Isocarboxazid - Mechanism of Action, Indications, Dosage, and Adverse Drug Reactions

Overview:

Isocarboxazid is a monoamine oxidase inhibitor. The chemical formula for Isocarboxazid is 1-benzyl-2-(5-methyl-3-isoxazolyl carbonyl) hydrazine-isocarboxazid. It is used to treat serious depression, dysthymic disorder, atypical disorders, panic disorder, and phobias. It was approved by the FDA as a prescription medicine on July 1, 1959, for the treatment of depression.

How Does the Drug Work?

Isocarboxazid works by suppressing the action of monoamine oxidases (MAO) in the nervous system in an irreversible manner. MAO subtypes A and B are involved in the breakdown of serotonin and catecholamine neurotransmitters like adrenaline, norepinephrine, and dopamine. As a nonselective MAO inhibitor, Isocarboxazid binds irreversibly to monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Isocarboxazid reduces MAO activity, which causes a rise in serotonin, epinephrine, norepinephrine, and dopamine concentrations in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The antidepressant action of MAO inhibitors such as Isocarboxazid is based on an increase in one or more monoamines.

Indications:

• Isocarboxazid is a medication used to treat depression. Depression is a common yet dangerous mental illness. The patient's moods, thoughts, and capacity to handle daily activities will alter. The signs of a mood illness must be present for at least two consecutive weeks for it to be termed depression.

• Isocarboxazid is not an antidepressant of first choice for the management of recently diagnosed patients with depression, due to its potentially dangerous adverse effects.

• Isocarboxazid is a prescription drug used to treat major depression in patients who have not reacted well to previous antidepressant treatments. Isocarboxazid inhibits certain enzymes, causing an increase in various substances like monoamines that reverse depression in the brain.

Contraindications:

• Isocarboxazid is not recommended for use in patients who have a history of hypersensitivity to the drug.

• Isocarboxazid should not be given to anyone with a confirmed or suspected cerebrovascular defect, as well as anyone with cardiovascular disease, hypertension, or a history of headaches.

• Isocarboxazid should not be taken in the presence of pheochromocytoma because these tumors release pressor chemicals, whose metabolism Isocarboxazid may hinder.

• Patients with a history of liver illness or abnormal liver function tests should not be given Isocarboxazid.

• Isocarboxazid should not be used in people with severe renal impairment.

• Isocarboxazid should not be taken in patients who consume cheese or other foods high in tyramine or excessive amounts of caffeine.

• Isocarboxazid is not recommended for use in patients under medications for depression, other MAO inhibitors, drugs with active ingredients such as Adrenaline, Amphetamine, Fenfluramine, Dopamine, or Ephedrine, drugs containing ingredients such as Carbamazepine, Bupropion, or Buspirone, taking strong painkillers like Pethidine and drugs containing ingredients such as Sumatriptan, Almotriptan, Rizatriptan, Naratriptan, Zolmitriptan or Eletriptan.

How Is Isocarboxazid Administered?

Isocarboxazid dosage must be specifically adjusted based on careful patient observation for the best therapeutic benefit. Isocarboxazid dosage should be begun orally with one tablet (10 mg) twice daily. If accepted, the dosage may be increased by one tablet (10 mg) every two to four days until it reaches four tablets daily (40 mg) by the end of the first seven days of treatment. If required and accepted, the dose can subsequently be raised by increments of up to 20 mg/week to a maximum suggested dosage of 60 mg/day. The daily intake should be split into two to four doses. After achieving optimum clinical response, an attempt should be made to gradually reduce the dosage over the course of several weeks without compromising the therapeutic response. Some patients may not see a benefit for three to six weeks. If no response is received by that time, further administration may not be beneficial. Because of the insufficient experience with carefully observed individuals receiving Isocarboxazid at the higher end of the currently suggested dose range of up to 60 mg/day, patients who exceed a dose of 40 mg/day need to be cautious.

Dosage Forms and Strengths:

Isocarboxazid is available in 10 mg (milligram) oral tablet form.

Warnings and Precautions:

The warnings and precautions associated are as follows:

• It is critical that the doctor monitor the progress on a frequent basis to allow for modifications in the dosage and to look for any side effects.

• The patient will also need to have their blood pressure checked before and during taking this medication. Call the doctor right away if any changes in the normal blood pressure. Consult the doctor if any doubts.

Isocarboxazid can induce potentially severe responses when combined with certain meals, drinks, or other medications, such as rapid high blood pressure (also known as a hypertensive crisis). To avoid such responses, use the following precautions:

• Avoid foods high in dopamine and tyramine, such as cheese (especially strong or old versions), caviar, sour cream, liver, canned figs, soy sauce, fermented cabbage, fava beans, yeasts, and curd. Smoked or pickled meat, poultry, or fish, such as sausage, pepperoni, salami, anchovies, or herring, should be avoided. Dried fruit (such as raisins), bananas, avocados, raspberries, and overripe fruit should be avoided.

• Consuming alcoholic beverages like Chianti wine, sherry, beer, non-alcohol or low-alcohol beer and wine, or liquors should be avoided.

• Caffeine should not be consumed in excess. Caffeine is found in coffee, cola, chocolate, tea, and a variety of other foods and beverages. Consult the doctor to determine how much caffeine is safe to consume.

Isocarboxazid may produce agitation, irritability, or other aberrant behaviors in some people. Some people may experience suicidal thoughts and urges, as well as an increase in depression. If observe any of these side effects, contact the doctor immediately.

• If people develop a severe headache, stiff neck, chest pain, fast heartbeat, sweating, dizziness, nausea, or vomiting while taking this drug, contact the doctor immediately or go to the nearest hospital emergency room. These could be symptoms of a significant adverse reaction known as a hypertensive crisis.

• Some people may become dizzy or are less aware as a result of this medication. Before driving, running machinery, or doing anything else that could be risky if one becomes dizzy or is not alert, make sure to know how the body will react to this drug. This medication will amplify the effects of alcohol and other CNS depressants (medications that cause drowsiness or make people less attentive). Antihistamines or drugs for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping drugs; pain relievers or narcotics; drugs for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics, are examples of CNS depressants. Consult the doctor before taking any of the above drugs while taking this medication.

• Do not discontinue using this medication unless consult with a physician. The physician may advise to gradually reduce the quantity one uses before discontinuing it entirely.

• Tell the doctor or dentist if one is using this medicine or has taken it within the last 10 days before undergoing any type of surgery, dental treatment, or emergency care. When isocarboxazid is used with medications used during surgery, dentistry, or emergency procedures, the risk of major adverse effects increases.

• If people experience any symptoms of liver disease, such as dark urine or pale stools, nausea, vomiting, lack of appetite, pain in the upper stomach, or yellowing of their skin or the whites of their eyes, consult the doctor immediately.

• This medication may have an effect on blood sugar levels. If people have diabetes, then should be extra cautious when checking for sugar in their blood or urine.

• People must avoid eating certain foods, drinks, and other medications for at least two weeks after stopping this drug since these products may continue to react with Isocarboxazid.

Adverse Reactions:

Isocarboxazid, like all medications, can produce side effects, though not everyone experiences it.

Serious Side Effects:

• Severe blood alterations (inadequate red and white blood cells and platelets) with symptoms such as overall discomfort, bleeding, skin bleeding and mucous membrane bleeding, bruises, and a tendency for inflammation (infections), particularly throat and fever.

• Suicide-related thoughts or behaviors.

• Hypertensive crisis.

• Serotonin syndrome (a potentially deadly drug-induced condition characterized by an excess of serotonin in the brain's synapses).

• Orthostatic hypotension (a sudden decrease in blood pressure while rising from a seated or lying down position).

Non-serious Side Effects:

• Common Side Effects

  • Rapid heart rate. It may be serious. Consult a doctor or an emergency hospital if people have a very fast or irregular pulse, become ill, or fail.

  • Dizziness, sleepiness, and fainting after changing positions from resting to sitting or sitting to standing due to low blood pressure.

  • Blurred vision.

  • Nausea, vomiting, and constipation.

  • Elevated feet, ankles, and hands, as well as weakness and weariness.

  • Unable to sleep.

• Unusual Side Effects

  • Urine passage difficulties. It has the potential to have a significant adverse effect. Consult the doctor.

  • Weight gain.

  • Excessive perspiration.

  • Erection and ejaculation inhibition.

  • Agitation, turbulence, and confusion.

  • Quick reflexes, muscle disturbances, and shaking.

  • Tingling, spinning feelings, numbness or paralysis, and even hand and foot discomfort.

  • Migraine.

  • High blood pressure.

For Patients

Why Is Isocarboxazid Prescribed?

Isocarboxazid is prescribed for the treatment of depression in people who have not responded to other antidepressants. Isocarboxazid belongs to a class of drugs known as monoamine oxidase (MAO) inhibitors. It works by increasing the amounts of certain natural chemicals in the brain, which aid in the maintenance of mental balance.

How Should Isocarboxazid Be Used?

• Isocarboxazid is a tablet taken by mouth two to four times a day. It is critical to follow the prescription instructions and visit a doctor or pharmacist if any doubts arise.

• The tablets should be swallowed with water or liquid, or crumbled and swallowed with food or beverage.

• As Isocarboxazid has the potential to become habit-forming, it should not be taken in greater doses, more frequently, or for longer than advised.

• Doctors typically begin with a low dose and progressively raise it before gradually decreasing it if symptoms improve.

• Isocarboxazid is used to treat, but not cure, depression. It could take three to six weeks or more to experience the full benefits.

• Continue taking Isocarboxazid if symptoms do not improve during the first six weeks.

• Do not discontinue taking Isocarboxazid without consulting with the doctor.

What Special Precautions Should Be Taken?

• Patients should notify their doctor and pharmacist if patients are allergic to Isocarboxazid, any other drugs, or any of the inactive substances in Isocarboxazid tablets.

• If patients are taking or plan to take any antidepressants, amphetamines, antihistamines, barbiturates, Bupropion, Buspirone, caffeine, Cyclobenzaprine, Dextromethorphan, diuretics, Duloxetine, Ephedrine, Epinephrine, Guanethidine, Levodopa, medications for allergies, asthma, cough, cold symptoms, high blood pressure, mental illness, Inform the doctor about any other drugs, vitamins, or herbal supplements that the patient is now using or intends to use.

• Isocarboxazid may persist in the body for up to two weeks after discontinuation, so consult the doctor before beginning any new medications.

• Isocarboxazid may cause drowsiness in patients, so avoid driving, operating machinery, climbing ladders, or working in high locations.

• Do not consume alcohol while taking Isocarboxazid since it may cause drowsiness.

• If patients feel dizziness, lightheadedness, or fainting when rising from a lying posture too rapidly, rise out of bed carefully and place their feet on the floor before standing up.

• Consuming high-tyramine foods such as smoked meat, aged cheese, rotten fruits and vegetables, legumes, alcoholic beverages, and fermented yeast products during Isocarboxazid treatment can result in a serious reaction. For precise limitations, consult a doctor or a dietician, and avoid caffeine-containing foods and beverages.

Side Effects:

Common side effects of Isocarboxazid include:

• Dry mouth.

• Constipation.

• Diarrhea.

• Weakness.

• Excessive weariness.

• Forgetfulness.

• Reduced sexual capacity.

• Frequent, painful, or problematic urination.

Serious Side Effects:

• Headaches.

• Chest pain.

• Sweating.

• Fever.

• Chills.

• Cold and clammy skin.

• Dizziness.

• Chest or throat tightness.

• Stiff neck.

• Nausea.

• Vomiting.

• Fainting.

• Blurred vision.

• Light sensitivity.

• Wide pupils.

• Yellowing skin or eyes.

• Uncontrollable shaking.

• Sudden jerking.

• Seizures.

• Feelings of numbness, burning, or tingling in the arms or legs.

If patients have any odd issues while taking this medicine, contact the doctor immediately.

Storage of Isocarboxazid:

Keep this drug in the packaging it came in, properly closed, and out of the reach of children. Keep it at ambient temperature and away from extreme heat and moisture.

What Can Be Done in the Event of an Overdose?

In the case of an overdose, call emergency services or a poison control center immediately if the patient has experienced overdose symptoms. Overdose symptoms may include

• Rapid heartbeat.

• Dizziness.

• Fainting.

• Blurred vision.

• Nausea.

• Coma (loss of consciousness over an extended period of time).

• Seizures.

• Decreased breathing.

• Weak reflexes.

• Fever.

• Sweating.

For Doctors:

Clinical Trials:

Isocarboxazid's efficacy was proven in two 6-week placebo-controlled studies in adult outpatients with depression-related symptoms fitting the DSM-IV diagnosis of major depressive disorder. Anxiety symptoms (anxious mood, panic, and/or phobic symptoms) were frequently present in the patients. Patients were started on 10 mg daily and gradually increased every two to four days, as permitted, until a therapeutic effect was seen, up to a maximum dose of 80 mg/day. Doses were given on a specific schedule, ranging from two to four times each day. The average dose for each study was around 40 mg/day, with a few individuals receiving doses higher than 60 mg/day. In both studies, patients receiving isocarboxazid had a significantly larger reduction in signs and symptoms related to depression as measured by the Hamilton Depression Scale at the end of 6 weeks, for both the Total Score and the Depressed Mood Score, than patients receiving a placebo.

Pharmacology:

Pharmacodynamics: In vivo and in vitro studies revealed that Isocarboxazid inhibited MAO in the brain, heart, and liver. Isocarboxazid reduces MAO activity, which causes a rise in serotonin, epinephrine, norepinephrine, and dopamine concentrations in storage areas all over the central nervous system (CNS) and sympathetic nervous system. The antidepressant action of MAO inhibitors such as Isocarboxazid is based on a rise in one or more monoamines.

Mechanism of Action:

Isocarboxazid is a drug that operates by suppressing the action of monoamine oxidases (MAO) in the nervous system in an irreversible manner. MAO enzymes are known for their ability to degrade neurotransmitters like serotonin, adrenaline, norepinephrine, and dopamine. Isocarboxazid raises the levels of these neurotransmitters in the brain by inhibiting MAO, which may aid in the treatment of depression.

Half-Life in Adults: 1.5 to two hours. This drug has a very short half-life as it is metabolized rapidly in the liver.

Pharmacokinetics:Although the pharmacokinetic profile of Isocarboxazid has not been thoroughly explored, it is believed that its features will be similar to those of Phenelzine and Tranylcypromine.

Absorption: These drugs are easily absorbed by the gastrointestinal tract, have a low bioavailability, reach their peak levels in one to two hours, and have a high level of protein binding.

Metabolism: These drugs are rapidly metabolized in the liver through the acetylation process. Hippuric acid is an important metabolite in metabolism.

Excretion: The majority of the amount is removed in the urine, accounting for 42.5 percent of the dosage given after 24 hours. 75 percent of the drug that is removed through the kidney is in the form of hippuric acid. After 24 hours, another portion of the eliminated dose is noticed through the intestinal tract, accounting for 22 percent of the given dose.

Drug Interactions:

Some drugs are not to be taken simultaneously in order to avoid interactions; however, in some situations, these drugs can be given by modifying the dose or taking the necessary precautions.

It is not advised to use Isocarboxazid with the following drugs:

• Other MAO Inhibitors like Furazolidone, Pargyline, Methyclothiazide, Phenelzine sulfate, Procarbazine, and Tranylcypromine sulfate.

• Dibenzazepine-Related and Other Tricyclics include Amitriptyline, Perphenazine, Clomipramine hydrochloride, Desipramine, Imipramine, Nortriptyline, Protriptyline, Doxepin, Carbamazepine, Cyclobenzaprine, Amoxapine, Maprotiline, and Trimipramine maleate.

• Buproprion.

• Buspirone.

• Selective Serotonin Reuptake Inhibitors (SSRIs).

• Sympathomimetics.

• Meperidine.

• Dextromethorphan.

• Tyramine-rich foods.

• Excessive quantities of caffeine.

• Anesthetic agents.

• CNS depressants.

• Anti-Hypertensive drugs.

Conclusion:

Isocarboxazid has been proven to be an effective and safe medication for patients with depression and anxiety who are not melancholy or psychotic. Isocarboxazid is an antidepressant that works by increasing the amounts of some naturally occurring substances in the brain. It is used to treat depression and anxiety when other treatments have failed.