What are the guidelines for introducing Sunosi (solriamfetol) to a patient with narcolepsy already taking Adderall (amphetamine and dextroamphetamine)?

Adding Sunosi (Solriamfetol) to Adderall for Narcolepsy

Initiate solriamfetol at 75 mg once daily upon awakening while continuing Adderall, then titrate to 150 mg after at least 3 days based on response—this add-on strategy is supported by real-world evidence showing efficacy was the primary driver for combination therapy in 95% of cases. 1, 2

Pre-Initiation Requirements

Before starting solriamfetol, you must ensure blood pressure is adequately controlled, as solriamfetol increases both systolic and diastolic blood pressure plus heart rate in a dose-dependent manner. 1 This is particularly critical when adding to Adderall, which also elevates cardiovascular parameters. 1

• Measure baseline blood pressure and heart rate at rest before prescribing solriamfetol. 1
• Control any existing hypertension before initiating combination therapy. 1
• Assess cardiovascular risk factors including history of cardiovascular disease, cerebrovascular disease, diabetes, hyperlipidemia, and advanced age, as these patients require extra caution with dual stimulant therapy. 1

Dosing Algorithm for Narcolepsy

Starting dose: Initiate solriamfetol at 75 mg once daily upon awakening, taken with or without food, while maintaining the current Adderall regimen. 1 Real-world data from 70 patients with narcolepsy showed 86% of physicians initiated at 75 mg/day when using solriamfetol. 2

Titration schedule: Double the dose to 150 mg once daily after a minimum of 3 days if response is inadequate and tolerability is acceptable. 1 Most patients (67%) required only one dose adjustment, reaching stable dosing over a median of 14 days. 2

Maximum dose: 150 mg once daily is the maximum recommended dose, as dosages above 150 mg do not provide increased effectiveness sufficient to outweigh dose-related adverse reactions. 1

Timing: Administer solriamfetol upon awakening and avoid taking within 9 hours of planned bedtime to prevent sleep interference. 1

Evidence Supporting Add-On Therapy

The American Academy of Sleep Medicine provides a STRONG recommendation for solriamfetol use in narcolepsy based on high-quality evidence from 3 RCTs demonstrating clinically significant improvements in excessive daytime sleepiness and disease severity. 3

Real-world evidence specifically supports the add-on strategy you're considering:

• 29% of patients with narcolepsy received solriamfetol as add-on therapy to existing EDS medications. 2
• Efficacy profile was the primary reason for add-on initiation in 95% of cases (19 of 20 patients). 2
• 90% of patients continued solriamfetol at data collection, indicating sustained benefit. 2

Managing the Combination

Continue Adderall unchanged initially: Unlike transitioning strategies where wake-promoting agents are discontinued abruptly (64% of cases) or stimulants are tapered (56% of cases), add-on therapy maintains the existing regimen. 2 This allows assessment of incremental benefit from solriamfetol without destabilizing current symptom control.

Monitor for additive effects: Both medications increase dopamine and norepinephrine activity through different mechanisms—Adderall releases monoamines while solriamfetol inhibits their reuptake. 4 This complementary action can enhance efficacy but requires vigilant monitoring for:

• Blood pressure elevations (check at each visit during titration). 1
• Heart rate increases (monitor regularly). 1
• Insomnia (common with solriamfetol at 15-20% incidence; ensure 9-hour window before bedtime). 3, 1
• Decreased appetite (occurs in 10-15% with solriamfetol). 3, 1
• Headache (most common adverse event, typically mild-moderate and resolving within 2 weeks). 3, 1, 5

Critical Safety Considerations

Contraindication: Do not use solriamfetol if the patient is taking MAO inhibitors or within 14 days of discontinuing them due to hypertensive reaction risk. 1

Abuse potential: Solriamfetol is Schedule IV (lower abuse potential than Adderall's Schedule II), but combining two controlled substances requires documentation of medical necessity and monitoring for misuse. 3, 1

Pregnancy considerations: Based on animal data, solriamfetol may cause fetal harm; human data are insufficient. 3 The risk-benefit balance differs for pregnant and breastfeeding women. 3

Expected Timeline and Outcomes

Solriamfetol demonstrates early and sustained reductions in excessive sleepiness with effects generally sustained through 52 weeks. 5 Most adverse reactions occur within 2 weeks of treatment initiation and resolve within 2 weeks. 5

Efficacy measures: Solriamfetol produced robust improvements on Maintenance of Wakefulness Test (6.1-11.2 minutes increase at 150 mg), Epworth Sleepiness Scale (3.7-4.9 point reduction at 150 mg), and Patient Global Impression of Change (33-52% improvement at 150 mg) regardless of cataplexy status. 6

When to Reassess

If inadequate response persists after reaching 150 mg solriamfetol for at least 1 week, consider adjusting the Adderall dose or exploring alternative combinations rather than exceeding the maximum solriamfetol dose. 1 The combination approach allows optimization of both agents within their therapeutic ranges while leveraging complementary mechanisms of action. 4