SUMMARY  

• SPRAVATO is intended for administration by the patient under the direct supervision of a healthcare professional, using 2 devices (for a 56 mg dose) or 3 devices (for an 84 mg dose), with a 5-minute rest between use of each device.¹
• Doses greater than 84 mg have not been systematically studied in patients with depression. The clinical trial program for treatment-resistant depression included safety data for 2,283 subjects who received at least 1 dose across completed phase 1, phase 2, and phase 3 studies. Two completed phase 1 studies in healthy volunteers included subjects that received doses higher than the maximum prescribed dose of 84 mg. The maximum dose tested in those 2 studies was 112 mg.²
  • In one phase 1 study (14 subjects), the incidence of treatment-emergent adverse events (TEAEs) having at least 3 reported events in the esketamine (ESK) 112 mg group was >2 times higher than in the ESK 84 mg group for dizziness postural, head discomfort, feeling hot, and hyperhidrosis.²
  • In another phase 1, single-dose, double-blind, crossover study in recreational drug users, patients were randomized to placebo nasal spray (and IV placebo), ESK 84 mg (and IV placebo), ESK 112 mg (and IV placebo), or IV ketamine 0.5 mg/kg (and placebo nasal spray).^1-3
    • The incidence of the following TEAEs reported in at least 3 subjects were >2 times higher in the ESK 112 mg group compared to the ESK 84 mg group: dizziness and nasal congestion.² This study also showed that the 112 mg group experienced much higher scores for “hallucinating”, “floating”, “detached”, and “spaced out” measures than in the 84 group at 1 hour postdose.¹
    • The pharmacokinetic profile after administration is illustrated in Figure: Mean (SD) Plasma Concentration-Time Curves After Intranasal Administration of ESK 84 mg and 112 mg and IV Ketamine 0.5 mg/kg.³

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 14 April 2024.