Moclobemide

Moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA) used for depression and social anxiety disorder. It carries a much lower risk of tyramine reactions than irreversible MAOIs and needs only modest dietary caution, but it can still cause serotonin syndrome with serotonergic drugs. It is not available in the United States.

Classification. Reversible inhibitor of MAO-A (RIMA), benzamide structure.

Mechanism. Reversibly inhibits MAO-A, raising serotonin, noradrenaline and dopamine. Tyramine can displace it from the enzyme, which explains the lower crisis risk.

Pharmacokinetics. Well absorbed; extensive first-pass metabolism reduces on repeated dosing. Metabolised by CYP2C19 and CYP2D6. Half-life 1 to 2 hours; enzyme activity returns within about 24 hours of stopping.

All regimens are oral with no loading dose.

Major depression, adults.

• Start 300 mg daily in 2 divided doses after food.
• Titration: after 1 week, increase to 450 or 600 mg daily if needed.
• Maximum 600 mg daily in 2 to 3 divided doses.
• Duration: at least 6 months after remission.

Social anxiety disorder (licensed in some regions). 300 mg daily for 3 days, then 600 mg daily in 2 divided doses. Continue for 8 to 12 weeks before judging response.

Dose limits. Severe liver impairment: reduce to one third to one half of the usual dose. Cimetidine, omeprazole, fluoxetine or fluvoxamine: reduce the dose by one half. Kidney impairment and older adults: no adjustment.

Switching. Wait at least 24 hours after stopping moclobemide before starting another antidepressant, and at least 14 days after stopping a non-MAOI antidepressant before starting moclobemide (5 weeks after fluoxetine).

Contraindications. Acute confusional states, phaeochromocytoma, use with selegiline, SSRIs, SNRIs, tricyclics, pethidine, tramadol, dextromethorphan or triptans, children, hypersensitivity.

Serious adverse effects. Boxed-warning-level risk of suicidal thinking and behaviour in under 25 years. Serotonin syndrome with serotonergic drugs, hypertensive reaction with large tyramine loads or sympathomimetics, hyponatraemia, mania, seizures, hepatic injury (rare).

Common adverse effects. Insomnia, nausea, dizziness, agitation, headache, dry mouth, sleep disturbance.

Interactions. Large amounts of tyramine-rich food (over about 100 g of mature cheese or similar, concentrated yeast extracts) can raise blood pressure. Khat and sympathomimetics (pseudoephedrine, ephedrine, amphetamines) must be avoided. Cimetidine, omeprazole and fluvoxamine raise levels. Opioids (pethidine, tramadol) and dextromethorphan risk serotonin syndrome.

Common prescribing errors. Taking doses on an empty stomach; combining with an SSRI; not warning about over-the-counter cold remedies; starting too soon after fluoxetine.

Special groups.

• Pregnancy: limited data; use only if benefit outweighs risk.
• Breastfeeding: low amounts in milk; monitor the infant.
• Children: not advised.
• Older adults: no adjustment; check sodium.
• Kidney impairment: no adjustment.
• Liver impairment: reduce the dose to one third to one half of the usual dose in severe impairment.

Formulations. Tablets 150 mg and 300 mg. Take after meals.

Baseline. Blood pressure, mood history including past mania, suicide risk, medicines list including over-the-counter drugs, dietary and khat use.

Monitoring. Review within 1 to 2 weeks and after each dose change for suicidality. Check blood pressure if headache or palpitations occur. If there is no improvement after 4 to 6 weeks at 600 mg daily, switch.

Stopping. Taper over 2 to 4 weeks; discontinuation symptoms are uncommon.

Referral and escalation. Refer to psychiatry for suicidal intent, psychosis, mania or failure of two adequate courses. Severe headache with palpitations or suspected serotonin syndrome needs emergency care.