isocarboxazid

General Information

Isocarboxazid (brand Marplan) is an irreversible, nonselective monoamine oxidase inhibitor (MAOI) antidepressant indicated for major depressive disorder in adults who have not responded to other antidepressants (label).

MAOIs can be effective in some cases of treatment-resistant depression and atypical depression, but they have high-stakes drug and dietary interaction risks that shape patient selection and counseling (label/clinical).

The label states pharmacokinetic information is not available, so safety guidance centers on interaction avoidance, washout timing, and hypertensive crisis recognition rather than PK-based titration (label).

Because MAOI interactions can be life-threatening, many clinicians reserve isocarboxazid for settings that can provide written diet and interaction lists, confirm understanding, and offer rapid access for urgent symptoms (clinical).

The compare view, isocarboxazid evidence feed, and isocarboxazid print page support counseling and safety planning when an MAOI is being considered.

MAOIs are less commonly used than SSRIs/SNRIs because of dietary and drug interaction constraints. When an MAOI is selected, safety depends on meticulous medication reconciliation, clear written instructions, and timely recognition of hypertensive crisis or serotonin syndrome.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Irreversibly inhibits monoamine oxidase (MAO-A and MAO-B), increasing synaptic monoamines (serotonin, norepinephrine, dopamine) (mechanism).

Because inhibition is irreversible, physiologic recovery requires new enzyme synthesis; interaction risk can persist after discontinuation, so washout planning is central to safe use (label/clinical).

• Irreversible MAO-A/MAO-B inhibition (MAOI class).

Metabolism and Pharmacokinetics

• Label states pharmacokinetic information for Marplan is not available (label).
• Clinical effects on MAO activity can outlast the presence of drug in plasma because inhibition is irreversible; switching requires washout planning (label/clinical).

Dosing and Administration

• Label trials initiated at 10 mg twice daily, with increases every 2–4 days as tolerated until effect, up to 80 mg/day in divided doses (label).
• Dosing changes and discontinuation are often paired with explicit washout instructions because of high-risk interactions with serotonergic and sympathomimetic medications (label/clinical).
• Dietary and medication interaction precautions are typically continued for at least 14 days after stopping because MAO inhibition persists until new enzyme is synthesized (label/clinical).

Monitoring & Labs

• Before starting: review all prescription/OTC/supplement products and provide a written “do-not-combine” list; confirm understanding with teach-back (clinical).
• Diet: counsel on tyramine restriction and continue dietary precautions for at least 14 days after discontinuation (label/clinical).
• Vitals: monitor orthostatic blood pressure during titration and after dose changes; counsel on hydration and slow position changes (label/clinical).
• Emergency symptoms (severe headache, chest pain, palpitations, stiff neck, fever, marked agitation/confusion) require urgent evaluation because they can signal hypertensive crisis or serotonin syndrome (label/clinical).
• Mood: monitor for suicidality early in treatment and for mania/hypomania activation in patients with bipolar risk (class/clinical).

Switching plans should document washout timing, especially with longer half-life agents like fluoxetine, to reduce severe interaction risk (label/clinical).

Adverse Effects

Interactions

• Many serotonergic and sympathomimetic medications are contraindicated or strongly discouraged due to life-threatening reactions (label).
• Fluoxetine requires a prolonged washout before MAOI initiation because of fluoxetine/norfluoxetine long elimination half-life (label).
• Tyramine-containing foods and some supplements can precipitate hypertensive crisis; dietary counseling is a core safety intervention (label/clinical).

Other Useful Information

• In depression treatment algorithms, MAOIs are typically positioned after multiple standard antidepressant trials and augmentation approaches (APA/CANMAT/clinical).
• Patients and caregivers often benefit from written “avoid” lists and a clear plan for urgent symptoms (severe headache, chest pain, confusion, severe agitation, fever) (clinical).
• Many MAOI programs recommend medical alert identification and proactive communication with primary care, dentistry, and anesthesia teams to avoid contraindicated decongestants, analgesics, and procedural medications (clinical).

References

1. MARPLAN (isocarboxazid) tablets prescribing information — DailyMed (2023)
2. Consensus recommendations for MAOI safety and dietary management — Journal of Clinical Psychopharmacology (2022)
3. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
4. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)