Spravato Starting Dose Selection
For adults under 65 years, start with 56 mg; for adults 65 years and older, start with 28 mg. 1
Age-Based Dosing Algorithm
The starting dose of esketamine nasal spray is determined primarily by patient age:
Adults < 65 years:
- Starting dose: 56 mg 1, 2
- This is the standard initial dose for younger adults
- Can be escalated to 84 mg in subsequent sessions based on response and tolerability
Adults ≥ 65 years:
- Starting dose: 28 mg 1, 2
- Lower starting dose accounts for age-related pharmacokinetic changes
- Can be titrated up to 56 mg or 84 mg in subsequent sessions if needed and tolerated
Dose Escalation Strategy
After the initial dose, subsequent dosing follows this pattern 1, 2:
- Weeks 1-4: Twice weekly dosing (56 mg or 84 mg for <65 years; 28 mg, 56 mg, or 84 mg for ≥65 years)
- Weeks 5-8: Once weekly dosing
- Week 9 onward: Once weekly or once every 2 weeks based on response
The dose can be adjusted upward (from 56 mg to 84 mg, or from 28 mg to 56 mg or 84 mg) based on individual response and tolerability during the induction phase.
Evidence for Dose-Response Relationship
Higher doses (56-84 mg) demonstrate superior efficacy compared to 28 mg 3, 4. Meta-analyses show that esketamine doses of 56-84 mg are more effective than 28 mg for reducing depressive symptoms, with the best response found between 56 and 84 mg 3. However, adverse events are strongly dose-dependent, with the high-dose group (≥56 mg) showing greater risk of nausea (RR 3.72 vs 1.69) and dissociation (RR 10.65 vs 3.27) compared to low-dose (≤28 mg) 5.
Important Caveats
- No other patient-specific factors (weight, sex, renal function, or mild-to-moderate hepatic impairment) require dose adjustment according to FDA labeling 1
- The 28 mg starting dose for elderly patients is a precautionary measure, not based on specific pharmacokinetic data showing harm at higher doses
- Genetic or metabolic factors have not been validated as reliable predictors of optimal starting dose 6
- Treatment should continue for at least 6 months after symptom improvement 2