What is the recommended washout interval before initiating dextro‑amphetamine/amphetamine (Adderall) or methylphenidate (Ritalin) after completing linezolid therapy?

Washout Period After Linezolid Before Starting Adderall or Ritalin

Wait at least 2 weeks after stopping linezolid before initiating dextroamphetamine/amphetamine (Adderall) or methylphenidate (Ritalin). 1

Rationale for the 2-Week Washout

Linezolid is a reversible monoamine oxidase (MAO) inhibitor that requires a minimum 2-week washout period before starting any adrenergic or serotonergic medications. 1 This recommendation is explicitly stated in the British Thoracic Society guidelines, which contraindicate concomitant use of linezolid with drugs that inhibit monoamine oxidases A or B "or within 2 weeks of taking any such medicinal product." 1

Why This Matters for Stimulants

• Both Adderall (amphetamine salts) and Ritalin (methylphenidate) are adrenergic agents that increase catecholamine concentrations in the central nervous system. 2
• Linezolid exhibits both MAO-A and MAO-B inhibitory effects, which can potentiate the effects of sympathomimetic agents and increase the risk of hypertensive crisis and serotonin syndrome. 2, 3
• The reversible nature of linezolid's MAO inhibition means enzyme activity gradually returns to normal after discontinuation, but this process requires approximately 2 weeks for adequate recovery. 1

Clinical Evidence and Risk Assessment

Real-World Safety Data

A 2024 case series examining 194 encounters with linezolid and dextroamphetamine found only one confirmed case and two possible cases of serotonin syndrome, suggesting the absolute risk may be lower than theoretical concerns. 4 However, this study examined concurrent use rather than sequential administration, and the mean duration of overlap was only 7 days. 4

Documented Interaction Severity

• Linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. 2
• Foods containing high concentrations of tyramine should be avoided during linezolid therapy due to its MAO inhibitory properties. 2
• While adrenergic drug interactions with linezolid are less common in clinical practice than serotonergic interactions, monitoring for signs of hypertension remains important. 5

Practical Management Algorithm

Step 1: Confirm Linezolid Discontinuation

• Document the exact date of the last linezolid dose 1
• Verify the patient completed or discontinued therapy (typical duration is up to 28 days) 2

Step 2: Assess Patient-Specific Risk Factors

• Screen for uncontrolled hypertension, pheochromocytoma, carcinoid tumor, thyrotoxicosis, or acute confusional states—all contraindications that persist beyond linezolid use 1
• Check baseline blood pressure and pulse 2
• Review for any residual linezolid adverse effects, particularly myelosuppression if treatment exceeded 14 days 2

Step 3: Wait the Full 2-Week Period

• Count 14 full days from the last linezolid dose before prescribing any stimulant medication 1
• During this washout, avoid all tyramine-rich foods and other adrenergic/serotonergic agents 1, 2

Step 4: Initiate Stimulant Therapy Cautiously

• Start with the lowest effective dose of Adderall or Ritalin 6
• Monitor blood pressure and pulse closely during the first week of stimulant initiation 5, 2
• Educate the patient on symptoms of hypertensive crisis (severe headache, chest pain, palpitations, confusion) 5, 3

Critical Caveats

Do not shorten the 2-week washout period even if the patient received only a brief course of linezolid. 1 The guideline contraindication applies regardless of linezolid duration or dose.

If urgent ADHD treatment is needed during the washout period, consider non-stimulant alternatives such as atomoxetine or alpha-2 agonists (guanfacine, clonidine), which do not carry the same adrenergic interaction risk. 7 These agents require 6-12 weeks to reach full efficacy but can be initiated immediately after linezolid discontinuation. 7

The 2-week washout applies equally to both immediate-release and extended-release formulations of Adderall and Ritalin. 6 Extended-release preparations (Adderall XR, Concerta) provide 8-12 hours of symptom coverage but do not alter the pharmacodynamic interaction risk with residual MAO inhibition. 6