BLOG: Can you use phenylephrine eye drops in patients taking antidepressants?

Each room in my clinic has a list of medications taped to the wall. It’s basically the only thing on the walls besides the phone number to call during an emergency and the eye chart.

The lists in each room are starting to yellow and rip, and yesterday I thought about replacing them. On the list are all the medications that patients can take in which phenylephrine use is contraindicated. It’s about 15 meds long and essentially lists every monoamine oxidase inhibitor (MAOI) and tricyclic antidepressant (TCA).

We take this potential contraindication seriously at the hospital because a lot of our patients are on these meds and a lot of our patients are elderly with hypertension, and any risk of blood pressure spike could be quite serious. But I also know that a lot of eye doctors do not consider any interactions with phenylephrine and give it to nearly all of their patients when dilating. So I thought I would get into the literature about phenylephrine and antidepressants and see what I could find out.

The concern with patients on certain antidepressants is that phenylephrine could potentiate a spike in blood pressure. The two main categories of antidepressants with contraindications to phenylephrine are MAOIs and tricyclics.

MAOIs were the first type of antidepressant developed, so we’ll start there. The most common MAOIs prescribed in the U.S. are Emsam (selegiline, Mylan), Nardil (phenelzine, Pfizer), Marplan (isocarboxazid, Validus) and Parnate (tranylcypromine, GlaxoSmithKline).

Monoamine oxidase acts to break down neurotransmitters like norepinephrine (and dopamine and serotonin); thus, MAOIs act to increase the amount of these chemicals in our synapses. Norepinephrine is the main neurotransmitter of the sympathetic nervous system and works to immediately increase our blood pressure. Thus, a sympathomimetic like phenylephrine, given in combination with a MAOI, which is also stimulating the sympathetic system, has the potential to elevate blood pressure into a hypertensive crisis.

Incidentally, monoamine oxidase is also involved in other processes in the body, including the breakdown of tyramine, an amino acid involved in blood pressure regulation. Tyramine helps release more norepinephrine. Thus, to prevent hypertensive crises, patients who take MAOIs should stay away from foods rich in tyramine like strong/aged cheeses, cured meats, yeasts, beers and dried fruits.

However, there isn’t a clear consensus on MAOIs and phenylephrine in the literature, and the reason is twofold. First, phenylephrine is a direct-acting sympathomimetic as opposed to an indirect one that uses the tyramine process. Theoretically, a direct-acting sympathomimetic would only work on end-organ receptors and would not have an effect on norepinephrine release. It would also have reduced systemic effect when given topically as an eyedrop. Second, the literature is split as to whether patients on MAOIs actually experience blood pressure elevation when given phenylephrine topically. Some studies show no effect, and some show “three- to sevenfold increase in cardiovascular response.” But these studies are few and with low sample size, as you might imagine it would be difficult for a modern review board to approve patients on a rarely used antidepressant taking a medication that could cause a hypertensive crisis. One frequently cited study involved “four healthy male clinical pharmacologists” who volunteered to take IV phenylephrine while on different types of antidepressants for about a week. Many studies use dogs. Nearly all of them were done in the 1980s or before, when MAOIs were more popular.

In the present day, TCAs are a more popular prescription for depression, but still relatively rare compared to selective serotonin reuptake inhibitors. Thankfully, the mechanism of action of TCAs and phenylephrine is much more simple.

TCAs work to block the reuptake of norepinephrine into presynaptic neurons, thus increasing the sympathomimetic effect. The most common TCAs are Anafranil (clomipramine, Mallinckrodt), Elavil (amitriptyline, Stuart), Pamelor (nortriptyline, Mallinckrodt), Sinequan (doxepin, Pfizer), Surmontil (trimipramine, Teva), Tofranil (imipramine, Mallinckrodt) and Vivactil (protiptylin, Teva), among others.

In truth, there is confusion among clinicians and in the literature about the safety of using phenylephrine with MAOIs and TCAs. Pharmacology textbooks and websites will tell you that topical phenylephrine even at 2.5% concentration is contraindicated in patients on these meds. The phenylephrine package insert I looked at says nothing about these meds being contraindicated. A case report published in 2000 acknowledged the risk of hypertensive crisis, but advised using adrenaline in MAOI patients only “in life-threatening situations” (i.e., anaphylactic reactions).

I think if the general medical community has pause in whether to use sympathomimetics even in life-threatening situations, we as an ocular community should get in the habit of looking for MAOIs and TCAs before using phenylephrine to dilate.

References:

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Heinemann, Elsevier.

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Fenwick MJ, et al. J Accid Emerg Med J. 2000;17:143-144. doi: 10.1136/emj.17.2.143.

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