Reuptake Inhibitors: SSRIs, SNRIs, and NDRIs

Some of the most commonly prescribed antidepressants are called reuptake inhibitors. What’s reuptake? It’s the process in which neurotransmitters are naturally reabsorbed back into nerve cells in the brain after they are released to send messages between nerve cells. A reuptake inhibitor prevents this from happening. Instead of getting reabsorbed, the neurotransmitter stays — at least temporarily — in the gap between the nerves, called the synapse.

What’s the benefit? The basic theory goes like this: keeping levels of the neurotransmitters higher could improve communication between the nerve cells — and that can strengthen circuits in the brain which regulate mood.

Different kinds of reuptake inhibitors target different neurotransmitters. There are three types:

• Selective serotonin reuptake inhibitors (SSRIs) are some of the most commonly prescribed antidepressants available. They include citalopram (Celexa),  escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil), Prozac, and sertraline (Zoloft). Another drug, olanzapine (Symbyax), is approved by the FDA specifically for treatment-resistant depression. It’s a combination of the SSRI antidepressant fluoxetine (Prozac) and another drug approved for bipolar disorder and schizophrenia called olanzapine (Zyprexa). Aripiprazole (Abilify), quetiapine (Seroquel), and brexpiprazole (Rexulti) have been FDA approved as add-on therapy to antidepressants for depression. Plus, doctors often use other drugs in combination for treatment-resistant depression. Also, the drugs vilazodone (Viibryd) and vortioxetine (Trintellix – formerly called Brintellix) are among the newest antidepressants that affect serotonin. Both drugs affect the serotonin transporter (like an SSRI) but also affect other serotonin receptors to relieve major depression.
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) are among the newer types of antidepressant. As the name implies, they block the reuptake of both serotonin and norepinephrine. They include duloxetine (Cymbalta), venlafaxine (Effexor), desvenlafaxine ER (Khedezla), levomilnacipran (Fetzima), and desvenlafaxine (Pristiq).
• Norepinephrine and dopamine reuptake inhibitors (NDRIs) are another class of reuptake inhibitors, but they’re represented by only one drug: bupropion (Wellbutrin). It affects the reuptake of norepinephrine and dopamine.

Other Antidepressants: Tetracyclics and SARIs

• Tetracyclics are another class of antidepressant with drugs such as asamoxapine (Asendin), maprotiline (Ludiomil), and mirtazapine (Remeron). Although it affects neurotransmitters, Remeron doesn’t prevent reuptake in the same way. Instead, it seems to stop neurotransmitters from binding with specific receptors on the nerves. Because the norepinephrine and serotonin don’t bind to the receptors, they seem to build up in the areas between the nerve cells. As a result, the neurotransmitter levels rise.
• Serotonin antagonist and reuptake inhibitor (SARIs) appear to act in two ways. They prevent the reuptake of serotonin. But they also prevent serotonin particles that are released in a synapse from binding at certain undesired receptors and redirect them instead to other receptors that can help nerve cells within mood circuits function better. Examples include nefazodone (Serzone) and trazodone.