Moclobemide (Manerix)

Primer

Moclobemide (Tradename: Manerix) is a reversible inhibitor of monoamine oxidase A (RIMA) used in the treatment of major depressive disorder and social anxiety.

Pharmacokinetics

See also article: Introduction to Pharmacology

Pharmacokinetics of Moclobemide

Absorption	Rapidly absorbed from gut; absorption increases from 50% with 1st dose, to 90% after 2 weeks.
Distribution	Relatively lipophillic; 50% bound to albumin
Metabolism	Liver; CYP enzymes
Elimination	Urine
Half-life	1-4 hours

Cytochrome P450 Metabolism

See also article: Cytochrome (CYP) P450 Metabolism

Moclobemide: Cytochrome P450 Metabolism

Substrate of (Metabolized by)	CYP 2C19, 2D6
Induces	-
Inhibits	-

Pharmacodynamics

Mechanism of Action

Moclobemide selectively and reversibly inhibits monoamine oxidase A (MAO-A). This inhibition decreases the metabolism and destruction of monoamines in synapses. This results in an increase in the monoamines including serotonin, norepinephrine, and dopamine.

Toxicity

In overdose, moclobemide alone is relatively safe. However, a combination overdose with moclobemide plus an SSRI/SNRI may be lethal.

Indications

Dosing

Dosing for Moclobemide

Starting	300mg in divided doses (i.e. - 150mg po BID), some may respond only on 150mg a day; the usual dose range is 300-600mg.
Titration	Increase by 150mg every 1 week
Maximum	600mg daily
Taper	Taper over the course of at least several weeks. When stopping moclobemide and switching to a new antidepressant, wait at least 24 hours for moclobemide to wash out (See also: Tapering/Switching Antidepressants)

Formulations

Moclobemide comes in a tablet form, in 100 mg 150 mg and 300 mg doses.

Monitoring

There is generally no dietary monitoring needed, if individuals are on doses >600 mg a day, then they should minimize the consumption of tyramine-rich foods.
- Thus, individuals should avoid eating too much Marmite or strong or aged cheeses.
Once daily dosing may be as effective as twice daily dosing, but twice daily is recommended due to the short half-life.

Dietary Restriction

Even though moclobemide is an MAOI, it does not mean the patient needs to have special dietary restrictions. Clinical studies have shown that up to 100 mg tyramine can be safely ingested during treatment on moclobemide doses of up to 600 mg per daily (when given after meals). 100 mg of tyramine is the equivalent of 1,000 g to 2,000 grams of mild cheese, or 200 grams strong cheese, or 70 grams Marmite yeast extract!^[1]

Contraindications

Absolute

In patients with a known hypersensitivity to moclobemide.
In patients with delirium
Concomitantly with tricyclic/tetracyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotoninnorepinephrine reuptake inhibitors (SNRIs) or conventional monoamine oxidase inhibitors (MAOIs), due to risk for serotonin syndrome.
Selegiline, meperidine (death has occurred in patients receiving a conventional MAO inhibitor and meperidine (pethidine) given concomitantly), thioridazine, dextromethorphan (contained in many proprietary cough medicines) bupropion, triptans, and tramadol.

Relative

Dose should be cut in half in individuals with severe liver impairment.

Drug-Drug Interactions

Switching From One Antidepressant to Another

When someone is already on an antidepressant such as an SSRI, and you want to stop it and switch over to moclobemide, you should have a 2-week washout period before starting moclobemide!

Side Effects

Common side effects include insomnia, sedation, increased anxiety, tachycardia, nausea, diarrhea, or headaches.
Anticholinergic effects include dry mouth or blurred vision.
There is a low incidence of sexual dysfunction (24% vs. 62% for SSRIs).^[2]

Adverse Events

Serotonin syndrome
Hypertensive reactions can occur in individuals with thyrotoxicosis or pheochromocytoma.

Clinical Pearls

May be the best tolerated antidepressant as there are no sexual side effects and no dietary restrictions as might be required in other MAOIs.
Moclobemide increases REM sleep latency and slightly decreases REM sleep %.^[3]
Should be taken after meals to avoid tyramine-related effects such as headaches.

Special Populations

Geriatric

See main article: Geriatric Pharmacology

Pediatric

See main article: Pediatric Pharmacology

Obstetric and Fetal

See main article: Obstetric and Fetal Pharmacology

Medically Ill

See main article: Psychotropic Dosing in the Medically Ill

Resources

¹⁾ Health Canada. PRODUCT MONOGRAPH PrMANERIX® (moclobemide) 150 mg & 300 mg Film-Coated Tablets

²⁾ Kennedy, S. H., Ralevski, E., Davis, C., & Neitzert, C. (1996). The effects of moclobemide on sexual desire and function in healthy volunteers. European neuropsychopharmacology, 6(3), 177-181.

³⁾ Monti, J. M., Alterwain, P., & Monti, D. (1990). The effects of moclobemide on nocturnal sleep of depressed patients. Journal of Affective Disorders, 20(3), 201-208.

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