Developments in the discovery and design of intranasal antidepressants

ABSTRACT

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
• anxiety
• antidepressant
• intranasal drug delivery
• esketamine
• oxytocin

Article highlights

• Intranasal antidepressants are attractive and promising therapeutic options in mental disorders because it is noninvasive, fast-acting, improves drug bioavailability and overcomes the problem of the blood-brain barrier as well as gastrointestinal absorption, and first-pass metabolism.

• The way a drug is transported from the nasal cavity to the brain (via olfactory pathways or the trigeminal nerve pathway), low drug bioavailability, the occurrence of enzymatic barrier, mucociliary clearance, protective barriers and the used drug delivery device all have an impact on the effectiveness of nasal antidepressants.

• Intranasal esketamine is the only approved drug by the FDA for treating TRD in adults, based on positive results of phase III RCT. Intranasal oxytocin, insulin and PH94B are other drugs with antidepressant potential which have been investigated during clinical trials.

• Nanocarriers, triggerable systems, and macromolecules have the potential to enhance intranasal antidepressant delivery. These systems are currently being studied in preclinical trials.

• Intranasal drug delivery has a huge potential for antidepressant administration, but further research is necessary to deepen our knowledge in the field of optimization of the intranasal delivery route, better understand the exact mechanism of intranasal antidepressant action and dosing and safety issues.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by the Statutory Funds of the Maj Institute of Pharmacology of the Polish Academy of Sciences.