What are the risks of using Monoamine Oxidase Inhibitors (MAOIs) and stimulants together?

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MAOIs and Stimulant Use: Contraindicated Combination

Concomitant use of MAOIs and stimulants is absolutely contraindicated due to the risk of severe hypertensive crisis, which can lead to cerebrovascular accidents (stroke) and death. 1, 2

Mechanism of Risk

  • MAOIs prevent the breakdown of norepinephrine and other catecholamines by inhibiting monoamine oxidase enzymes 3
  • Stimulants (including amphetamines, methylphenidate, and sympathomimetic agents like pseudoephedrine and phenylephrine) trigger the release of norepinephrine or act as sympathomimetics 1, 3
  • When combined, this creates a dangerous accumulation of catecholamines that can cause life-threatening blood pressure elevations and hypertensive crisis 1, 3
  • The risk extends to all sympathomimetic drugs including over-the-counter decongestants, diet pills, and illicit stimulants 2, 3

Specific Contraindications

Stimulants that must be avoided with MAOIs include: 1, 2

  • Prescription stimulants: amphetamines, methylphenidate, dextroamphetamine
  • Sympathomimetic decongestants: pseudoephedrine, phenylephrine, oxymetazoline
  • Other sympathomimetics: midodrine, clonidine
  • Bronchodilators: albuterol, salmeterol, terbutaline
  • Illicit stimulants: cocaine, MDMA (ecstasy), methamphetamine

Required Washout Periods

Critical timing requirements to prevent dangerous interactions: 2, 4

  • After stopping an MAOI: Wait at least 2 weeks before starting any stimulant medication 1, 4
  • Before starting an MAOI: Discontinue all stimulants at least 2 weeks prior 4
  • For atomoxetine (a non-stimulant ADHD medication): the same 2-week washout period applies in both directions 4

Clinical Consequences of Violation

Severe hypertensive crisis can manifest as: 1, 3

  • Sudden, severe elevation in blood pressure
  • Severe headache, often described as "thunderclap"
  • Chest pain and palpitations
  • Stroke or intracranial hemorrhage
  • Seizures
  • Hyperthermia
  • Death

Additional Serotonergic Risk

  • Some stimulants (particularly amphetamines and MDMA) also have serotonergic activity, creating additional risk for serotonin syndrome when combined with MAOIs 3, 5
  • Serotonin syndrome presents with mental status changes, autonomic instability (fever, tachycardia), and neuromuscular abnormalities (myoclonus, hyperreflexia, tremor) 1, 5

Special Considerations for ADHD Treatment

For patients requiring both ADHD treatment and an MAOI: 4

  • Atomoxetine (Strattera), a non-stimulant ADHD medication, is also contraindicated with MAOIs and requires the same 2-week washout period 4
  • There are no safe options for combining ADHD stimulant treatment with MAOIs
  • The MAOI must be discontinued with appropriate washout before initiating any stimulant therapy 1, 4

Patient Education Imperatives

Patients on MAOIs must be explicitly warned to avoid: 2, 3

  • All over-the-counter cold and allergy medications containing sympathomimetics
  • Energy drinks and supplements containing stimulants
  • Weight loss products
  • Illicit drugs, particularly cocaine, methamphetamine, and MDMA
  • Informing all healthcare providers (including emergency departments, dentists, and surgeons) about MAOI use before receiving any medications 2

Common Pitfalls to Avoid

  • Never assume a patient has stopped taking stimulants: Verify discontinuation and ensure adequate washout time has elapsed 4
  • Screen for over-the-counter sympathomimetic use: Patients may not recognize decongestants as "stimulants" 2, 3
  • Emergency situations: If a patient on an MAOI requires urgent treatment, inform emergency personnel immediately as many emergency medications (epinephrine, norepinephrine) are contraindicated or require dose adjustments 3
  • Linezolid (antibiotic) has MAOI properties: This creates the same risk when combined with stimulants or serotonergic agents 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Monoamine Oxidase Inhibitors (MAOIs) in the Treatment of Depression and Anxiety

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Serotonin syndrome associated with linezolid use: a case report].

Turk psikiyatri dergisi = Turkish journal of psychiatry, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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