabolized to diphenhydramine) for motion sickness. The diver went unresponsive at the safety stop, was pulseless on the boat, had CPR done by a physician who happened to be on board, achieved ROSC, then got evacuated to us by the Coast Guard. The story we got was "we are bringing you a diver with a gas embolism who is s/p cardiac arrest". Diver was awake, alert, oriented, pleasant, and complaining of a sore chest on exam in the ED. Neuro was normal with the exception that we didn't assess gait. 12-lead showed prolonged QT interval. D/C'd the Prozac and advised the diver to use caution when combining the other two meds, which can also cause QT prolongation. The addition of the diving reflex is interesting and thought-provoking. Thank you DocV!

Best regards,
DDM

 

[drrich2]

Thanks indeed for posting; interesting case. And worth clicking through to read the full article; there's a lot more to it than 'Gee, looks like Celexa killed somebody.' Quite a number of medications can prolong QTc intervals to some extent, and some people have a naturally long one.

That's an unusually high dose of celexa, plus there's mention of the patient having been on 2 potentially hepatotoxic drugs (wonder what?), which could've reduced ability to clear the drug.

Any idea just how signicant the mammalian dive reflex is thought to be on QTc interval concerns?

12-lead showed prolonged QT interval.

Do you remember just how prolonged it was?

Richard.

 

[uncfnp]

That does seem like a high dose. At the urgent care we avoid adding, even temporarily, any drug with an additive effect on QT if the patient is on 40 mg.

Had no idea the dive reflex could trigger a prolonded QT event. Yet another thing for PCP's to keep in mind when juggling health needs, prescriptions and interactions. And another instance when the diver may need to be proactive in educating their provider.

 

[DocVikingo]

Very interesting, DDM -- thanks. When I read this article I thought, "Geez, I'll bet hardly any diving medical professionals have ever seen or even heard of a case like this."

It is worth noting that the reported post-mortem blood level of citalopram of 1300 ng/ mL is mind-bogglingly high and far within the toxic range. Given that steady-state serum concentrations associated with optimal response to citalopram are in the range of 100 to 250 ng/mL, in this case one would strongly expect to observe significant fatigue, insomnia, blurry vision/dilated pupils, confusion/delirium, dry mouth, increased body temperature, flushed face & or other anticholinergic effects. Makes one wonder how these went unnoticed/unaddressed.

While regular blood level monitoring is not indicated in most cases, serum citalopram level can be assessed with a lab assay known as the CITAL (CITAL - Clinical: Citalopram, Serum). Indeed in divers on an SSRI who have risk factors such as concurrent treatment with potentially hepatotoxic agents, concurrent treatment with other drugs associated with extended QT intervals (e.g., certain antiarrhythmics, antipsychotics, tricyclic antidepressants, antimicrobials, antihistamines, antiretrovirals), a known prolonged QT interval/abnormality of cardiac rhythm, or with signs/symptoms of congestive HF, periodic assessment of citalopram serum blood level and ECG might be prudent.

Regards,

DocV

This is educational only and does not constitute or imply a doctor-patient relationship. It is not medical advice to you or any other individual and should not be construed as such.

 

[DocVikingo]

That does seem like a high dose. At the urgent care we avoid adding, even temporarily, any drug with an additive effect on QT if the patient is on 40 mg.

Hi uncfnp,

As the above article notes, the FDA did issue a Drug Alert in August of 2011. However, an extremely large scale study (>600,000 VAH subjects) published in the June 2013 issue of the American Journal of Psychiatry reported that, when compared with daily doses ranging between 1 and 20 mg, doses greater than 40 mg of citalopram were actually linked to a lower risk for ventricular arrhythmia and all-cause and noncardiac mortality. The research concluded that, "These findings raise questions regarding the continued merit of the August 2011 FDA warning and provide support for the question of whether the warning itself will cause more harm than good."

Nevertheless, the generally recommended starting citalopram dose is 20 mg qd, with a max recommended dose is 40 mg qd. While dosing largely is a clinical call by the treating doctor, doses >40 mg do appear to me to be unwise in those over age 60 and in those with risk factors such as discussed in my post immediately above. It certainly appears prudent within the urgent care context to "...avoid adding, even temporarily, any drug with an additive effect on QT if the patient is on 40 mg."

Regards,

DocV

 

[DocVikingo]

...there's mention of the patient having been on 2 potentially hepatotoxic drugs (wonder what?), which could've reduced ability to clear the drug.

Hey Richard,

At the time of death, she was taking divalproex (Depakote), 1000 mg per day (generally max recommended daily dose for migraine), and was taking meloxicam (Mobic), 15 mg per day (generally max recommended daily dose), up until shortly before her death, both apparently for migraine and both of which can be hard on the liver, especially at higher doses over extended periods of time (she had been on divalproex for about 2 yrs and had been on meloxicam since prior to that). And, citalopram has, albeit infrequently, itself been associated with liver damage.

Regards,

DocV

 

[uncfnp]

Hi uncfnp,

As the above article notes, the FDA did issue a Drug Alert in August of 2011. However, an extremely large scale study (>600,000 VAH subjects) published in the June 2013 issue of the American Journal of Psychiatry reported that, when compared with daily doses ranging between 1 and 20 mg, doses greater than 40 mg of citalopram were actually linked to a lower risk for ventricular arrhythmia and all-cause and noncardiac mortality. The research concluded that, "These findings raise questions regarding the continued merit of the August 2011 FDA warning and provide support for the question of whether the warning itself will cause more harm than good."

Nevertheless, the generally recommended starting citalopram dose is 20 mg qd, with a max recommended dose is 40 mg qd. While dosing largely is a clinical call by the treating doctor, doses >40 mg do appear to me to be unwise in those over age 60 and in those with risk factors such as discussed in my post immediately above. It certainly is prudent within the urgent care context to "...avoid adding, even temporarily, any drug with an additive effect on QT if the patient is on 40 mg."

Regards,

DocV

Hi DocVikingo and thanks for the info on the additional study. I read the Abstract but admit I didn't read the study itself. The results seem counterintuitive and contradict the information from the first post which stated, if I read and remember it correctly, that the QTc prolongation is dose dependent.

 

[DocVikingo]

Any idea just how signicant the mammalian dive reflex is thought to be on QTc interval concerns?

Not surprisingly, there has not been much research specific to the effect of the mammalian dive reflex (of which the 1st response is bradycardia) on QTc. However, a couple of small but seemingly decent studies suggest that only a limited amount of QT variability is correlated with heart rate in participants who were subject to conditions designed to precipitate the mammalian diving reflex (e.g., immersion of the face in cold water).

Still, this effect, when combined with factors such as an extremely high serum concentration of a drug known to be associated with QT interval prolongation, may have been enough to break the heart's back.

Regards,

DocV