Nardelzine

Uses

Nardelzine is a monoamine oxidase inhibitor used to treat atypical, nonendogenous, or neurotic depression.

Nardelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy.

Atypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression.

Neurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category.

A nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living.

Nardelzine is also used to associated treatment for these conditions: Exogenous depression, Neurotic depression, Atypical Depressive disorder

How Nardelzine works

The basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Nardelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase.

Toxicity

Nardelzine, as must of the monoamine oxidase inhibitors, can cause transient, mild and asymptomatic aminotransferase elevations. It has also been reported to be associated with cases of liver injury after 1-3 months of treatment.

Food Interaction

• Avoid alcohol.
• Avoid St. John's Wort. Administering phenelzine with St. John's Wort may increase the risk of serotonin syndrome.
• Avoid tyramine-containing foods and supplements. Tyramine-containing foods and beverages can cause a sudden elevation in blood pressure or a hypertensive crisis. Foods that contain tyramine include aged cheese, ripe bananas, red wine, some alcoholic beverages (beer), cured food, pickled food, and fava beans.
• Limit caffeine intake. Excess caffeine intake can also cause a hypertensive crisis.

[Major] CONTRAINDICATED: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs).

The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact.

Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of MAOIs.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor.

These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements.

Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well.

At least 14 days should elapse following discontinuation of MAOI therapy before these foods may be consumed.

Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned.

Patients should be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms.

Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

Nardelzine Drug Interaction

Major: amphetamine / dextroamphetamine, citalopram, duloxetine, fentanyl, escitalopram, fluoxetine, vortioxetine, vilazodoneModerate: contained in alcoholic beverages , lorazepam, suvorexant, diphenhydramine, diltiazem, lithium, quetiapineUnknown: aspirin, omega-3 polyunsaturated fatty acids, acetaminophen, acetaminophen, cholecalciferol

Nardelzine Disease Interaction

Major: blood pressure, carcinoid syndrome, headaches, hyperthyroidism, liver disease, pheochromocytoma, renal dysfunction, alcohol, depression, hypertension/CVD, liver disease, pheochromocytoma, severe renal diseaseModerate: hypoglycemia, parkinsonism, schizophrenia/bipolar, seizures, angina, bipolar disorder screening, diabetes, hypotension, renal disease, schizophrenia, seizures, glaucoma

Volume of Distribution

The volume of distribution of phenelzine is hard to determine as drugs from this kind penetrate the CNS very well into the tissue where their activity is desired.

Elimination Route

Nardelzine is rapidly absorbed from the gastrointestinal tract. The decay of the drug action is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of monoamine oxidase. The mean Cmax is 19.8 ng/ml and it occurs after 43 minutes of dose administration.

Half Life

After administration phenelzine presents a very short half-life of 11.6 hours in humans.

Elimination Route

The elimination of the administered dose is mainly composed of the phenelzine metabolites, phenylacetic acid and parahydroxyphenylacetic acid that constitute 79% of the dose found in the urine in the first 96 hours.

Innovators Monograph

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