Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Marplan® (isocarboxazid) Tablets or any other antidepressant in a child, adolescent or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Marplan is not approved for use in pediatric patients. (See Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and Precautions: Pediatric Use)

Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.


Marplan is contraindicated with: MAO inhibitors or dibenzazepine derivatives; sympathomimetics (including amphetamines); some central nervous system depressants (including narcotics and alcohol); antihypertensive agents, such as thiazide diuretics, antihistaminic, sedative or anesthetic drugs, buproprion HCL, buspirone HCL, dextromethorphan, over-the-counter drugs that contain vasoconstrictors; meperidine; dextromethorphan; cheese or other foods with a high tyramine content; or excessive quantities of caffeine.

Marplan is contraindicated in patients with:

  • a confirmed or suspected cerebrovascular defect or any patients with cardiovascular disease or confirmed or suspected cerebrovascular defect, hypertension, or history of headache.
  • known hypersensitivity to isocarboxazid.
  • pheochromocytoma, as such tumors secrete pressor substances whose metabolism may be inhibited by Marplan.
  • a history of liver disease, or in those with abnormal liver function tests.
  • severe impairment of renal function.

Contraindicated MAOI-Other Drug Combinations

Other MAOI Inhibitors or With Dibenzazepine-Related Entities

Marplan should not be administered together with, or in close proximity to, other MAO inhibitors or dibenzazepine-related entities. Hypertensive crises, severe convulsive seizures, coma, or circulatory collapse may occur in patients receiving such combinations.

Marplan should not be administered in combination with buproprion hydrochloride and SSRI’s. There have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation and confusion progressing to delirium and coma) in patients receiving fluoxetine in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Marplan should not be used with buspirone HCL due to several cases of elevated blood pressure when given together.

Serious reactions may also occur when MAO inhibitors are given with seratoninergic drugs (e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertaline, citalopram and venlafaxine). Marplan should not be administered in combination with sympathomimetics, including amphetimines, or with over-the-counter drugs such as cold, hay fever, or weight-reducing preparations that contain vasoconstrictors. Use of these products with Marplan may precipitate hypertension, headache and related symptoms. The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurologic symptoms, including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillations, and Babinski signs. Meperidine should not be used concomitantly with MAO inhibitors or within 2 or 3 weeks following MAO therapy. Serious reactions have been precipitated with concomitant use, including coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse and death. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. For additional information on the use of Marplan with other drug combinations, please refer to Contraindicated MAOI-Other Drug Combinations section of the full prescribing information.

Cheese or Other Foods With a High Tyramine Content

Hypertensive crises have sometimes occurred during Marplan therapy after ingestion of foods with a high tyramine content. In general, patients should avoid protein foods in which aging or protein breakdown is used to increase flavor. In particular, patients should be instructed not to take foods such as cheese (particularly strong or aged varieties), sour cream, Chianti wine, sherry, beer (including non-alcoholic beer), liqueurs, pickled herring, anchovies, caviar, liver, canned figs, raisins, bananas or avocados (particularly if overripe), chocolate, soy sauce, sauerkraut, the pods of broad beans (fava beans), yeast extracts, yogurt, meat extracts, meat prepared with tenderizers, or dry sausage.

Anesthetic Agents

Patients taking Marplan should not undergo elective surgery requiring general anesthesia. They should not be given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of Marplan and spinal anesthesia should be kept in mind.

Hypertensive Crises

The most important reaction associated with MAOI’s is the occurrence of hypertensive crises, which have sometimes been fatal, resulting from co-administration of MAOI’s and certain drugs and foods. If a hypertensive crisis occurs, Marplan should be discontinued, and therapy to lower blood pressure should be instituted immediately. Patients should be instructed to report promptly the occurrence of headache or other unusual symptoms, i.e., palpitation and/or tachycardia, a sense of constriction in the throat or chest, sweating, dizziness, neck stiffness, nausea, or vomiting. Patients on Marplan therapy should also be told not to drink alcoholic beverages. Patients should be warned about the possibility of hypotension and faintness, as well as drowsiness sufficient to impair performance of potentially hazardous tasks, such as driving a car or operating machinery.


Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults with MDD and other psychiatric disorders in short-term studies. Anyone considering the use of Marplan or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.

Marplan is not approved for use in pediatric patients.

Families and caregivers should be advised of the need for close observation and communication with the prescriber. Marplan is not approved for treating bipolar depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

It is unknown whether the suicidality risk extends to longer–term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

Screening Patients for Bipolar Disorder

Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

WARNINGS: Second Line Status

Marplan is not recommended as initial therapy but should be reserved for patients who have not responded satisfactorily to other antidepressants.

Hypertensive Crises

The most important reaction associated with MAO inhibitors is the occurrence of hypertensive crises, which have sometimes been fatal, resulting from the co-administration of MAOIs and certain drugs and foods.

Therapy should be discontinued immediately if palpitations or frequent headaches occur during Marplan therapy as these symptoms may be prodromal of a hypertensive crisis.

If a hypertensive crisis occurs, Marplan should be discontinued, and therapy to lower blood pressure should be instituted immediately.

Limited Experience With Marplan at Higher Doses

Because of the limited experience with systematically monitored patients receiving Marplan at the higher end of the currently recommended dose range of up to 60 mg/day, caution is indicated in patients for whom a dose of 40 mg/day is exceeded.


Hypotension has been observed during Marplan therapy. Symptoms of postural hypotension are seen most commonly, but not exclusively, in patients with preexistent hypertension; blood pressure usually returns rapidly to pretreatment levels upon discontinuation of the drug. Dosage increases should be made more gradually in patients showing a tendency toward hypotension at the beginning of therapy.

Lower Seizure Threshold

Because Marplan lowers the convulsive threshold in some animal experiments, suitable precautions should be taken if epileptic patients are treated.


There is a low incidence of altered liver function or jaundice in patients treated with Marplan.

Important Safety Information

Long-term studies to evaluate carcinogenic potential have not been conducted in this drug, and there is no information concerning mutagenesis or impairment of fertility.

The potential reproductive toxicity of isocarboxazid has not been adequately evaluated in animals. It is also not known whether isocarboxazid can cause embryo/fetal harm when administered to a pregnant woman or can affect reproductive capacity. Marplan should be given to a pregnant woman only if clearly needed.

Levels of excretion of isocarboxazid and/or its metabolites in human milk have not been determined, and effects on the nursing infant are unknown. Marplan should be used in women who are nursing only if clearly needed. Physicians should carefully evaluate Marplan patients for history of drug abuse (e.g., development of tolerance, increments of dose, drug-seeking behavior).

Pediatric Use-Safety and effectiveness in the pediatric population have not been established.


Seek emergency medical attention or call the Poison Help Line at 1-800-222-1222.


Adverse Findings Observed in Short-Term, Placebo-Controlled Trials

The commonly observed adverse event that occurred in Marplan patients with an incidence of 5% or greater and at least twice the incidence in placebo patients were nausea, dry mouth, and dizziness.

Call your doctor for medical advice about any side effects you may experience. You may report side effects to Validus Pharmaceuticals LLC at 1-866-982-5438.

Important Safety Information for Patients10

Side Effects, Dietary Considerations, and Drug Interactions to Consider When Taking Marplan® (isocarboxazid) Tablets

Because Marplan® (isocarboxazid) Tablets work differently, you’ll be asked to take them in a different way than the other medications for depression.

  • You’ll be asked to stop taking your current medication for at least 2 weeks prior to initiating Marplan. During this period, your physician will monitor you closely. If you experience any symptoms, contact him or her immediately.
  • Please be mindful that Marplan may interact with some other prescription medicines, some OTC cough/cold, weight-control, and hay fever/allergy preparations, and some herbal supplements and may cause adverse events. Be sure to tell your doctor about all the medications and supplements you are taking.
  • When taking Marplan therapy, you need to avoid certain foods that might interact with its MAO inhibitor effects. Some foods may be high in a chemical called tyramine. Although you’ll need to avoid any foods that have a high tyramine level, you can enjoy a considerable variety of fresh foods and pasteurized foods.
  • You should not consume alcoholic beverages while taking Marplan.

Click here to download a handy Dietary Guide that lists these foods for you

Here is a brief list of “Do’s and Don’t’s” to help you take Marplan correctly. Following these instructions will reduce your likelihood of experiencing any untoward effects and increase your likelihood for success with Marplan therapy:


  • Consult with your physician or other healthcare elsewhere professionals about the benefits and risks of using Marplan and how to take it appropriately.
  • Promptly tell your doctor if you experience any of the following symptoms while using Marplan:
    • headache
    • palpitations/tachycardia (rapid heart beat)
    • sense of constriction in the throat or chest
    • dizziness
    • neck stiffness
    • nausea or vomiting
  • Be vigilant for changes in behavior while using Marplan, especially when you are beginning Marplan therapy, or when the dose of Marplan is being changed. These changes in behavior may indicate a worsening of your depression and an increased risk of suicide. On a day-to-day basis, patients and their families and caregivers should be alert to the emergence of an increase in symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsive behavior, akathisia (inner restlessness), mania, hypomania (a mind in persistent overdrive), worsening of depression, and thoughts of suicide.
  • Report any of these symptoms to the doctor, especially if they were not part of your initial symptoms, and if they are severe or abrupt in onset.
  • Be aware that Marplan may cause drowsiness, hypotension, and faintness. If these symptoms occur, you should not perform potentially dangerous tasks, such as driving or operating machinery.
  • Inform other healthcare professionals who are providing you with care (other doctors, the dentist, and other health professionals) that you are taking Marplan.


  • Don’t eat certain foods containing tyramine while taking Marplan. Tyramine may interact with Marplan to cause serious untoward effects. Click here to view and download a helpful Dietary Guide that lists foods to avoid.
  • Don’t drink alcoholic beverages.
  • Don’t take additional prescription medicines or over-the-counter drugs without first consulting with your doctor or pharmacist. Some OTC cough/cold, weight-control, and hay fever/allergy preparations may interact with Marplan to cause serious effects.
  • Don’t consume excessive amounts of caffeine. Caffeine is found in such products as coffee, tea, chocolate, cola drinks, and OTC “stay-awake” drugs. See the Dietary Guide for limits in the amount of these beverages you can consume.

Always discuss the results of your Marplan therapy with your doctor. A few foods can cause dangerous interactions with Marplan – but most of the foods that you like may be just fine to eat. Here’s information about

  • Why food interactions can happen
  • The new information about the many foods you can enjoy
  • The few foods and beverages to avoid

The Cause of Food Interactions8

In the gut, MAO Inhibitors can cause an increase in levels of a chemical called tyramine. Tyramine is also present in some foods and beverages, particularly when those foods and beverages are aged or fermented.

If there is too much tyramine in the body, a dangerous rise in blood pressure that may be potentially fatal, may occur (hypertensive crisis). That’s why it is important that you minimize the tyramine you consume while you are taking Marplan.

Years ago, when Marplan was first introduced, nutritionists didn’t have advanced ways to measure tyramine in foods and beverages. So, to be as safe as possible, a diet restricting foods containing tyramine was developed; but that old diet was difficult to stay with because so many foods were incorrectly thought to be “off limits.”

Fortunately—based on newer scientific studies—the recommendations have changed. While there still are some foods and drinks you should avoid—or consume only in moderation, we now know that most foods that were once restricted are, in fact, very low in tyramine—and considered safe to consume when you are taking Marplan.

However, you’ll want to avoid any aged cheeses, fermented/dry/aged meats such as salami, most soy products, or any foods that haven’t been stored properly or have passed their expiration dates.

Don’t drink alcoholic beverages, especially those containing high amounts of tyramine (including white wine and tap beer). As with all antidepressants, it is unwise to drink any alcohol since it may aggravate the symptoms of depression.

More information can be obtained from other on-line resources listed on this website or from your doctor.

The Good News About the Many Foods You Can Enjoy

The most contemporary diet guidance indicates that you can take Marplan while enjoying many of the foods and beverages that you currently like. Look below at the “Menu for a New Beginning” and you’ll see that freshness is the key – fresh dairy, fresh poultry, fresh fish, and fresh packaged or processed meats are safe food choices when you are taking Marplan. So, go right ahead and enjoy a burger or a hot dog at the barbecue. Nearly all fruits and vegetables are OK too.

Marplan Foods

Avoiding Medication Interactions While Taking Marplan® (isocarboxazid) Tablets10

Some medications can interact with Marplan® (isocarboxazid) Tablets and cause unwanted effects. To avoid these effects, be sure to tell your doctor about ALL of the other medications you are taking, including herbal supplements.

Here is a list of medication combinations that should be avoided:

  • Marplan should be administered with caution to patients receiving Antabuse (disulfiram).
  • The use of Marplan in combination with other psychotropic agents is not recommended without your doctor’s knowledge, because one product can potentially magnify the effects of the other.
  • The MAO inhibiting effects of Marplan can persist for a substantial period after it has been discontinued, so it is best to wait at least 10 days before taking any other psychotropic medication.
  • Marplan should not be used with other MAO inhibitors, tri-cyclic medications (dibenzazepine-related and other); Wellbutrin (buproprion); SSRI antidepressants; Buspar (buspirone); sympathomimetic drugs including amphetamines and over-the-counter cold, hay fever or weight-reducing preparations containing vasoconstrictors (decongestants); tryptophan; Demerol (meperidine); the cough-preventative dextromethorphan; anesthetic agents; blood pressure drugs, including thiazide diuretics; excessive amounts of caffeine; or central nervous system depressants such as narcotics, barbiturates, and alcohol. For a complete list of drugs to avoid please see “CONTRAINDICATIONS” in the important safety information and the full prescribing information.

Please click here to review the Marplan references.