Pregnancy

• 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 are 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

MOCLOBEMIDE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Atypical depression

• Severe depression

• Treatment-resistant depression or anxiety disorders

Potential Disadvantages

• Patients noncompliant with dietary restrictions, concomitant drug restrictions, and twice daily dosing after meals

Primary Target Symptoms

• Depressed mood

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 his/her doctor because of possible drug interactions with the MAOI

• Headache is often the first symptom of hypertensive crisis

• Moclobemide has a much reduced risk of interactions with tyramine than nonselective MAOIs

• Especially at higher doses of moclobemide, foods with high tyramine need to be avoided (see Table 3)

• The rigid dietary restrictions may reduce compliance

✽ May be a safer alternative to classical irreversible nonselective MAO-A and MAO-B inhibitors with less propensity for tyramine and drug interactions and hepatotoxicity (although not entirely free of interactions)

• May not be as effective at low doses, and may have more side effects at higher doses

• Moclobemide’s profile at higher doses may be more similar to classical MAOIs

• 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

Amrein R, Martin JR, Cameron AM. Moclobemide in patients with dementia and depression. Adv Neurol 1999;80:509–19.

Fulton B, Benfield P. Moclobemide. An update of its pharmacological properties and therapeutic use. Drugs 1996;52:450–74.

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.

Nutt D, Montgomery SA. Moclobemide in the treatment of social phobia. Int Clin Psychopharmacol 1996;11(Suppl 3):S77–82.

MODAFINIL

MODAFINIL: THERAPEUTICS

Brands

• Provigil

• Alertec

• Modiodal

see index for additional brand names

Generic?

Yes

Class

• Wake-promoting

Commonly Prescribed for

(bold for FDA approved)

• Reducing excessive sleepiness in patients with narcolepsy and shift work sleep disorder

• Reducing excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) (adjunct to standard treatment for underlying airway obstruction)

• Attention deficit hyperactivity disorder (ADHD)

• Fatigue and sleepiness in depression

• Fatigue in multiple sclerosis

• Bipolar depression