Is it safe to take Vyvanse (lisdexamfetamine) and Sunosi (solriamfetol) together?

Combining Vyvanse and Sunosi: Safety Considerations

The combination of Vyvanse (lisdexamfetamine) and Sunosi (solriamfetol) should be approached with significant caution due to overlapping mechanisms that increase cardiovascular and psychiatric risks, though no absolute contraindication exists. Both medications increase catecholamine activity—Vyvanse releases dextroamphetamine (increasing dopamine and norepinephrine), while Sunosi inhibits reuptake of dopamine and norepinephrine 1, 2.

Primary Safety Concerns

Cardiovascular Risks

• Both medications independently elevate heart rate and blood pressure, creating additive cardiovascular stress when combined 3, 4.
• The American Academy of Child and Adolescent Psychiatry emphasizes caution when combining medications with similar mechanisms, particularly stimulants that affect catecholamine systems 3.
• Common adverse effects of both drugs include elevated heart rate, increased blood pressure, and cardiovascular stimulation 3, 5.
• Contraindication exists for patients with unmanaged hypertension when using stimulant medications 3.

Psychiatric and CNS Effects

• Overlapping side effect profiles include anxiety, insomnia, irritability, headache, and decreased appetite 3, 5, 2.
• The American Academy of Child and Adolescent Psychiatry recommends careful monitoring when combining medications that affect neurotransmitter systems, starting at low doses and increasing slowly 3.
• Risk of behavioral activation and agitation is heightened, particularly early in treatment or with dose increases 3.

Serotonin Syndrome Considerations

• While neither medication is primarily serotonergic, caution should be exercised when combining any medications affecting neurotransmitter systems 6.
• The American Academy of Child and Adolescent Psychiatry specifically warns about combining stimulants (including amphetamine class medications like Vyvanse) with other agents affecting monoamine systems 3.
• Symptoms of excessive catecholaminergic activity (hypertension, tachycardia, agitation, tremors) should be monitored closely 3.

Clinical Management Algorithm

Pre-Treatment Assessment

• Obtain baseline cardiovascular evaluation including blood pressure, heart rate, and ECG if indicated 3.
• Screen for contraindications: uncontrolled hypertension, cardiovascular disease, glaucoma risk, history of substance abuse 3.
• Assess for psychiatric conditions that may be exacerbated (anxiety disorders, bipolar disorder) 3.

Initiation Strategy

• Start with the lowest effective dose of each medication rather than combining full doses initially 3.
• Consider staggering introduction—establish tolerance to one medication before adding the second 3.
• Monitor closely in the first 24-48 hours after any dose adjustment, as this is when adverse effects are most likely 3.

Ongoing Monitoring

• Check blood pressure and heart rate at each visit, particularly during dose titration 3.
• Monitor for psychiatric symptoms: anxiety, insomnia, agitation, mood changes 3, 5.
• Assess for signs of excessive stimulation: tremor, restlessness, decreased appetite, weight loss 3, 2.
• Screen for abuse potential, as both medications have controlled substance status 7.

Common Pitfalls to Avoid

• Do not combine with monoamine oxidase inhibitors—this is absolutely contraindicated 3.
• Avoid in patients with acute angle-closure glaucoma risk 3.
• Do not ignore cardiovascular symptoms—chest pain, palpitations, or syncope require immediate evaluation 3.
• Be cautious in patients taking other medications that prolong QT interval or affect blood pressure 3.
• Monitor for signs of dependence, particularly with prolonged amphetamine administration 7.

Special Populations

Pregnancy and Breastfeeding

• Amphetamines cross the placental barrier and may cause fetal harm including increased risk for gastroschisis and preeclampsia 7.
• Continued stimulant use in the second half of pregnancy may increase preterm birth risk 7.
• Consider non-pharmacological interventions during pregnancy 7.
• Monitor infants for irritability, insomnia, and feeding difficulties if maternal use occurred 7.

Pediatric Considerations

• CNS stimulants are associated with weight loss and slowing of growth rate—closely monitor growth parameters 7.
• Younger children may be more susceptible to behavioral activation 3.

Clinical Context

While solriamfetol has demonstrated efficacy and favorable safety as monotherapy for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea 8, 5, and lisdexamfetamine is effective for ADHD 6, the combination lacks specific safety data from controlled trials. The decision to combine these medications should be reserved for cases where monotherapy has failed and the potential benefits clearly outweigh the cardiovascular and psychiatric risks 3.