MAO B Inhibitors

Monoamine oxidase B inhibitors irreversibly or reversibly block the enzyme that breaks down dopamine in the brain, prolonging the effect of dopamine and levodopa. They are used alone in early Parkinson disease and as add-on in fluctuating disease.

Pharmacokinetics. Selegiline and rasagiline are irreversible inhibitors, so effect lasts about 2 weeks after stopping. Safinamide is reversible and also reduces glutamate release. Selegiline is metabolised to amphetamine derivatives.

• Rasagiline 1 mg once daily.
• Selegiline 5 mg with breakfast and lunch, or 10 mg once daily in the morning.
• Safinamide 50 mg once daily, increased to 100 mg after 2 weeks; add-on to levodopa only.

Differences. Rasagiline has no amphetamine metabolites, so less insomnia. Safinamide acts on off time and dyskinesia as an add-on. Selectivity for MAO-B is lost with selegiline over 10 mg daily.

• Early disease: monotherapy with mild symptomatic benefit; useful where levodopa is to be delayed.
• Wearing-off: add to levodopa to reduce off time by about 1 hour daily; reduce the levodopa dose by 10 to 30 percent if dyskinesia appears.
• Diet: tyramine restriction is not needed at these doses.

Selection. Check every other prescribed drug first; interactions are the main hazard.

Contraindications. Other MAO inhibitors, including linezolid and moclobemide. Pethidine, tramadol, methadone and dextromethorphan. Phaeochromocytoma. Safinamide in severe liver impairment.

Adverse effects. Insomnia (selegiline), headache, nausea, orthostatic hypotension, dyskinesia, hallucinations, impulse control disorders. Possible increased risk of melanoma in Parkinson disease.

Interactions. SSRIs, SNRIs and tricyclic antidepressants risk serotonin syndrome; allow 5 weeks after stopping fluoxetine and 14 days after stopping a MAO-B inhibitor before starting an SSRI. Sympathomimetics (pseudoephedrine, phenylephrine) can cause hypertensive crisis. Ciprofloxacin raises rasagiline levels; give 0.5 mg daily. Stop at least 14 days before elective surgery needing opioids.

Special groups.

• Pregnancy: avoid.
• Breastfeeding: avoid.
• Older adults: lower doses if hallucinations occur.
• Liver impairment: rasagiline 0.5 mg daily in mild impairment, avoid in moderate and severe; safinamide 50 mg maximum in moderate.
• Kidney impairment: no adjustment.

Monitoring. Blood pressure, mood, sleep, skin examination, and a drug review at each prescribing change.

Referral and escalation. Agitation, fever, tremor and diarrhoea with a serotonergic drug (serotonin syndrome) need immediate drug withdrawal and emergency care.