What is the recommended dosing schedule, administration requirements, and contraindications for Bellsomra (esketamine) nasal spray in adults with treatment‑resistant major depressive disorder?

Bellsomra (Esketamine) Dosing for Treatment-Resistant Depression

Critical Clarification

The medication in question is Spravato (esketamine nasal spray), not Bellsomra—Bellsomra is suvorexant, a sleep medication. The following addresses esketamine (Spravato) dosing.

Recommended Dosing Schedule

For treatment-resistant depression in adults, esketamine is dosed at 56 mg or 84 mg intranasally, administered twice weekly for 4 weeks (induction), then once weekly for 4 weeks (weeks 5-8), followed by individualized maintenance dosing of either once weekly or every 2 weeks starting at week 9. 1

Induction Phase (Weeks 1-4)

• Starting dose: 56 mg or 84 mg administered twice per week 1
• Adults <65 years: typically start at 56 mg 2
• Adults ≥65 years: start at 28 mg 2
• Each dose requires 2 devices (56 mg) or 3 devices (84 mg), with 5-minute rest between each device 1

Maintenance Phase

• Weeks 5-8: 56 mg or 84 mg once weekly 1
• Week 9 onward: 56 mg or 84 mg every 2 weeks OR once weekly, based on clinical response 1
• Evidence of therapeutic benefit must be evaluated at the end of induction phase to determine continuation 1

Alternative Indication: Acute Suicidal Ideation/Behavior

• Fixed dose: 84 mg twice weekly for 4 weeks only 1
• May reduce to 56 mg twice weekly based on tolerability 1
• Use beyond 4 weeks has not been systematically evaluated for this indication 1

Administration Requirements

Pre-Administration Preparation

• Fasting requirements: No food for at least 2 hours before administration; no liquids for at least 30 minutes prior 1
• Nasal medication timing: If nasal corticosteroids or decongestants are needed, administer at least 1 hour before esketamine 1
• Blood pressure baseline: Assess before each dose 1

During Administration

• Do NOT prime the nasal spray device before use (prevents medication loss) 1
• Administer under direct healthcare provider supervision 1
• Use multiple devices with 5-minute intervals between each 1

Post-Administration Monitoring (Mandatory 2-Hour Observation)

• Blood pressure monitoring: Reassess at approximately 40 minutes post-dose (corresponds to peak concentration) and as clinically warranted 1
• Sedation monitoring: Observe for sedation or loss of consciousness using standardized scales; 48-61% of patients develop sedation 1
• Dissociative symptoms: Monitor throughout observation period; occurs in 24-25% of patients 1, 3
• Respiratory monitoring: Watch for respiratory depression, though incidence is rare (1 per 20,000 treatment sessions); pulse oximetry recommended 4
• Discharge criteria: Patient must be clinically stable for at least 2 hours; if blood pressure is decreasing and patient appears stable, may discharge 1

Post-Discharge Restrictions

• No driving or operating machinery until the next day after restful sleep 1

Contraindications (Absolute)

Esketamine is absolutely contraindicated in patients with: 1

• Aneurysmal vascular disease (thoracic/abdominal aorta, intracranial, peripheral arterial vessels)
• Arteriovenous malformation
• History of intracerebral hemorrhage
• Hypersensitivity to esketamine, ketamine, or excipients

Relative Contraindications/Precautions

• Uncontrolled hypertension: If baseline BP >140/90 mmHg, carefully weigh risks versus benefits; do NOT administer if BP increase poses serious risk 1
• Increased intracranial pressure: Do not administer if ICP elevation poses serious risk 1

Patient Selection Criteria

Esketamine is reserved EXCLUSIVELY for adults with treatment-resistant depression who have failed at least 2 adequate antidepressant trials. 5, 6

Definition of Adequate Trial

• Different mechanisms of action (per Neuroscience-based Nomenclature) 5
• Minimum approved dosage for at least 4 weeks duration 5
• Improvement <25% on validated depression scales for both medications 5
• Failed psychotherapy does NOT count toward treatment-resistant definition 5

Critical Exclusions

• NOT indicated for initial depression treatment 5, 6
• Patients who have not failed adequate antidepressant trials should NOT receive esketamine 5

Common Pitfalls and Safety Considerations

Most Common Adverse Events

• Headache (36.9%), dizziness (33.9%), nausea (33.6%), dissociation (25.5%), nasopharyngitis (23.8%), somnolence (23.1%) 3
• Nausea and vomiting risk necessitates pre-dose fasting 1

Long-Term Safety Concerns Requiring Surveillance

• Abuse/misuse potential: Esketamine is Schedule 2 controlled substance; monitor throughout treatment 5, 1
• Neurocognitive effects: Unknown with long-term use 5
• Urologic toxicity: Possible with chronic administration 5
• Substance use disorder development: Assess regularly 5

REMS Program Requirement

• Esketamine is available ONLY through a restricted REMS program due to sedation and abuse risks 1
• Must be administered in certified healthcare settings with monitoring capabilities 1

Missed Dose Management

• If no worsening of symptoms: continue current schedule 1
• If worsening during maintenance: consider reverting to previous frequency (e.g., weekly to twice-weekly) 1

Concomitant Medication Requirements

• Must be used in conjunction with oral antidepressant (SSRI or SNRI) for treatment-resistant depression 1, 2
• Continue or initiate second-generation antidepressants alongside esketamine 6