How long after stopping linezolid should I wait before starting Adderall?

Waiting Period After Stopping Linezolid Before Starting Adderall

Wait at least 2 weeks (14 days) after discontinuing linezolid before starting Adderall (amphetamine) to avoid potentially life-threatening serotonin syndrome and hypertensive crisis. 1

Rationale for the 2-Week Washout Period

The 2-week waiting period is based on linezolid's mechanism as a reversible monoamine oxidase (MAO) inhibitor and the time required for complete enzyme recovery:

• Linezolid inhibits both MAO-A and MAO-B enzymes, which are responsible for breaking down neurotransmitters including serotonin, norepinephrine, and dopamine 1, 2, 3
• The contraindication explicitly states avoiding MAO inhibitors within 2 weeks of linezolid use, and this same principle applies in reverse when starting adrenergic agents like Adderall 1
• Adderall is a potent sympathomimetic agent that increases norepinephrine and dopamine release, creating significant risk when MAO enzymes remain inhibited 2

Clinical Risks of Premature Initiation

Starting Adderall too soon after linezolid carries two major risks:

Hypertensive Crisis

• Adrenergic agents combined with MAO inhibition can cause dangerous blood pressure elevations 1, 2, 4
• Even mild MAO inhibitors like linezolid showed blood pressure increases when combined with sympathomimetics pseudoephedrine and phenylpropanolamine 4
• Adderall has substantially more potent adrenergic effects than these agents

Serotonin Syndrome

• Serotonin syndrome has been documented with linezolid and serotonergic agents, with onset ranging from less than 1 day to 20 days after starting combination therapy 5, 6, 2
• While Adderall primarily affects dopamine and norepinephrine, it also has serotonergic activity that could interact with residual MAO inhibition 2
• Symptoms include confusion, agitation, tremor, myoclonus, hyperthermia, tachycardia, and hypertension, and can progress to life-threatening complications 5, 6

Pharmacokinetic Considerations

• Linezolid has an elimination half-life of 5-7 hours, meaning the drug itself clears relatively quickly 4
• However, the critical factor is MAO enzyme recovery, not just drug elimination 1, 3
• Approximately 50% of linezolid appears in urine as metabolites and 35% as parent drug, with complete clearance occurring within days 4
• The 2-week period allows for both drug elimination and full restoration of MAO enzyme function 1

Common Pitfalls to Avoid

Do not assume that because linezolid is a "weak" or "reversible" MAO inhibitor, the interaction risk is negligible 3, 4. Case reports demonstrate serious outcomes even with this "mild" inhibition 5, 6.

Do not start Adderall earlier than 2 weeks even if the patient "feels fine" - MAO enzyme activity may still be suppressed without obvious symptoms 2.

Do not rely on linezolid's short half-life as justification for earlier initiation - enzyme recovery, not drug clearance, determines safety 1.

Clinical Monitoring After Starting Adderall

Once the 2-week washout is complete and Adderall is initiated:

• Monitor blood pressure closely during the first week of Adderall therapy 1, 2
• Watch for signs of serotonin syndrome: agitation, confusion, tremor, myoclonus, diaphoresis, tachycardia, hypertension 5, 6, 2
• Start with the lowest effective dose of Adderall and titrate gradually 7