When do you refer a patient with difficult-to-treat depression for esketamine nasal spray versus IV ketamine treatment?  

For treatment-resistant depression (TRD), intravenous ketamine is slightly more efficacious than intranasal esketamine (Spravato), probably due to more controlled bioavailability (all the substance administered is absorbed) and better personalization of doses. However, IV ketamine is usually not cov...

My practice is not set up for ketamine. When a patient has treatment-refractory depression, meaning failure to respond to multiple oral agents, including combinations, I would then entertain other modalities.

There are several considerations here worth discussing. First of all, only esketamine is FDA-approved and covered by insurance - only for severe MDD. IV ketamine is usually out of pocket but it offers more versatility, being less tightly regulated compared to esketamine. It can be used for some othe...