Monoamine-oxidase inhibitors

MAOIs inhibit monoamine oxidase, which is responsible for the metabolism of several neurotransmitters including serotonin, noradrenaline and dopamine.
There are two forms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, adrenaline and noradrenaline. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.
They have multiple actions. Their main uses are in the treatment of depression and Parkinson's Disease, although there has also been some research into their use in attention deficit hyperactivity disorder (ADHD).¹

The MAOIS are used much less frequently than tricyclic and related antidepressants, or than selective serotonin re-uptake inhibitors (SSRIs) and related antidepressants. However they remain a reasonable second line treatment, and should be tried in any patient refractory to treatment with other antidepressants.
They should only be prescribed either by a specialist in mental health, or a GP with a special interest in mental health.²

• MAOIs may be more effective than other treatments for atypical major depressive disorder than tricyclic antidepressants.³
• They are also said to be effective in depression where hypochondriasis, phobia or hysteria are prominent features.
• However the bulk of current research has been conducted on older, irreversible MAOIs, and further work is needed on the newer, reversible MAOIs with their improved safety profile.
• The most commonly used drug in this class is Moclobemide. It is generally well tolerated with few anti-muscarinic side-effects e.g. dry mouth, blurred vision etc.
• The irreversible MAOIs most commonly used include phenelzine and isocarboxazid. They are less stimulant, and so are safer.

Cautions

Interactions

When taken orally, MAOIs inhibit the breakdown of dietary amines. Sufficient intestinal MAO-A inhibition can lead to hypertensive crisis, when foods containing tyramine are consumed, or hyperserotonemia if foods containing tryptophan are consumed. The amount required to cause a reaction varies widely between individuals, and depends on dosage and selectivity.
The precise mechanism causing the hypertensive reaction is not known. It may be that tyramine displaces norepinephrine from storage vesicles triggering a cascade. This releases excessive amounts of norepinephrine leading to a hypertensive crisis. Hypertensive crises can sometimes result in stroke or cardiac arrhythmia if not treated. An early warning sign may be a throbbing headache.

• Indirect acting sympathomimetics, such as ephedrine or pseudoephedrine are commonly found in over-the-counter cough and cold preparations. They have a similar pressor action to the amine neurotransmitters, which can be potentiated by the presence of MAOIs.
• Tyramine rich foods such as mature cheese, pickled herring, broad bean pods and yeasty foods e.g.Bovril, Marmite and OXO
• Food that is 'going off' especially if meat, fish, poultry or offal
• Offal should be avoided
• Alcohol, or low-alcohol drinks
• Opiate analgesia, particularly pethidine. Toxicity resulting from excessive intra-synaptic serotonin, previously known as serotonin syndrome, is characterised by clonus, hyperreflexia, hyperthermia and agitation⁵. It is not known to occur with morphine, codeine, oxycodone or buprenorphine.
• 5 Hydroxytriptamine antagonists- triptans. There is a theoretical risk of increased central nervous system toxicity. The manufacturers advise avoiding triptans for 2 weeks after stopping moclobemide⁶.

The risk of all interactions persists for 2 weeks after the MAOI is stopped.

Selegiline is a monoamine-oxidase-B inhibitor. It has been shown to have a modest benefit as an initial monotherapy in Parkinson's disease. It improves the symptoms and delays the need for levodopa, when compared with placebo⁶.
It is licensed for monotherapy, or in conjunction with levodopa.
There are controversial claims that it is also neuroprotective⁷. Selegiline is generally well tolerated.
Unlike the non-selective monoamine-oxidase A or B inhibitors it DOES NOT interact with tyramine containing foods.

Adverse effects

• These include dry mouth, hypotension and insomnia. The insomnia is lessened by taking the dose in the morning.
• It is important that the dose is started low ⁸ ( e.g.2.5 mg daily) to avoid confusion and agitation, which can happen particularly in the elderly. Selegiline may potentiate levodopa adverse effects, but these can be managed by lowering the levodopa dose.