Isocarboxazid is a non-selective and irreversible inhibitor of monoamine oxidase (MAO), an enzyme responsible for breaking down neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain. By inhibiting MAO, isocarboxazid increases the availability of these neurotransmitters in the synaptic cleft, enhancing their effects on mood regulation and emotional stability.

• MAO-A Inhibition: Primarily affects serotonin and norepinephrine, contributing to its antidepressant effects.
• MAO-B Inhibition: Affects dopamine metabolism, which may also play a role in its therapeutic action.

This dual inhibition of MAO-A and MAO-B distinguishes isocarboxazid from selective MAO inhibitors and contributes to its efficacy in treating depression.

Isocarboxazid is primarily indicated for the treatment of major depressive disorder (MDD), particularly in cases where other antidepressants have failed. It is also effective in managing atypical depression, characterized by symptoms such as increased appetite, hypersomnia, and mood reactivity.

• Treatment-Resistant Depression: Isocarboxazid is often reserved for patients who do not respond to first-line antidepressants like SSRIs or SNRIs.
• Atypical Depression: Its efficacy in this subtype of depression is well-documented, making it a preferred choice in such cases.

The dosage of isocarboxazid must be carefully titrated to balance efficacy and minimize side effects. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

• Initial Dose: 10–20 mg once daily, usually taken in the morning.
• Maintenance Dose: Gradually increased to 20–30 mg daily, depending on the patient’s response and tolerance.
• Maximum Dose: 60 mg daily, though higher doses are rarely required.

Important Considerations:

• Isocarboxazid has a long duration of action due to its irreversible inhibition of MAO, so once-daily dosing is sufficient.
• Dose adjustments may be necessary for elderly patients or those with hepatic impairment.

Like all MAOIs, isocarboxazid is associated with a range of side effects, some of which can be serious. Common side effects include:

• Central Nervous System: Dizziness, drowsiness, insomnia, and headache.
• Gastrointestinal: Dry mouth, nausea, constipation, and diarrhea.
• Cardiovascular: Orthostatic hypotension (a significant drop in blood pressure upon standing), which can lead to dizziness or fainting.
• Other: Weight gain, sexual dysfunction, and blurred vision.

Serious Side Effects:

• Hypertensive Crisis: A potentially life-threatening condition caused by the ingestion of tyramine-rich foods or sympathomimetic drugs. Symptoms include severe headache, palpitations, chest pain, and blurred vision.
• Serotonin Syndrome: A rare but dangerous condition resulting from excessive serotonin activity, often due to interactions with other serotonergic drugs.

Isocarboxazid requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Dietary Restrictions: Patients must avoid tyramine-rich foods (e.g., aged cheeses, cured meats, fermented products) to prevent hypertensive crises.
2. Drug Interactions: Concomitant use of other antidepressants, sympathomimetics, or serotonergic agents should be avoided.
3. Medical Conditions: Use with caution in patients with a history of cardiovascular disease, epilepsy, or hepatic impairment.
4. Pregnancy and Lactation: Isocarboxazid should be used during pregnancy only if the potential benefits outweigh the risks. Its safety during breastfeeding is not well-established.
5. Elderly Patients: Lower doses may be required due to increased sensitivity to side effects.

Isocarboxazid has a high potential for drug interactions due to its mechanism of action. Key interactions include:

• Serotonergic Drugs: Concurrent use with SSRIs, SNRIs, or tricyclic antidepressants can lead to serotonin syndrome.
• Sympathomimetics: Drugs like pseudoephedrine or phenylephrine can cause hypertensive crises.
• Tyramine-Containing Foods: As mentioned, tyramine-rich foods can trigger severe hypertension.
• Other MAOIs: Combining isocarboxazid with other MAOIs is contraindicated due to the risk of excessive MAO inhibition.
• CNS Depressants: Alcohol and benzodiazepines may enhance CNS depression.

Isocarboxazid is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Marplan (a well-known brand in the United States and other regions).