Isocarboxazid (Marplan) is an antidepressant drug that belongs to the Monoamine Oxidase Inhibitors class of medicines. It is used in the treatment of depression in people intolerant to or have an inadequate response to other antidepressant medications.

Isocarboxazid (Marplan) Uses:

• Used for treating depression resistant to other first-line medications.

Isocarboxazid (Marplan) Dose in Adults

Isocarboxazid (Marplan) Dose in the treatment of Depression: Oral:

• Initial: 10 mg twice daily.
• By the end of the first week, the dose may be increased to a maximum of 40 mg/day by adding 10 mg/day to the dose every two to four days. The medication needs to be divided into two to four divided doses.
• The dose may be increased after the first week by up to 20 mg/week for a total of 60 mg/day.
• It may take 3 to 6 weeks to see the desired effects.
• The dose may be reduced once the maximum clinical effect is seen.
• If there is a minimal response within six weeks, additional titration is unlikely to be beneficial.
• Note: Use with caution in patients exceeding doses greater than 40 mg/day.

Discontinuation of therapy:

• Antidepressants must not be abruptly discontinued. Treatment must be gradually tapered off to minimize the reemergence of old symptoms as well as to reduce the chances of withdrawal effects.
• Although data regarding an ideal tapering regimen is limited, antidepressants with a short half-life such as MAO inhibitors must be tapered very conservatively.
• WFSBP recommendations advise weaning off antidepressants over a 4- to 6-month period.
• If, while reducing the dose, the patient develops withdrawal symptoms, the previous dose should be resumed and a more gradual tapering regimen should be initiated.

MAO inhibitor recommendations:

• While shifting from an MAO inhibitor to another antidepressant or vice versa, a time-lapse of 7 - 14 days should be considered before an alternative antidepressant is initiated.
• When switching from fluoxetine to isocarboxazid, a time-lapse of five weeks should be considered.
• When switching from an antidepressant to an MAO inhibitor, a time-lapse of 14 days should be considered.

Use with other MAO inhibitors (such as linezolid or IV methylene blue):

• You shouldn't start giving the medication to patients who are taking linezolid or methylene blue intravenously.
• For patients who require urgent treatment with intravenous methylene blue or linezolid, the benefits and risks should be weighed. Isocarboxazid treatment must be immediately discontinued.
• Patients must be observed for 14 days or until 24 hours have passed after the final dosage of either linezolid or intravenous methylene blue, whichever comes first.
• After 24 hours have passed since your last dosage of IV methylene blue or linezolid, you can restart your isocarboxazid treatment.

Use in Children:

Not indicated.   

Pregnancy Risk Category: C

• Animal reproduction studies have not included any study of the drug.

Use of isocarboxazid during breastfeeding

• The drug's potential for excretion into breastmilk is unknown.
• If indicated by the manufacturer, it should be used only in breastfeeding women.

Dose in Kidney Disease:

Patients with severe renal impairment should not consume. To prevent drug buildup, it may be administered cautiously in mild-to-moderate kidney dysfunction.

Dose in Liver disease:

Avoid the drug in patients with abnormal liver function tests or those with a history of liver disease.   

Common Side Effects of Isocarboxazid (Marplan):

• Central nervous system:
  • Dizziness
  • Headache

Less Common Side Effects of Isocarboxazid (Marplan):

• Cardiovascular:
  • Orthostatic Hypotension
  • Palpitations
  • Syncope
• Central Nervous System:
  • Disturbed Sleep
  • Drowsiness
  • Anxiety
  • Chills
  • Feeling Of Heaviness
  • Forgetfulness
  • Hyperactivity
  • Lethargy
  • Myoclonus
  • Paresthesia
  • Sedation
• Dermatologic:
  • Diaphoresis
• Gastrointestinal:
  • Xerostomia
  • Constipation
  • Nausea
  • Diarrhea
• Genitourinary:
  • Urinary Frequency
  • Impotence
  • Urinary Hesitancy
• Neuromuscular & Skeletal:
  • Tremor

Contraindications to Isocarboxazid (Marplan):

• Hypersensitivity to isocarboxazid and any component of the formulation
• Hypertension and cardiovascular disease;
• Cerebrovascular disease (suspected, confirmed).
• Headache
• A history of liver disease or abnormal liver function tests
• Pheochromocytoma
• Grave renal impairment
• Concurrent use of:
  • Antihistamines
  • Antihypertensives
  • bupropion
  • buspirone
  • Caffeine
  • CNS depressants (including opioids and ethanol)
  • dextromethorphan
  • Diuretics
  • General anesthesia for elective surgery (discontinue isocarboxazid more than 10 days before elective surgery).
  • Local vasoconstrictors
  • meperidine
  • MAO inhibitors and dibenzazepine derivatives, including:
    • Amitriptyline
    • Clomipramine
    • Desipramine
    • imipramine
    • nortriptyline
    • Protriptyline
    • Doxepin
    • Carbamazepine
    • Cyclobenzaprine
    • amoxapine
    • Maprotiline
    • Trimipramine)
  • SSRIs and SNRIs
  • Hypotension (spinal anesthesia) may be exaggerated
  • Sympthomimetics include amphetamines (cocaine, phenylephrine and pseudoephedrine), or
  • Related compounds (methyldopa and reserpine; levodopa; tryptophan); or
  • Foods high in tyramine are not recommended
• Bupropion: Between MAO inhibitor discontinuation, and bupropion initiation, at least 14 days must pass.
• Buspirone: Between isocarboxazid discontinuation, and buspirone initiation, at least 10 days must pass.
• MAO inhibitors and dibenzazepine derivatives: A minimum of one week must elapse before another MAO inhibitor, dibenzazepine derivative, or isocarboxazid is used.
• Between MAO inhibitor discontinuation, meperidine use, and meperidine usage, it should be at least 2 weeks.
• SSRIs and SNRIs: Between the discontinuation or beginning of isocarboxazid or sertraline, at least two weeks must elapse. 
• Between the cessation of fluoxetine treatment and the induction of isocarboxazid, it should be at least five weeks. 
• Between the discontinuation of a SNRI, and the initiation isocarboxazid, at least one week must elapse. 
• Between the discontinuation or initiation of isocarboxazid, at least two weeks must elapse.

Warnings and precautions

• Hypertensive crisis
  • Hypertension can lead to fatalities in patients.
  • Some patients may experience severe headaches, nausea, vomiting and neck stiffness. Hypertension should be monitored closely.
  • Patients who consume food and supplements containing tyramine or tryptophan, Tyrosine, tyrosine and phenylalanine may develop hypertensive crises.
  • Treatment with phentolamine should be considered if the patient has a hypertensive episode.
• Orthostatic hypotension
  • Orthostatic hypotension may be caused by the drug.
  • Hypotension-prone patients and patients who cannot tolerate hypotension should be cautious when using the drug. 
  • Patients with cerebrovascular disease, cardiovascular disease, hypovolemia, bradycardia and patients taking concomitant medication that can cause hypotension are high-risk.
• Angina
  • MAO inhibitors can mask anginal symptoms.
• Diabetes:
  • Patients with diabetes should be cautious when using the drug.
  • Insulin sensitivity may be increased by the drug. You should monitor your blood glucose closely.
• Use of drugs:
  • Patients who have a history of substance abuse or acute alcoholism should be cautious when using the drug.
  • Patients who take excessive amounts of the drug may develop drug dependence and drug toxicity.
• Hypomania and mania:
  • Patients with bipolar disorder may experience mania or hypomania as a result of the drug. It can worsen psychosis.
  • Bipolar patients should stay away from it. Patients exhibiting symptoms of depression should be diagnosed with bipolar illness.
  • Its use in the treatment of bipolar depression has not received FDA approval.
• Renal impairment
  • Patients with severe renal impairment are not advised to take the drug.
  • It should only be used in mild to moderate renal impairment.
• Seizure disorder
  • Treatment can lower the seizure threshold.
  • Patients at high risk for seizures, such as those who have had seizures in the past, are brain damaged, suffered from head trauma or alcoholism, should be cautious about using the drug.
• Thyroid dysfunction
  • Hyperthyroid patients should be cautious when taking the drug.

Monitoring parameters:

• Renal function tests at baseline and periodically thereafter.
• Liver function tests 
• heart rate
• Blood pressure
• mood and suicidal ideation (especially at treatment initiation and after dose adjustment).

Mechanism of action of Isocarboxazid (Marplan):

• It is believed that the drug acts by inhibiting monoamine oxidase.
• MAO inhibitors increase endogenous neurotransmitters such as serotonin and dopamine.   

International Brands of Isocarboxazid:

• Marplan

Isocarboxazid Brand Names in Pakistan:

No Brands Available in Pakistan.