Two Newish Antidepressants - What You Need to Know
In 2011, the first new antidepressant in about a decade came on the market, Viibryd (vilazodone), A couple of years later, Brintellix (vortioxetine) made its debut. Both meds work in a manner similar to SSRIs, but have additional mechanisms that may justify placing them in a separate class.
At the 2015 Psychiatric and Mental Health Congress held in San Diego this weekend, I had a chance to attend two separate talks on each of these antidepressants. Be advised: These talks were put on by the drug companies, complete with free lunch. The lunches were delicious. Here is what you need to know …
We are familiar with SSRIs such as Prozac and Paxil. They are believed to work by blocking the “reuptake” of the neurotransmitter serotonin.
Okay, let’s back up. Imagine two neurons side by side, separated by a gap. The gap is the synapse. Call the neuron on the left the presynaptic neuron, the one on the right postsynaptic. When everything is working right, the presynaptic neuron fires serotonin into the synapse.
Serotonin is just one of a class of neurotransmitters - messenger molecules that help link brain cells to each other and join into networks. The serotonin crosses the synapse and docks to receptors on the postsynaptic neuron (plus some on the presynaptic side). Chemicals are released, the message is delivered.
In the next phase of the process, in preparation for the next release, a “transporter” on the presynaptic neuron vacuums up any left-over serotonin. SRRIs work to defeat this process by locking on to the transporter sites, thereby blocking reuptake.
This is sort of like plugging the drain while leaving the water running. More serotonin in circulation results in more receptor dockings, making the target neuron happy.
No doubt, you’ve heard this story many times. What you probably haven’t heard is that the serotonin system is immensely complicated, with no end of potential places where things can go wrong. One of these may occur further upstream when tryptophan is synthesized into serotonin.
So, as one presenter pointed out, if your brain isn’t producing enough serotonin to begin with, there may be precious little serotonin in circulation to give an SSRI something to work with. This is a case, in other words, where the SSRI may not work.
There are some 14 different serotonin receptors, and not all of them have to do with mood. Digestion and sexual function also loom large.
The receptor most relevant to us is the 5HT1A receptor. In the presynaptic neuron, this receptor serves to inhibit the release of serotonin. Postsynaptically, 5HT1A receives serotonin in a way that appears to program the neuron to elevate our mood.
As well as acting as an SSRI, Viibryd and Brintellix act as “agonists” at this receptor. In other words, in this context, the drug mimics serotonin and fits the receptor like a lock into a key.
“Agonists” are fairly common meds. In psychiatry, the novel anxiety med Buspar binds to 5HT1A, as do some of the second-generation antipsychotics, including Abilify.
Viibryd and Brintellix also bind (sometimes partially) to other serotonin receptors. The literature put out by both manufacturers expressly states that the clinical effect of 5HT1A and other binding is unknown. But at the luncheon presentations, the speakers did leave the clear impression that something apparently good does happen.
Perhaps some of the good involves lower sexual side effects and weight gain compared to SSRIs, and possible earlier onset of action. The speakers at both presentations certainly played these up. Agonist action to the rescue? Who knows?
In addition, Brintellix’ manufacturer is trumpeting the drug’s lack of “poop-out” (fairly common in SSRIs), with a 24-month trial to back up its claims. (Most antidepressant clinical trials typically last about eight weeks).
In clinical trials, each drug did about as well in improving depression symptoms as the traditional SSRIs. But this is not the same as saying there is no difference. Clinical trials test for averages. They do not take into account who is more likely to respond to one type of drug vs another.
We can safely assume that many of those who respond to SSRIs will also respond to these newer antidepressants. But there may also be a group of individuals who fare better (or worse) on these new antidepressants. Either way, the Viibryd people don’t want you to wait until after you’ve failed on your SSRI before trying their drug. “Start with Viibryd,” reads their marketing literature to clinicians.
Actually, if antidepressant treatment is the way to go, we trust your clinician will prioritize your needs over those of some drug company’s marketing team. The agonist action of these new drugs suggest we now have a wider choice than before, which is always good. But when all is said and done, finding the antidepressant that works best for you is still a crapshoot.
Make sure your doctor is aware of all your concerns. And once on any antidepressant, stick to his or her instructions (such as when to take the drug) and keep him or her fully informed, especially if you are encountering unexpected side effects.
Be wise, live well …
John is an author and advocate for Mental Health. He wrote for HealthCentral as a patient expert for Depression and Bipolar Disorder.