Dr. Cook: The past five decades have been an era where the monoamine neurotransmitters have really dominated the trends in psychopharmacology. The triad of norepinephrine, serotonin, and dopamine has been the primary foundation both for new drug development and for our conceptual models about psychiatric illnesses, as well as treatment.
When the SSRI [selective serotonin reuptake inhibitor] agents were introduced, there was traction for the idea that we could have agents that affected a single neurotransmitter system more or less purely, instead of, for example, the way that the tricyclic antidepressants had binding to targets in all three systems. As we ran historically through the SSRIs, there was a tendency for the selectivity to become greater and greater by design, with an even greater affinity for the serotonin reuptake transporter, and even less affinity for other targets.
In parallel with this, the idea of the dual-action reuptake inhibitors [serotonin-norepinephrine reuptake inhibitors (SNRI)] was marked by the introduction of products such as venlafaxine, duloxetine, and now desvenlafaxine, or products that had affinity at receptors as well as at the reuptake pumps, like vilazodone. A new dual reuptake SNRI agent, levomilnacipran, was approved by the US FDA in July of this year. Here the published data show efficacy greater than placebo, but how that compares with other agents is a question where we are still eagerly awaiting more data from clinical trials.1,2
Narrator: Similarly, another new antidepressant, vortioxetine, was also recently approved by the FDA.3 The approval was based on safety and efficacy data from six multicenter, randomized,
Dr. Cook: Newer compounds in the development pipeline include the triple reuptake inhibitors (TRIs) or other variations on that reuptake inhibition theme, as ways to alter neurotransmission to the synapse, or agents with affinity for dopaminergic targets.
Narrator: Amitifadine (EB-1010) is an example of a TRI currently undergoing
Dr. Cook: The field is, of course, eagerly awaiting the publication and presentation of those results.