Esketamine ($ Spravato)

Dissociative (glutamate NMDA antagonist; opioid μ/κ agonist; dopamine D2 agonist; inhibits dopamine/serotonin/norepinephrine reuptake)

Dosing

Defer to treatment team on dosing. Generally the dose is tapered down in frequency after 4 weeks and

IV Ketamine is more effective but not FDA-approved (so costs more). Esketamine is less effective.

Avoid clinics that offer unsupervised, at-home ketamine. Ketamine is poorly absorbed so oral or IM dosing unlikely to work.

Management

Works rapidly, so ideal for severe depression (such as to avoid hospitalization). However, unlikely to work beyond 4 weeks. Can “jump start” TMS (start with esketamine, then switch to TMS after 2-4 weeks).

Although esketamine is FDA approved for depression with suicidality, it does not actually reduce suicidality (the approval is based on safety in that population).

RISKS: Transient hypertension, dissociation, hallucinations. Problems with converting to recreational use. Ketamine is used as the human model for schizophrenia and can cause psychosis.

EMR Text