The Two Newest Antidepressants: How Do They Stack Up? | Pharmatherapist (2024)

Trintellix (vortioxetine)

If you’re a TV watcher, you’ve probably seen a flurry of recent advertisem*nts for Trintellix lately. The ad describes and illustrates depression as a “tangle” of multiple symptoms, which presumably Trintellix will somehow untangle. Also if the generic name vortioxetine rings a bell with you, it’s because Trintellix formerly went by the brand name Brintellix. The brand name change from Brintellix to Trintellix came about to avoid prescribing and dispensing errors related to confusing Brintellix with the blood thinner Brilinta.

Trintellix is considered a multimodal antidepressant in that it not only operates as an SSRI, but also affects multiple other serotonin receptors. The approved dose is 10-20mg per day. Side effects are similar to other SSRIs.

In an effort to get a leg up on competitors, the manufacturer conducted studies in an attempt to demonstrate that Trintellix improves patient performance on cognitive tasks, making it a “smart”antidepressant so to speak. But these were denied by the FDA. I can only conclude that the FDA’s skepticism hinged on the belief that Trintellix is no better than other antidepressants for improving cognition in depression and thus has no direct pro-cognitive benefit worthy of an expanded FDA indication.

I’m skeptical too.

Fetzima ( levomilnacipran)

Fetzima is actually an SNRI (serotonin and norepinephrine reuptake inhibitor), putting it in the same class as Effexor XR, Cymbalta and Pristiq. However, Fetzima is more selective for blocking norepinephrine than these others — as much as a 15-fold greater selectivity for norepinephrine than for serotonin.

But does enhanced norepinephrine selectivity mean anything clinically? Some researchers have gone so far as to implicate that there is a distinct “norepinephrine deficiency” depression — associated with poor concentration, low physical drive, inattentiveness, and cognitive impairment which is distinct from a “serotonin deficiency” depression — associated with high levels of distress, appetite disturbances and suicidality.

It would be quite the find if we could identify depressive subtypes that respond to specific antidepressants; but clinically, psychiatric medicine isn’t anywhere close to that, so evidence for a “norepinephrine deficiency” depression is quite the stretch. Nevertheless, this hasn’t stopped the company drug representatives from promoting Fetzima as possessing special norepinephrine super powers. The company hasn’t compared this drug with anything more robust than placebo, and interestingly, one of the 10-week placebo studies didn’t support Fetizma as being better at any particular neurotransmitter profile of symptoms. Instead, it improved only the same types of symptoms targeted by other antidepressants.

A couple of months ago in this space, I wrote about some of the peripheral benefits of antidepressants to users –such as helping everyday life go smoother, feeling brighter and improved outlook. Many, many of you contacted me in support of this newfound position. Trintellix and Fetzima no doubt are quite capable of providing these same benefits and even more for their users.

These two medications though have taken matters a step further. Both have made claims regarding improved cognitive performance linked to clinical depression, and in neither case is there reliable data to support such claims. None of this has stopped drug reps from transmitting this uncorroborated information to physicians eager to write a prescription because the drug is new and just might be the right answer for getting a patient over the depression hump.

Some manifestation of vulnerability always accompanies depression, so if some patients are being fed claims that are untrue, this is fodder for false hope for those looking for relief from the next new pill. Which is a shame.

Building a better antidepressant mousetrap has been quite the challenge for science. To date, no antidepressant consistently outperforms Prozac over time. And, it is 28 years old.

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Attribution Statement:
Joe Wegmann is a licensed pharmacist & clinical social worker has presented psychopharmacology seminars to over 10,000 healthcare professionals in 46 states, and maintains an active psychotherapy practice specializing in the treatment of depression and anxiety. He is the author of Psychopharmacology: Straight Talk on Mental Health Medications, published by PESI, Inc.

To learn more about Joe’s programs, visit the Programs section of this website or contribute a question for Joe to answer in a future article: joe@thepharmatherapist.com.