Adderall XR and Autoimmune Disease: What Clinicians and Patients Need to Know

What the labeling covers

Adderall XR is an extended-release capsule indicated for ADHD in adults and children 6 years and older [2]. The label statements below come from the Adderall immediate-release tablet prescribing information; Adderall XR is a separate extended-release product that contains the same four amphetamine salts [1][2].

The tablet label lists two contraindications: known hypersensitivity to amphetamine or other components of the product, and use of a monoamine oxidase inhibitor or within 14 days of stopping one, because of an increased risk of hypertensive crisis [1].

Blood pressure, heart rate and cardiac history

The tablet label says CNS stimulants raise blood pressure by about 2 to 4 mm Hg and heart rate by about 3 to 6 bpm on average, with larger rises in some patients, and that all treated patients should be monitored for tachycardia and hypertension [1]. It also says sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease treated with CNS stimulants at recommended ADHD doses, and that the drug should be avoided in people with known structural cardiac abnormalities, cardiomyopathy, serious arrhythmia, coronary artery disease or other serious cardiac disease [1].

Raynaud's phenomenon and rheumatology referral

The tablet label says stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon, observed in postmarketing reports and at therapeutic doses in all age groups [1]. Signs and symptoms are usually intermittent and mild, but sequelae include digital ulceration and soft tissue breakdown [1]. The label says careful observation for digital changes is necessary during treatment, and that further clinical evaluation, such as rheumatology referral, may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy [1].

Drugs used to treat autoimmune disease

The interaction sections of the Adderall tablet label cover monoamine oxidase inhibitors, serotonergic drugs (SSRIs, SNRIs, triptans, tricyclic antidepressants, lithium, tramadol, St. John's wort), CYP2D6 inhibitors, and agents that change gastrointestinal or urinary pH [1]. Hydroxychloroquine, methotrexate, TNF inhibitors and JAK inhibitors are not named in that label. We found no study that tested Adderall XR with any of them.

For serotonergic drugs, the tablet label says serotonin syndrome risk is increased and advises starting at lower doses and monitoring at initiation and dose increases [1]. It says co-administration with gastrointestinal alkalinizing agents such as antacids or sodium bicarbonate should be avoided, and that acidifying agents such as ascorbic acid lower amphetamine blood levels and efficacy [1].

Does Adderall XR affect the immune system?

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The tablet label says they are thought to block reuptake of norepinephrine and dopamine into the presynaptic neuron and to increase release of these monoamines, and that the mode of therapeutic action in ADHD is not known [1]. That label describes this stimulant mechanism and does not describe an effect on autoimmune disease activity or immune function [1].