Developments in the discovery and design of intranasal antidepressants

Expert Opin Drug Discov. 2020 Oct;15(10):1145-1164. doi: 10.1080/17460441.2020.1776697. Epub 2020 Jun 21.


Introduction: Depression remains a major cause of morbidity worldwide; consequently, there is a need in neuropsychiatry for new antidepressants with a rapid onset of action. Intranasal administration of antidepressants is an attractive and promising approach to the treatment of mental disorders, as this route is noninvasive, offers a fast onset of action and improved drug bioavailability, allows a drug dose reduction, as well as gives the possibility to bypass the blood-brain barrier and reduce the number of systemic side effects.

Areas covered: This review is a comprehensive discussion of the available intranasal drugs that have found application as antidepressants. The results of relevant clinical studies are presented. Additionally, the use of nanotechnology-based formulations for enhancing the intranasal delivery of antidepressants is briefly described.

Expert opinion: Intranasal drug delivery has a huge potential for antidepressant administration, but its use in the treatment of central nervous system disorders is currently very limited. The nasal route of antidepressant delivery is noninvasive, improves drug bioavailability, as well as allows to overcome the problem with the blood-brain barrier, gastrointestinal absorption, and first-pass metabolism. In our opinion, fast-acting intranasal antidepressants will be widely used in the treatment of mental disorders in the future.

Keywords: Depression; antidepressant; anxiety; esketamine; intranasal drug delivery; oxytocin.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacokinetics
  • Biological Availability
  • Depression / drug therapy*
  • Drug Delivery Systems
  • Drug Design*
  • Drug Discovery
  • Humans
  • Tissue Distribution


  • Antidepressive Agents