September 2018

NEWS & OPINION

Chief medical editor’s corner of the world
Flomax has a big brother, and the psychiatrists have him


by Jack Parker, MD, PhD, and Christina Pierpaoli Parker, MA

Intraoperative floppy iris syndrome (IFIS) is one of the most common causes of pupillary constriction during cataract surgery and is associated with an increased risk of intraoperative complications. The syndrome was first described by Chang and Campbell in the Journal of Cataract and Refractive Surgery in 2005 and was originally associated with the systemic use of tamsulosin. Subsequently, IFIS has been associated with other alpha-1 adrenergic receptor antagonists and the homeopathic saw palmetto. The association of IFIS with the use of prazosin for the treatment of post-traumatic stress disorder adds a new risk factor that ophthalmologists should be aware of.

Eric Donnenfeld, MD,
chief medical editor


Earlier this year, a bombshell study hit the pages of the New England Journal of Medicine—a multicenter, randomized, double-blind, placebo-controlled trial demonstrating prazosin’s ineffectiveness to treat post-traumatic stress disorder (PTSD) in a sample of military veterans.1
That report ignited a firestorm of controversy, with physicians and psychologists alike jumping into the fray to debate, including in pages of some popular outlets like Scientific American.2–4
But for us, the report provoked a different reaction—a bizarre sense of confusion. Prazosin, the weak anti-hypertensive medication, is being prescribed for PTSD? Apparently, yes. Since at least the year 2000, the U.S. Department of Veterans Affairs (VA) has used this alpha-1 adrenergic blocking agent to treat trauma-induced nightmares, in some cases as first-line medical therapy.5,6 The medication suppresses noradrenaline’s nighttime access to the brain, thereby protecting rapid eye movement (i.e., dreaming) sleep from unwanted activation.5,6
As plausible as that sounds, the published successes with prazosin have frequently involved eyebrow- raisingly high dosages—sometimes up to 45 mg daily.7,8 Compare this to the daily indicated dosage for a “cousin” alpha-1 blocker, Flomax (tamsulosin, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut), which is conventionally recommended at 0.4 mg daily.
This brings us to the punchline: There seems to be a hidden population of psychiatric patients being prescribed a suspect IFIS-producing drug at up to 100 times the standard Flomax dosage. We had no idea.
Does that mean that there’s a group of “super Flomax” users out there? We don’t know. Almost the whole of the literature links IFIS with tamsulosin, specifically, despite the common mechanism of action,9 and there’s only one publication implicating prazosin by name.10 Further, IFIS severity appears at least partially correlated with duration of medication use, and conceivably, patients using prazosin as a psychiatric adjunct may receive abbreviated courses compared to patients being treated chronically for prostatic hyperplasia.11
Even so, it would no doubt be interesting to read reports from cataract surgery in this cohort of patients (and considering the psychiatric prescribing practices of the past 2 decades, ample opportunity to conduct such a study might be found). There is at least some (if less than ideal) awareness of the ophthalmic consequences of tamsulosin among urologists,12 and it might be useful if study data were available to provide psychiatrists and sleep medicine doctors with a similar suggestion for caution.
Even without such evidenced- based recommendations, cataract surgeons may be tempted to breathe a sigh of relief that a potential IFIS-inducer has been publicly exposed. But not so fast—that controversial paper specifically admits that prazosin may still be useful as a sleep aid and nightmare suppressant, at least for a subset of patients. In fact, in an interview, the first author stated bluntly about his study: “I don’t think it should change clinical practice—there are six positive studies and one negative study.” 3,4
As a result, cataract surgeons may be forewarned (decades late, better than never) in operating on patients with a history of PTSD, especially if they are veterans. Their sleep medicine might be the stuff of your nightmares.

References

1. Raskind MA, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378:507–517.
2. Ressler KJ. Alpha-adrenergic receptors in PTSD – failure or time for precision medicine? N Engl J Med. 2018;378:575–576.
3. Joseph A. A drug widely used to treat PTSD symptoms has failed a rigorous trial. Scientific American. February 2018.
4. Joseph A. This drug has been used to treat PTSD symptoms. What happens when it fails a trial? STAT. February 2018.
5. Hendrickson RC, et al. Evidence for altered brain reactivity to norepinephrine in veterans with a history of traumatic stress. Neurobiol Stress. 2018;8:103–111.
6. Onton JA, et al. In-home sleep recordings in military veterans with posttraumatic stress disorder reveal less REM and deep sleep <1 Hz. Front Hum Neurosci. 2018;12:196.
7. Koola MM, et al. High-dose prazosin for the treatment of post-traumatic stress disorder. Ther Adv Psychopharmacol. 2014;4:43–7.
8. Abrams TE, et al. Geographical diffusion of prazosin across Veterans Health Administration: examination of regional variation in daily dosing and quality indicators among veterans with posttraumatic stress disorder. J Rehabil Res Dev. 2015;52:619–27.
9. Chatziralli IP, Sergentanis TN. Risk factors for intraoperative floppy iris syndrome: a meta-analysis. Ophthalmology. 2011;118:730–5.
10. Issa SA, et al. Alpha antagonists and intraoperative floppy iris syndrome: a spectrum. Clin Ophthalmol. 2008;2:735–41.
11. Lunacek A, et al. Ten years of intraoperative floppy iris syndrome in the era of alpha-blockers. Cent European J Urol. 2018;71:98–104.
12. Zhang Y, et al. Assessment of urologists’ knowledge of intraoperative floppy iris syndrome. Urology. 2016;97:40–45.

Editors’ note: Dr. Parker is affiliated with Parker Cornea, Birmingham, Alabama, and the Netherlands Institute for Innovative Ocular Surgery. Ms. Pierpaoli Parker, PhD candidate of clinical psychology, studies at the University of Alabama, Tuscaloosa. They have no financial interests related to this article.

Contact information

Parker
: jack.parker@gmail.com

Flomax has a big brother, and the psychiatrists have him Flomax has a big brother, and the psychiatrists have him
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