Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• Not generally recommended for use during pregnancy, especially during first trimester

• Should evaluate patient for treatment with an antidepressant with a better risk/benefit ratio

Breast Feeding

• Some drug is found in mother’s breast milk

• Effects on infant unknown

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Should evaluate patient for treatment with an antidepressant with a better risk/benefit ratio

TRANYLCYPROMINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Atypical depression

• Severe depression

• Treatment-resistant depression or anxiety disorders

Potential Disadvantages

• Requires compliance to dietary restrictions, concomitant drug restrictions

• Patients with cardiac problems or hypertension

• Multiple daily doses

Primary Target Symptoms

• Depressed mood

• Somatic symptoms

• Sleep and eating disturbances

• Psychomotor retardation

• Morbid preoccupation

Pearls

• MAOIs are generally reserved for second-line use after SSRIs, SNRIs, and combinations of newer antidepressants have failed

• Patient should be advised not to take any prescription or over-the-counter drugs without consulting their doctor because of possible drug interactions with the MAOI

• Headache is often the first symptom of hypertensive crisis

• The rigid dietary restrictions may reduce compliance (see Table 2 after Pearls)

• Mood disorders can be associated with eating disorders (especially in adolescent females), and tranylcypromine can be used to treat both depression and bulimia

• MAOIs are a viable second-line treatment option in depression, but are not frequently used

✽ Myths about the danger of dietary tyramine can be exaggerated, but prohibitions against concomitant drugs often not followed closely enough

• Orthostatic hypotension, insomnia, and sexual dysfunction are often the most troublesome common side effects

✽ MAOIs should be for the expert, especially if combining with agents of potential risk (e.g., stimulants, trazodone, TCAs)

✽ MAOIs should not be neglected as therapeutic agents for the treatment-resistant

• Although generally prohibited, a heroic but potentially dangerous treatment for severely treatment-resistant patients is for an expert to give a tricyclic/tetracyclic antidepressant other than clomipramine simultaneously with an MAO inhibitor for patients who fail to respond to numerous other antidepressants

• Use of MAOIs with clomipramine is always prohibited because of the risk of serotonin syndrome and death

• Amoxapine may be the preferred trycyclic/tetracyclic antidepressant to combine with an MAOI in heroic cases due to its theoretically protective 5HT2A antagonist properties

• If this option is elected, start the MAOI with the tricyclic/tetracyclic antidepressant simultaneously at low doses after appropriate drug washout, then alternately increase doses of these agents every few days to a week as tolerated

• Although very strict dietary and concomitant drug restrictions must be observed to prevent hypertensive crises and serotonin syndrome, the most common side effects of MAOI and tricyclic/tetracyclic combinations may be weight gain and orthostatic hypotension

Table 1. Drugs contraindicated due to risk of serotonin syndrome/toxicity

Do Not Use:
Antidepressants	Drugs of Abuse	Opioids	Other
SSRIs	MDMA (ecstasy)	Meperidine	Non-subcutaneous sumatriptan
SNRIs	Cocaine	Tramadol	Chlorpheniramine
Clomipramine	Methamphetamine	Methadone	Brompheniramine
St. John’s wort	High-dose or injected amphetamine	Fentanyl	Dextromethorphan
			Procarbazine?

Table 2. Dietary guidelines for patients taking MAOIs

Foods to avoid*	Foods allowed
Dried, aged, smoked, fermented, spoiled, or improperly stored meat, poultry, and fish	Fresh or processed meat, poultry, and fish; properly stored pickled or smoked fish
Broad bean pods	All other vegetables
Aged cheeses	Processed cheese slices, cottage cheese, ricotta cheese, yogurt, cream cheese
Tap and unpasteurized beer	Canned or bottled beer and alcohol
Marmite	Brewer’s and baker’s yeast
Sauerkraut, kimchee
Soy products/tofu	Peanuts
Banana peel	Bananas, avocados, raspberries
Tyramine-containing nutritional supplement

* Not necessary for 6-mg transdermal or low-dose oral selegiline

Table 3. Drugs that boost norepinephrine: should only be used with caution with MAOIs

Use With Caution:
Decongestants	Stimulants	Antidepressants with norepinephrine reuptake inhibition	Other
Phenylephrine	Amphetamines	Most tricyclics	Phentermine
Pseudoephedrine	Methylphenidate	NRIs	Local anesthetics containing vasoconstrictors
	Cocaine	NDRIs
	Methamphetamine
	Modafinil		Tapentadol
	Armodafinil

Suggested Reading

Baker GB, Coutts RT, McKenna KF, Sherry-McKenna RL. Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review. J Psychiatry Neurosci 1992;17:206–14.

Kennedy SH. Continuation and maintenance treatments in major depression: the neglected role of monoamine oxidase inhibitors. J Psychiatry Neurosci 1997;22:127–31.

Lippman SB, Nash K. Monoamine oxidase inhibitor update. Potential adverse food and drug interactions. Drug Saf 1990;5:195–204.

Thase ME, Triyedi MH, Rush AJ. MAOIs in the contemporary treatment of depression. Neuropsychopharmacology 1995;12:185–219.

TRAZODONE

TRAZODONE: THERAPEUTICS

Brands

• Desyrel

• Oleptro

see index for additional brand names

Generic?

Yes

Class

• SARI (serotonin 2 antagonist/reuptake inhibitor); antidepressant; hypnotic

Commonly Prescribed for

(bold for FDA approved)

• Depression

• Insomnia (primary and secondary)

• Anxiety

How the Drug Works

• Blocks serotonin 2A receptors potently

• Blocks serotonin reuptake pump (serotonin transporter) less potently

How Long Until It Works

✽ Onset of therapeutic actions in insomnia are immediate if dosing is correct

• Onset of therapeutic actions in depression usually not immediate, but often delayed 2–4 weeks whether given as an adjunct to another antidepressant or as a monotherapy

• If it is not working within 6–8 weeks for depression, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of symptoms in depression and to reduce symptoms of chronic insomnia