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

Clinical Uses and Safety Concerns

The American Academy of Child and Adolescent Psychiatry recommends MAOIs for the treatment of certain anxiety disorders, including those with high levels of anxiety, and for treatment-resistant depression 1, 2
MAOIs are contraindicated with other MAOIs, SSRIs, SNRIs, TCAs, opioids, stimulants, and certain cough/cold medications due to the risk of serotonin syndrome 1, 2
The American Academy of Pediatrics recommends against concomitant use of MAOIs with SSRIs due to the risk of serotonin syndrome 3
Meperidine is specifically contraindicated with MAOIs due to the risk of serotonin syndrome 4

Drug Interactions and Special Considerations

When switching to or from MAOIs, adequate washout periods are essential, typically 2 weeks, 5 weeks for fluoxetine, to avoid serotonin syndrome and other adverse effects 1
Gradual tapering is recommended when discontinuing MAOIs to avoid withdrawal symptoms 3

Patient Education and Common Pitfalls

Patients on MAOIs must be educated about avoiding over-the-counter medications without consulting a healthcare provider, recognizing signs of serotonin syndrome and hypertensive crisis, and informing all healthcare providers about MAOI use 1, 2
Failure to maintain adequate washout periods when switching between MAOIs and other antidepressants can lead to serotonin syndrome and other adverse effects 1, 2

Monoamine Oxidase Inhibitors (MAOIs)

Introduction to MAOIs

The medications classified as Monoamine Oxidase Inhibitors (MAOIs) include selegiline, phenelzine, linezolid, isocarboxazid, and tranylcypromine 5, 6, 7

Important Drug Interactions

Opioids (especially meperidine, tramadol, methadone, fentanyl) should not be combined with MAOIs due to the risk of serotonin syndrome and hypertensive crisis 5

Cold Medicines to Avoid with Antidepressants

Medications to Avoid with MAOIs and SSRIs

Patients taking antidepressants, particularly MAOIs and SSRIs, should avoid decongestants containing sympathomimetics like pseudoephedrine and phenylephrine, as well as cough suppressants containing dextromethorphan, due to risks of hypertensive crisis and serotonin syndrome, as recommended by the American College of Cardiology 8
Avoid all sympathomimetic decongestants (pseudoephedrine, phenylephrine, oxymetazoline) as they can cause dangerous hypertensive crisis when combined with MAOIs, according to the American College of Cardiology 8
Avoid any cold medicine containing stimulants or sympathomimetic agents, as advised by the American College of Cardiology and Circulation 8, 9

Safer Alternatives for Cold Symptoms

Saline nasal sprays or rinses are safe alternatives to decongestants, as recommended by the American College of Cardiology and Circulation 8, 9
Intranasal corticosteroids (fluticasone, mometasone) are generally safe with antidepressants, according to the American College of Cardiology 8
Second-generation antihistamines (loratadine, cetirizine) are generally safer than first-generation antihistamines, as suggested by Circulation 9

Medications to Use with Caution with SSRIs

Use sympathomimetic decongestants (pseudoephedrine, phenylephrine) with caution as they may increase blood pressure, as recommended by the American College of Cardiology 8
Consider lower doses if these must be used, as advised by Circulation 9

Treatment of Depression and Anxiety with MAOIs

Indications and Treatment Algorithms

The American College of Physicians recommends first-line options of tricyclic antidepressants or fluoxetine for moderate to severe depression, with MAOIs considered as third-line options 10
The National Institute of Health suggests second-line options of other SSRIs, SNRIs, or bupropion for depression treatment 11
For medically unexplained somatic complaints, psychological treatment based on CBT principles should be considered first for patients who do not meet criteria for depressive disorder 10
Antidepressant treatment should not be stopped before 9-12 months after recovery, according to the American Psychiatric Association 10

Treatment Duration and Monitoring

The American Medical Association recommends that treatment with MAOIs often has to be long-term 10

MAOIs and Stimulant Use: Contraindicated Combination

Mechanism of Risk and Contraindications

The American Academy of Child and Adolescent Psychiatry recommends avoiding concomitant use of MAOIs and stimulants due to the risk of severe hypertensive crisis, which can lead to cerebrovascular accidents and death, as MAOIs prevent the breakdown of norepinephrine and other catecholamines, while stimulants trigger the release of norepinephrine or act as sympathomimetics 12
Stimulants, including amphetamines, methylphenidate, and sympathomimetic agents like pseudoephedrine and phenylephrine, can cause life-threatening blood pressure elevations and hypertensive crisis when combined with MAOIs 13

Clinical Consequences and Required Washout Periods

Severe hypertensive crisis can manifest as sudden, severe elevation in blood pressure, severe headache, chest pain, palpitations, stroke, seizures, hyperthermia, and death, with symptoms often described as "thunderclap" headache, and can be triggered by the combination of MAOIs and stimulants 12, 13, 14
The American Academy of Child and Adolescent Psychiatry recommends waiting at least 2 weeks before starting any stimulant medication after stopping an MAOI, and discontinuing all stimulants at least 2 weeks prior to starting an MAOI, to prevent dangerous interactions 12

Additional Serotonergic Risk and Special Considerations

Some stimulants, particularly amphetamines and MDMA, also have serotonergic activity, creating additional risk for serotonin syndrome when combined with MAOIs, which presents with mental status changes, autonomic instability, and neuromuscular abnormalities 14
The American Academy of Child and Adolescent Psychiatry recommends that patients on MAOIs must be explicitly warned to avoid all over-the-counter cold and allergy medications containing sympathomimetics, energy drinks and supplements containing stimulants, weight loss products, and illicit drugs, particularly cocaine, methamphetamine, and MDMA, and to inform all healthcare providers about MAOI use before receiving any medications 12, 14

Safe Allergy Medications with SSRIs

Recommended Allergy Medications

The American Academy of Otolaryngology-Head and Neck Surgery recommends second-generation antihistamines like cetirizine, loratadine, and fexofenadine as the best first-line choice for allergy management in patients taking SSRIs, due to their safety and efficacy with no significant drug interactions 15
Second-generation antihistamines are generally safer than first-generation options due to reduced sedation and anticholinergic effects, according to the American Gastroenterological Association 16
The American Academy of Otolaryngology-Head and Neck Surgery suggests that intranasal corticosteroids, such as fluticasone and mometasone nasal sprays, are safe to use with SSRIs and can be continued without concern 15
Azelastine and olopatadine nasal sprays are safe alternatives to oral antihistamines, with comparable somnolence rates to placebo, and do not significantly increase when combined with SSRIs, as recommended by the American Academy of Otolaryngology-Head and Neck Surgery 15

Medications to AVOID or Use with Extreme Caution

The European Society of Cardiology advises against combining SSRIs with MAOIs due to the risk of life-threatening serotonin syndrome 17
First-generation antihistamines, such as diphenhydramine, hydroxyzine, and chlorpheniramine, may cause additive sedation and cognitive effects, particularly in elderly patients, and should be used with caution, according to the American Academy of Allergy, Asthma, and Immunology 18, 16

MAOIs in Anxiety Treatment

Introduction to MAOIs

The American Psychiatric Association recommends MAOIs as third- to fifth-line treatments for anxiety disorders due to safety concerns, reserved for treatment-resistant cases 19

Efficacy of MAOIs

MAOIs are effective for continuous daily treatment of specific anxiety disorders, particularly agoraphobia, panic disorder, and mixed anxiety-depressive states 19

Life-Threatening Drug Interactions with MAOIs

Critical Contraindications by Drug Class

All sympathomimetic decongestants, including pseudoephedrine, phenylephrine, and oxymetazoline, are contraindicated with MAOIs due to the risk of hypertensive crisis, as recommended by the American Heart Association 20
Atypical antipsychotics, such as clozapine and olanzapine, can elevate blood pressure and interact adversely with MAOIs, and should be used with caution, according to the American College of Cardiology 20