Nasal Sprays – The newest way to address your mental health

The other day I learned about Spravato. Spravato is a nasal spray intended for treatment resistant depression (TRD) and major depressive disorder (MDD). The chemical name for Spravato is eskatemine. Eskatemine is the active enantiomer (S-) of ketamine and is more potent than the racemic mixture. A racemic mixture refers to both S-ketamine and R-ketamine occurring naturally together. S- and R- ketamine are mirror images of each other. In my experience, it is more difficult to synthesize or isolate one specific enantiomer than it is to synthesize the racemic mixture.

Ketamine is known to produce rapid and long-lasting effects treating a variety of mental health disorders including depression, anxiety, and PTSD. The creation of a nasal spray version of ketamine is particularly interesting because it is a way to get the drug into the bloodstream and up to the brain faster than taking it orally and having to go through digestion and metabolism. Taken orally, ketamine reaches the bloodstream approximately 40 min following dosing. Taken as a nasal spray, the peak concentration in the bloodstream is only about 20 minutes. When one is in a mental health crisis, that 20 minutes matters.

Reading about all of this made me think. Why aren’t there more drugs available as nasal sprays? To me, it would provide a new line of options for treatment in a mental health crisis where hospitalization and IV drugs are not available. So I went down a rabbit hole trying to determine if traditionally prescribed medications could be transformed into effective nasal sprays.

When I googled “most commonly prescribed anti-anxiety drug”, the result, according to definitivehc.com, is gabapentin. Gabapentin is a traditionally prescribed for seizures but can also be used to treat anxiety and nerve pain. Interestingly, gabapentin does not change during metabolism. The same molecule that is present in the pill prior to being taken is the same molecule that is present in the bloodstream. This means that, in theory, gabapentin could be made into a nasal spray. This may not be true for a lot of other drugs though.

Nasal spray mental health treatments were never a thing that I considered. But now understanding more of the principles behind how nasal sprays work and the potential advantages, I want to see if this is a therapeutic pathway that is explored more.

Sources

https://go.drugbank.com/drugs/DB11823. Eskatmine.

Hess EM, Riggs LM, Michaelides M, Gould TD. Mechanisms of ketamine and its metabolites as antidepressants. Biochem Pharmacol. 2022 Mar;197:114892.

Culp C , Kim HK , Abdi S. Ketamine Use for Cancer and Chronic Pain Management. Frontiers in Pharmacology. 2020 (11)

Perucca E. The clinical pharmacokinetics of the new antiepileptic drugs. Epilepsia. 1999;40 Suppl 9:S7-13.