Usual Adult Dose for Depression

Early phase treatment:

• Initial dose: 15 mg orally 3 times a day
• Dose titration: Increase to at least 60 mg per day fairly rapidly, as tolerated
• Maximum dose: 90 mg/day

Maintenance:

• Maintenance dose may be as low as 15 mg orally once a day or 15 mg orally every other day
• Duration of therapy: As long as required

Comments:

• This drug should rarely be the first antidepressant used; it is more suitable for patients unresponsive to more commonly used medications.
• This drug is effective in depressed patients characterized as atypical, nonendogenous, or neurotic, who often have mixed anxiety and depression and phobic or hypochondriacal features.
• Evidence of usefulness in severely depressed patients with endogenous features is less conclusive.
• Clinical response may not be seen until at least 4 weeks at 60 mg per day dosing
• After maximal benefit is achieved, reduce dose slowly over several weeks.

Use: Treatment of clinically characterized atypical, nonendogenous, or neurotic depression, especially in patients who have failed first-line treatments

Renal Dose Adjustments

Mild to moderate renal dysfunction: Data not available
Severe renal dysfunction: Contraindicated
Renal disease: Contraindicated

Liver Dose Adjustments

Liver dysfunction: Data not available
Patients with a history of liver disease: Contraindicated
Patients with abnormal liver function tests: Contraindicated

Dose Adjustments

Switching FROM:

• Other MAOIs, other antidepressants (e.g., dibenzazepines/tricyclics, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]), bupropion, or buspirone: At least 10 to 14 days
• High tyramine-content foods: At least 10 to 14 days
• Fluoxetine: Allow at least 5 weeks after stopping fluoxetine and starting this drug.

Use during treatment:

• Antihypertensives: Use with caution.

Adverse reactions occurring during treatment:

• Hypotension/postural hypotension: Dose increases should be avoided. This drug should be discontinued if symptoms are persistent.
• Palpitations and/or unusually frequent headaches: Reduce the dosage; treatment should be discontinued if rapid improvement is not observed.
• Persistent postural hypotension: Stop treatment.
• Restlessness, weakness, drowsiness, dizziness, dry mouth, nausea, diarrhea, abdominal pain, constipation): The dose should be reduced OR the patient should be given a suitable concomitant medication.

Therapy should be withdrawn gradually to reduce the risk of withdrawal symptoms.

Barbiturates should be given at a reduced dose.

Older patients: Use with great caution, especially in patients receiving multiple drug therapies.

Overstimulation/excessive therapeutic action: The dose should be reduced OR a phenothiazine tranquilizer should be administered concomitantly.

Adverse reactions occurring during treatment (e.g., restlessness, insomnia, weakness, drowsiness, dizziness, dry mouth, nausea, diarrhea, abdominal pain, constipation): The dose should be reduced OR the patient should be given a suitable concomitant medication.

Switching TO:

• Spinal anesthesia: Allow at least 10 days after stopping this drug.
• Other MAOIs, other antidepressants (e.g., dibenzazepines/tricyclics, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]), bupropion, or buspirone: Allow at least 14 days after stopping this drug.
• High tyramine content foods: Allow at least 14 days after stopping this drug.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or to any of the ingredients
• Patients with a history of liver disease
• Patients with abnormal liver function tests
• Patients with congestive heart failure
• Presence of pheochromocytoma
• Patients with severe renal dysfunction or renal disease

• Concomitant use with:
• Bupropion
• Buspirone
• Dextromethorphan
• Dibenzazepine-related drugs, tricyclic, and tetracyclic antidepressants (e.g., amitriptyline, amitriptyline/perphenazine, amoxapine, carbamazepine, clomipramine, cyclobenzaprine, desipramine, dosulepin, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine)
• Foods with high tyramine content (e.g., all mature/aged cheese [EXCEPT fresh cottage cheese, cream cheese, ricotta, processed cheese], all aged/cured/fermented meat/fish/poultry (e.g., pickled herring, Genoa salami, Lebanon bologna, hard salami, pepperoni), all fermented soybean products (e.g., soy sauce, miso, fermented tofu), sauerkraut, fava/broad bean pods, concentrated yeast extract (e.g., brewer's yeast), liver, all tap/draught beers, including some bottled and non-alcoholic beers
• MAOIs (e.g., furazolidone, iproniazid, isocarboxazid, moclobemide, nialamide, pargyline, pargyline/methyclothiazide, procarbazine, tranylcypromine)
• Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., fluoxetine, sertraline, paroxetine, venlafaxine)
• Some central nervous system (CNS) depressants (e.g., alcohol, narcotics, meperidine, opioids, pethidine)
• Sympathomimetic drugs (e.g., amphetamines, cocaine, dopamine, epinephrine, guanethidine, levodopa, L-tryptophan, L-tyrosine, methyldopa, methylphenidate, norepinephrine, phenylalanine, tryptophan, tyramine)
• Anesthetics
• Meperidine

US BOXED WARNINGS:
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 of major depressive disorder (MDD) and other psychiatric disorders.
• Anyone considering the use of this drug 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.
• This drug is not approved for use in pediatric patients.

Safety and efficacy have not been established in pediatric patients; this drug is not recommended for use in these patients.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken without regard to meals; however, food consumed concomitantly during administration may decrease gastrointestinal side effects.

Storage requirements:

• The manufacturer product information should be consulted.

General:

• LIMITATION OF USE: This drug is not indicated for use during the manic phase.

Monitoring:

• Cardiovascular: Blood pressure, heart rate, signs/symptoms of hypertensive crisis and palpitations
• Hepatic: Liver function tests
• Nervous system: Headaches (change or presence)
• Psychiatric: Emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Patient advice:

• Patients should be told not to take sympathomimetic drugs (including amphetamines, cocaine, methylphenidate, dopamine, epinephrine, and norepinephrine) or related compounds (including methyldopa, L-dopa, L-tryptophan, L-tyrosine, and phenylalanine).
• Patients should avoid high protein foods that have undergone protein breakdown by aging, fermentation, pickling, smoking, or bacterial contamination.
• Patients should avoid cooked or plain cheeses (especially aged varieties), pickled herring, beer, lager, wine, alcohol-free or reduced-alcohol beer or wine, liver, yeast extract (including large quantities of brewer's yeast and Marmite), dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna), pods of broad beans (fava beans), sauerkraut, meat extract, flavored textured vegetable protein, fermented soya bean extract, hung game, and yogurt.
• Tyramine levels in foods vary brand to brand and batch to batch; having no reaction to a prohibited food on one occasion does not mean they will not react on a different occasion.
• Excessive amounts of caffeine and chocolate may cause hypertensive reactions; patients should be told to avoid excessive amounts of chocolate or caffeine (e.g. tea and coffee).
• Patients should avoid the following over-the-counter medications: cold and cough preparations (including those with dextromethorphan), nasal decongestants (tablets, drops, or spray), hay fever medications, sinus medications, anti-appetite medicines, weight reducing preparations, "pep" pills, L-tryptophan containing preparations.
• Patients should be instructed to inform their other healthcare providers (including their dentist) that they are using this drug.
• Patients should promptly report headache, palpitations, throat tightness, or other unusual symptoms (e.g., neck stiffness, nausea, vomiting, chest constriction, tachycardia, sweating, dizziness).
• This medicine may cause impaired judgment, thinking, or motor skills; patients should be instructed to avoid driving a car or operating dangerous machinery until they know how this drug affects them.

Frequently asked questions

• What are some common side effects of antidepressants?