indication

May be used to treat major depressive disorder.

pharmacology

Isocarboxazid is a non-selective hydrazine monoamine oxidase (MAO) inhibitor used to treat depression. In vivo and in vitro studies demonstrated inhibition of MAO in the brain, heart, and liver. Depression is a complicated disease that is not fully understood. It is thought that depression may be linked to an imbalance of chemicals within the brain. When depression occurs, there may be a decrease in the amount of chemicals released from nerve cells in the brain. These chemicals are called monoamines. Monoamines are broken down by a chemical called monoamine oxidase. Isocarboxazid prevents monoamine oxidase from breaking down the monoamines. This results in an increased amount of active monoamines in the brain. By increasing the amount of monoamines in the brain, the imbalance of chemicals thought to be caused by depression is altered. This helps relieve the symptoms of depression.

mechanism of action

Isocarboxazid works by irreversibly blocking the action of a chemical substance known as monoamine oxidase (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase–A (MAO-A) and monoamine oxidase–B (MAO-B). The reduced MAO activity results in an increased concentration of these neurotransmitters in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. This increased availability of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors.

toxicity

Signs of overdose include severe anxiety, confusion, convulsions, cool clammy skin, severe dizziness, severe drowsiness, fast and irregular pulse, fever, hallucinations, severe headache, high or low blood pressure, hyperactive reflexes, muscle stiffness, respiratory depression or failure, slowed reflexes, sweating, severe trouble in sleeping, and unusual irritability.

biotransformation

Hepatic and rapid (by oxidation).

absorption

Well absorbed from the gastrointestinal tract.

drug interactions

Almotriptan: The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.

Altretamine: Risk of severe hypotension

Amitriptyline: Possibility of severe adverse effects

Amoxapine: Possibility of severe adverse effects

Amphetamine: Possible hypertensive crisis

Atomoxetine: Possible severe adverse reaction with this combination

Benzphetamine: MAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.

Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like isocarboxazid.

Brimonidine: MAO Inhibitors like isocarboxazid may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.

Buprenorphine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like isocarboxazid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Bupropion: Possible severe adverse reaction with this combination

Buspirone: Possible blood pressure elevation

Citalopram: Possible severe adverse reaction with this combination

Clomipramine: Possibility of severe adverse effects

Desipramine: Possibility of severe adverse effects

Desvenlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Dexfenfluramine: Risk of hypertensive crisis.

Dextroamphetamine: Possible hypertensive crisis

Dextromethorphan: Possible severe adverse reaction

Diethylpropion: Possible hypertensive crisis

Dobutamine: Increased arterial pressure

Donepezil: Possible antagonism of action

Dopamine: Increased arterial pressure

Doxepin: Possibility of severe adverse effects

Duloxetine: Possible severe adverse reaction with this combination

Entacapone: Possible hypertensive crisis with this combination

Ephedra: Increased arterial pressure

Ephedrine: Increased arterial pressure

Epinephrine: Increased arterial pressure

Escitalopram: Possible severe adverse reaction with this combination

Fenfluramine: Possible hypertensive crisis

Fenoterol: Increased arterial pressure

Fluoxetine: Possible severe adverse reaction with this combination

Fluvoxamine: Possible severe adverse reaction with this combination

Galantamine: Possible antagonism of action

Guanethidine: Isocarboxazid may decrease the effect of guanethidine.

Imipramine: Possibility of severe adverse effects

Isoproterenol: Increased arterial pressure

L-Tryptophan: Possible severe adverse reaction with this combination

Levodopa: Possible hypertensive crisis

Mazindol: Possible hypertensive crisis

Meperidine: Potentially fatal adverse effects

Mephentermine: Increased arterial pressure

Metaraminol: Increased arterial pressure

Methamphetamine: Possible hypertensive crisis

Methotrimeprazine: Possible severe adverse reaction with this combination

Methoxamine: Increased arterial pressure

Methylphenidate: Possible hypertensive crisis with this combination

Midodrine: Possible hypertensive crisis with this combination

Mirtazapine: Possible severe adverse reaction with this combination

Naratriptan: The use of two serotonin modulators increases the risk of serotonin syndrome. Consider alternate therapy or monitor for signs and symptoms of serotonin syndrome.

Nefazodone: Possible severe adverse reaction with this combination

Norepinephrine: Increased arterial pressure

Nortriptyline: Possibility of severe adverse effects

Orciprenaline: Increased arterial pressure

Paroxetine: Possible severe adverse reaction with this combination

Phendimetrazine: Possible hypertensive crisis

Phenmetrazine: Possible hypertensive crisis

Phentermine: Possible hypertensive crisis

Phenylephrine: Increased arterial pressure

Phenylpropanolamine: Increased arterial pressure

Pirbuterol: Increased arterial pressure

Procaterol: Increased arterial pressure

Protriptyline: Possibility of severe adverse effects

Pseudoephedrine: Increased arterial pressure

Rivastigmine: Possible antagonism of action

Rizatriptan: The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.

Salbutamol: Increased arterial pressure

Sertraline: Possible severe adverse reaction with this combination

Sibutramine: Possible serotoninergic syndrome with this combination

Sumatriptan: The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, sumatriptan. Concomitant therapy is contraindicated.

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Isocarboxazid, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Terbutaline: Increased arterial pressure

Tetrabenazine: Tetrabenazine may increase the adverse/toxic effects of Isocarboxazid. Concomitant therapy is contraindicated.

Tolcapone: Tolcapone and Isocarboxazid decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.

Tramadol: Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, isocarboxazid.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimethobenzamide: Trimethobenzamide and Isocarboxazid, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Triprolidine: Triprolidine and Isocarboxazid, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Isocarboxazid, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Venlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Vilazodone: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.

Zolmitriptan: The MAO inhibitor, isocarboxazid, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing isocarboxazid are contraindicated.