Isocarboxazid

Mechanism-of-action classes: Monoamine Oxidase Inhibitors; Serotonin Uptake Inhibitors.

• Marplan is indicated for the treatment of depression. Because of its potentially serious side effects, Marplan is not an antidepressant of first choice in the treatment of newly diagnosed depressed patients.

• Marplan (isocarboxazid) should not be administered in combination with any of the following: MAO inhibitors or dibenzazepine derivatives; sympathomimetics (including amphetamines); some central nervous system depressants (including narcotics and alcohol); antihypertensive, diuretic, antihistaminic, sedative or anesthetic drugs, buproprion HCL, buspirone HCL, dextromethorphan, cheese or other foods with a high tyramine content; or excessive quantities of caffeine. Marplan (isocarboxazid) should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease, hypertension, or history of headache.contraindicated

For maximum therapeutic effect, the dosage of Marplan must be individually adjusted on the basis of careful observation of the patient. Dosage should be started with one tablet (10 mg) of Marplan twice daily. If tolerated, dosage may be increased by increments of one tablet (10 mg) every 2 to 4 days to achieve a dosage of four tablets daily (40 mg) by the end of the first week of treatment. Dosage can then be increased by increments of up to 20 mg/week, if needed and tolerated, to a maximum recommended dosage of 60 mg/day. Daily dosage should be divided into two to four dosages. After maximum clinical response is achieved, an attempt should be made to reduce the dosage slowly over a period of several weeks without jeopardizing the therapeutic response. Beneficial effect may not be seen in some patients for 3 to 6 weeks. If no response is obtained by then, continued administration is unlikely to help. 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 (see ADVERSE REACTIONS ).

TO PHYSICIANS 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. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. 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 with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials of nine antidepressant drugs (SSRIs) and others) in children and adolescents with MDD, Obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials Systematically collected data are available from only 86 patients exposed to Marplan, of whom only 52 received doses of ≥50 mg/day, including only 11 who were dosed at ≥60 mg/day. 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 ( see WARNINGS ). The table that follows enumerates the incidence, rounded to the nearest percent, of treatment emergent adverse events that occurred among 86 depressed patients who received Marplan at doses ranging from 20 to 80 mg/day in placebo-controlled trials of 6 weeks in duration. Events included are those occurring in 1% or more of patients treated with Marplan and for which the incidence in patients treated with Marplan was greater than the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators.

Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressant, including MARPLAN, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants 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.

Metabolism

Marplan pharmacokinetic information is not available.

The lethal dose of Marplan in humans is not known. There has been one report of a fatality in a patient who ingested 400 mg of Marplan together with an unspecified amount of another drug. Symptoms: Major overdosage may be evidenced by tachycardia, hypotension, coma, convulsions, respiratory depression, sluggish reflexes, pyrexia, and diaphoresis; these signs may persist for 8 to 14 days. Treatment: General supportive measures should be used, along with immediate gastric lavage or emetics. If the latter are given, the danger of aspiration must be borne in mind. An adequate airway should be maintained, with supplemental oxygen if necessary. The mechanism by which amine-oxidase inhibitors produce hypotension is not fully understood, but there is evidence that these agents block the vascular bed response. Thus it is suggested that plasma may be of value in the management of this hypotension. Administration of pressor amines such as Levophed ® (levarterenol bitartrate) may be of limited value (note that their effects may be potentiated by Marplan). Continue treatment for several days until homeostasis is restored.

• Jul 1, 1959NDANDA011961Lifsa Drugs

Reference statistics from the openFDA drug-shortage dataset. For a live view, consult the FDA database directly. Not clinical guidance.

• Marplan, Tablet, 10 mg, 100 count bottle (NDC 72336-032-01)Active
  Sponsor: Lifsa Drugs LLC
  Updated Jun 3, 2026

1. 1Completed Suicide1622%
2. 2Insomnia811%
3. 3Toxicity To Various Agents811%
4. 4Drug Ineffective79.7%
5. 5Serotonin Syndrome68.3%
6. 6Stress Cardiomyopathy68.3%
7. 7Dizziness56.9%
8. 8Vision Blurred56.9%
9. 9Blood Pressure Increased45.6%
10. 10Confusional State45.6%
11. 11Depression45.6%
12. 12Hyperhidrosis45.6%
13. 13Malaise45.6%
14. 14Muscle Twitching45.6%
15. 15Diarrhoea34.2%

Recent PubMed references pinned to Isocarboxazid as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Treatment History Characteristics Associated With Use of Isocarboxazid: A Nationwide Register-Based Study.
  Journal of clinical psychopharmacology · 2022 · Holm M, Larsen JK, Ishtiak-Ahmed K, et al.
  PMID 35067519DOI 10.1097/JCP.0000000000001505
• [The use of the monoamine oxidase inhibitor isocarboxazide in treatment-resistant depression].
  Ugeskrift for laeger · 2015 · Larsen JK, Krogh-Nielsen L, Brøsen K, et al.
  PMID 26692222
• Vitamin B6 treatment of oedema induced by mirtazapine and isocarboxazid.
  Acta psychiatrica Scandinavica · 2011 · Larsen JK, Bendsen BB, Bech P, et al.
  PMID 21410439DOI 10.1111/j.1600-0447.2011.01695.x
• [Prolonged hyperthermia after isocarboxazid poisoning].
  Ugeskrift for laeger · 2003 · Ellervik C, Høgholm A
  PMID 12772401
• The reappearance of a monamine oxidase inhibitor (isocarboxazid).
  Journal of clinical psychopharmacology · 1999 · Shader RI, Greenblatt DJ
  PMID 10211910DOI 10.1097/00004714-199904000-00001
• Toxic interaction of venlafaxine and isocarboxazide.
  Lancet (London, England) · 1995 · Klysner R, Larsen JK, Sørensen P, et al.
  PMID 7475741DOI 10.1016/s0140-6736(95)91900-7
• A 3-year follow-up of a group of treatment-resistant depressed patients with a MAOI/tricyclic combination.
  Journal of affective disorders · 1995 · Berlanga C, Ortega-Soto HA
  PMID 7560546DOI 10.1016/0165-0327(95)00016-g
• Response to "Sertraline and isocarboxazid cause a serotonin syndrome".
  Journal of clinical psychopharmacology · 1995 · Kirrane R, Bodner R, Lynch T, et al.
  PMID 7782491DOI 10.1097/00004714-199504000-00014

The 2 most recently updated of 2 ClinicalTrials.gov registrations naming Isocarboxazid as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers
  Completed · Early phase 1 · Interventional · 20 enrolled · Imperial College London
  NCT02323217updated 2021-11-15
• Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
  Completed · Phase 4 · Interventional · 27 enrolled · University of Ottawa
  NCT00704860updated 2011-01-19

Frequently asked questions

How does Isocarboxazid work?

Mechanism-of-action classes: Monoamine Oxidase Inhibitors; Serotonin Uptake Inhibitors.

What is Isocarboxazid used for?

According to FDA labeling, Isocarboxazid carries indications including: Marplan is indicated for the treatment of depression. Because of its potentially serious side effects, Marplan is not an antidepressant of first choice in the treatment of newly diagnosed depressed patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Isocarboxazid?

Isocarboxazid is classified as Monoamine oxidase inhibitors, non-selective, Monoamine Oxidase Inhibitor, Monoamine Oxidase Inhibitors, Serotonin Uptake Inhibitors, Increased Norepinephrine Activity, Increased Serotonin Activity, Vasoconstriction.

What are the brand names for Isocarboxazid?

Isocarboxazid is marketed under brand names including Marplan.

What are the contraindications for Isocarboxazid?

Isocarboxazid labeling lists contraindications including: Marplan (isocarboxazid) should not be administered in combination with any of the following: MAO inhibitors or dibenzazepine derivatives; sympathomimetics (including amphetamines); some central nervous system depressants (including narcotics and alcohol); antihypertensive, diuretic, antihistaminic, sedative or anesthetic drugs, buproprion HCL, buspirone HCL, dextromethorphan, cheese or other foods with a high tyramine content; or excessive quantities of caffeine. Marplan (isocarboxazid) should not be administered to any patient with a confirmed or suspected cerebrovascular defect or to any patient with cardiovascular disease, hypertension, or history of headache.. Always consult the full prescribing information and a clinician.