Monoamine Oxidase Inhibitors - MAOIs
Examples
Non selective - these drugs have been superseded by newer anti-depressants, but are still used occasionally
MAOA
MAOB
Indications
Treatment of refractory depression Parkinson's Disease (selegiline).
Contraindications
Contraindications
- Cerebrovascular disease
- Phaeochromocytoma
- Mania
Caution
- Diabetes mellitus
- Cardiac disease, hypertension, arrhythmias
- History of psychotic illness
- Hepatic insufficiency
- Elderly
- Concurrent electric convulsive treatment
Mechanism
Amine neurotransmitters (e.g. 5HT, catecholamines, dopamine) are broken down to inactive metabolites by the enzyme monoamine oxidase (MAO), of which two isoforms exist, in nerve terminals. MAOA is found principally in the gut and liver and MAOB is found in the brain. Monoamine oxidase inhibitors act to prevent the breakdown of amine neurotransmitters by irreversibly binding with the enzyme ( except moclobemide which binds reversibly).
Administration
All drugs are taken orally.
Specialist initiation only.
Adverse Reactions
- Tyramine (cheese) reaction - Tyramine in foodstuffs is not broken down by bound MAOA and enters circulation causing dangerous hypertension due to its sympathomimetic effect. This reaction is not caused by selegiline, and uncommon with moclobemide.
- Gastrointestinal effects
- CNS effects - dizziness, insomnia, agitation, anxiety
- Autonomic effects - dry mouth, blurred vision, postural hypotension
- Hyponatremia (leading to confusion and seizures)
Interactions
- Drugs that potentiate serotonin neurotransmission - e.g. any other antidepressant
- Oral hypoglycaemic drugs - excess hypoglycaemia
- Drugs that can precipitate tyramine reaction - other amine drugs (e.g. ephedrine and pseudoephedrine - often found in cold remedies), dopamine receptor agonists (e.g. Levodopa, cabergoline), direct sympathomimetics (e.g. lidocaine with adrenaline), opioids and associated analgesics
- Foods that can precipitate tyramine reaction - cheese, meat, yeast extract, some red wines / alcoholic drinks, e.t.c.
Patients should have a wash-out period of several weeks between stopping any antidepressants and starting MAOIs and vice versa.
Education
Patients should be warned that anti-depressants take 7-10 days to begin to work, and a month before their full benefit is seen. If effective, they should be continued for 3-12 months to avoid recurrence of symptoms upon discontinuation.
Warn patients these drugs can interfere with skilled motor tasks (e.g. driving).
Give patients taking MAOIs a warning card containing advice on how to avoid the tyramine interaction (they should avoid particular foods). They should also be warned of the signs of this reaction.
Pharmacokinetics
Monoamine oxidase inhibitors cause a rapid and sustained increase in the 5-HT, noradrenaline and dopamine content of the brain, 5-HT being affected most and dopamine least. Similar changes occur in peripheral tissues such as heart, liver and intestine, and increases in the plasma concentrations of these amines are also detectable.
