What is the reason for a patient, likely between 6 and 25 years old, with a history of Attention Deficit Hyperactivity Disorder (ADHD), to be taking Vyvanse (lisdexamfetamine) and Strattera (atomoxetine) concurrently?

Concurrent Use of Vyvanse and Strattera in ADHD

A patient is prescribed both Vyvanse (lisdexamfetamine) and Strattera (atomoxetine) concurrently when monotherapy with a stimulant alone has failed to adequately control ADHD symptoms, requiring adjunctive nonstimulant therapy to achieve optimal symptom management throughout the day. 1

Primary Clinical Rationale

Inadequate Response to Monotherapy

• The most common reason for combination therapy is insufficient symptom control with a single medication. 2
• Approximately 70% of patients respond to either stimulant or nonstimulant monotherapy, but nearly 10-30% require combination approaches when initial treatment fails. 3
• Combination therapy is typically considered after trials of multiple single agents have not achieved adequate symptom reduction across all functional domains (home, school, work). 2

Mechanism of Complementary Action

• Vyvanse increases presynaptic release of dopamine and norepinephrine after enzymatic conversion in red blood cells, providing robust dopaminergic activity. 3, 4
• Strattera selectively inhibits presynaptic norepinephrine reuptake in the prefrontal cortex without affecting dopamine transporters directly. 5, 6
• The combination targets both dopaminergic and noradrenergic pathways simultaneously, potentially addressing residual symptoms that persist with stimulant monotherapy alone. 2

Specific Clinical Scenarios for Combination Therapy

Extended Duration of Coverage

• Vyvanse provides approximately 12-13 hours of symptom control with once-daily dosing. 3
• Adding Strattera can extend symptom coverage into evening hours and provide more consistent early morning symptom control, as atomoxetine maintains 24-hour noradrenergic activity. 5, 6
• This is particularly valuable for adolescents and young adults who need symptom control for driving, evening studying, or social functioning. 1

Partial Response with Residual Symptoms

• Some patients achieve improvement in hyperactivity/impulsivity with stimulants but continue to struggle with inattention or executive function deficits. 2
• Strattera specifically targets prefrontal cortex noradrenergic function, which may address residual inattention symptoms not fully controlled by Vyvanse alone. 6

Comorbid Conditions

• Patients with ADHD plus anxiety disorders may benefit from combination therapy, as atomoxetine does not exacerbate anxiety and may provide additional anxiolytic effects. 6
• Strattera is particularly useful when comorbid tic disorders are present, as it does not worsen tics unlike higher doses of stimulants alone. 5

Treatment Strategy and Dosing Approach

Typical Sequencing

• Methylphenidate or amphetamine stimulants (including Vyvanse) are most commonly used as the initial medication, with atomoxetine added for augmentation rather than switching. 2
• Vyvanse is started at 20-30 mg daily and titrated by 10 mg weekly to a maximum of 70 mg daily. 3
• Strattera is typically initiated at lower doses (0.5 mg/kg/day) and gradually increased to the target dose of 1.2 mg/kg/day to minimize gastrointestinal side effects. 5

FDA-Approved Adjunctive Therapy Considerations

• Only extended-release guanfacine and extended-release clonidine have FDA approval specifically for adjunctive use with stimulants; the combination of Vyvanse and Strattera remains off-label for combination therapy. 1
• However, limited evidence supports the safety and potential efficacy of atomoxetine combined with stimulants, with no serious adverse events reported in published case series. 2

Safety and Tolerability Profile

Cardiovascular Monitoring

• Both medications can affect heart rate and blood pressure: Vyvanse typically increases both by 1-4 mm Hg and 1-2 beats per minute, while Strattera may cause similar mild increases. 1, 6
• Obtain personal and family cardiac history before initiating combination therapy, and monitor vital signs regularly, as the combined cardiovascular effects are additive but generally remain clinically insignificant in most patients. 1

Common Adverse Effects

• The combination may increase the likelihood of appetite suppression, gastrointestinal symptoms (nausea, abdominal pain), and initial somnolence. 1, 5
• Strattera's gastrointestinal side effects are typically transient and can be minimized by slower dose titration and taking the medication with food. 5

Psychiatric Monitoring

• Atomoxetine carries an FDA black box warning for increased suicidal ideation in children and adolescents, requiring close monitoring especially when initiating or adjusting doses. 1, 6
• Screen for emerging mood symptoms, irritability, or behavioral changes during combination therapy. 6

Special Considerations for Adolescents and Young Adults

Abuse and Diversion Risk

• Vyvanse is specifically recommended over immediate-release amphetamines in adolescents due to its prodrug formulation that significantly reduces abuse potential. 1, 3
• Adding Strattera, which has no abuse potential and is not a controlled substance, provides additional therapeutic benefit without increasing diversion risk. 6, 7
• This combination is particularly appropriate for college-age patients (ages 18-25) where peer pressure for stimulant diversion is highest. 3

Evidence Quality and Limitations

Limited Prospective Data

• Published evidence for stimulant-atomoxetine combination therapy consists primarily of retrospective case series and only one small prospective randomized controlled trial, limiting definitive conclusions about efficacy. 2
• Most studies report improved ADHD symptom control in some but not all patients receiving combination therapy. 2
• No serious adverse events have been reported in published combination therapy studies, suggesting acceptable short-term safety. 2

Common Clinical Pitfalls

• Do not assume combination therapy is first-line treatment—it should only be considered after adequate trials of monotherapy with at least one stimulant and preferably one nonstimulant have failed. 2
• Do not neglect to taper Strattera if discontinuing—abrupt cessation may cause discontinuation symptoms, though atomoxetine has lower risk than alpha-2 agonists. 5
• Do not overlook the 2-4 week delay in atomoxetine's full therapeutic effect—patients and families need counseling that Strattera's benefits are not immediate like Vyvanse. 5, 6
• Do not ignore substance abuse screening in adolescents and young adults before prescribing this combination, as undetected substance use disorders require assessment off substances before ADHD treatment. 1