New-generation, non-SSRI antidepressants: Drug-drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others

Med Res Rev. 2020 Sep;40(5):1794-1832. doi: 10.1002/med.21671. Epub 2020 Apr 13.


After the development of "classical" tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market. The selective serotonin reuptake inhibitor class is the best-known one, but many others exist, usually identified by their mechanism of activity. In this second part of the review, focused on new-generation antidepressants not included among selective serotonin reuptake inhibitors, the following classes are considered: noradrenergic and selective serotonergic antidepressants; norepinephrine reuptake inhibitors; serotonin, norepinephrine and dopamine reuptake inhibitors; melatonergic agonists and selective serotonergic antagonists; norepinephrine and dopamine reuptake inhibitors; and so forth. These different mechanisms underlie tolerability and safety profiles that can be very different among the classes, with each one providing significant advantages and disadvantages in comparison with others. The main characteristics of the following antidepressants are described: mianserin, mirtazapine, setiptiline, reboxetine, viloxazine, teniloxazine, atomoxetine, nefazodone, agomelatine, bupropion, esketamine, and tianeptine. The paper is focused on their metabolism and interactions, but also includes brief notes on analytical methods useful for their therapeutic drug monitoring.

Keywords: drug-drug interactions; metabolism; metabolites; new-generation antidepressants (NGAs); therapeutic drug monitoring (TDM).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents
  • Drug Interactions
  • Drug Monitoring
  • Humans
  • Pharmaceutical Preparations*
  • Serotonin Uptake Inhibitors*


  • Antidepressive Agents
  • Pharmaceutical Preparations
  • Serotonin Uptake Inhibitors