The More Things Change…

For sure, you know the backend of this common proverb.

new_pillsI invoke this old saying with regard to the two newest antidepressants on the U.S. drug market – Fetzima® (levomilnacipran) and Brintellix® (vortioxetine). Let’s take a look at them:


Fetzima is a serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant. Others in this category that you probably recognize are Effexor, Cymbalta and Pristiq. The efficacy of Fetzima at once-daily doses of 40-120mg was established in three randomized, placebo-controlled studies in adults with major depressive disorder (MDD).

Fetzima is an isomer, or more simply a clone of the SNRI Savella® – which is approved for the treatment of fibromyalgia. Although their molecular structures are similar, Fetzima is not approved for fibromyalgia and Savella is not approved for depression. Go figure. The Fetzima-Savella relationship is similar to that of Celexa-Lexapro, although Celexa and Lexapro are both selective serotonin reuptake inhibitors (SSRIs).

As for the side effects of Fetzima, round up the usual suspects: nausea, tachycardia, palpitations, sexual dysfunction and weight gain.


Like the SSRIs you’re familiar with (Prozac, Zoloft, Lexapro, etc.) Brintellix is a serotonin reuptake inhibitor. It’s also an “agonist,” an activator so to speak of a specific serotonin receptor subtype – the 5HT1A receptor. The anti-anxiety agent Buspar, the antipsychotic Abilify and the antidepressant Viibryd are also activators of this particular receptor. None of these drugs have distinguished themselves remarkably for depression – whether used as monotherapy or as augmenting agents – in spite of this so-called “novel” twist exerted on serotonin. This is because receptor-binding capabilities are often overrated and denote advantages that are mostly theoretical in nature. A drug’s chemistry cannot be counted on to provide the intended effect.

Brintellix’s approval is based on the usual placebo studies which revealed that its effective dosage range is from 5-20mg daily. As for side effects, nausea was the most commonly reported, while weight gain was negligible – a plus well worth mentioning. (The same appears to be true of Viibryd).

Therapeutically, Brintellix is another player on the “me too” antidepressant stage. And of course, its price tag – and that of Fetzima discussed above – is top drawer.

Antidepressants have three strikes against them:

  1. They suffer from sameness.
  2. Their slowness stretches the patience of the already vulnerable user.
  3. People take them too long, develop tolerance and underestimate the difficulty of withdrawal.

With the “chemical imbalance” theory all but debunked and the mysteries of the limbic system still looming large, neuroscience, and subsequently the drug manufacturers, are left with cloning, modifying and copying existing medications. And all the while, saturation drug marketing is alive and well selling slogans like “simple pleasures shouldn’t hurt” and depicting people happily dancing in lily fields purportedly via antidepressant use.

Depression is far too complex for a pill to solve – jump-start yes, but solve, no.

Users are best served by gaining clarity on specifically what they want the antidepressant to do, and more importantly, for how long.

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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.

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