New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs

Curr Med Chem. 2018;25(7):772-792. doi: 10.2174/0929867324666170712165042.


Background: New-generation antidepressants (NGAs) are the latest additions to the clinician's arsenal in the fight against depression. After the introduction of selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups followed, identified by their main mechanisms of activity: serotonin and norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators (SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and selective serotonergic antidepressants (NaSSA); norepinephrine reuptake inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors (SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists (MaSA). Although SSRIs are still the most widely used and well known NGAs, the other groups are increasingly being used in the current therapeutic settings obtaining comparable clinical results, and with tolerability and safety profiles that can often provide significant advantages over those of SSRIs.

Methods: Scopus and PubMed databases were searched for the most significant papers centered on the medicinal chemistry, pharmacodynamics, pharmacokinetics and analysis in human biological fluids of the following antidepressants: venlafaxine, duloxetine, milnacipran, trazodone, vortioxetine, vilazodone.

Results: The main characteristics of commercially available non-SSRI NGAs (belonging to the SNRI, SARI and SMS classes) are described, focusing on the role of analytical methods that can be applied to perform therapeutic drug monitoring (TDM), but also including drug pharmacokinetics, metabolism and interactions.

Keywords: Analysis; chemical-clinical correlations; drug-drug interactions; metabolism; new-generation antidepressants (NGAs); pharmacological properties; therapeutic drug monitoring (TDM)..

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / metabolism
  • Antidepressive Agents / pharmacokinetics
  • Antidepressive Agents / therapeutic use*
  • Depression / drug therapy*
  • Depression / metabolism
  • Drug Monitoring*
  • Humans
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / metabolism
  • Serotonin Uptake Inhibitors / pharmacokinetics
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Serotonin and Noradrenaline Reuptake Inhibitors / metabolism
  • Serotonin and Noradrenaline Reuptake Inhibitors / pharmacokinetics
  • Serotonin and Noradrenaline Reuptake Inhibitors / therapeutic use*


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Serotonin