Monoamine oxidase inhibitors (MAOIs) for depression

Monoamine oxidase inhibitors (MAOIs) were the first antidepressants to be developed. They are sometimes referred to as irreversible monoamine oxidase inhibitors, and can be used to treat depression in adults.

These days, MAOIs are not often prescribed as the first treatment for depression. That’s because of their potential for serious side effects and interactions with certain foods and other medicines. However, they can be useful in treating depression when newer, safer antidepressants have not been effective.

MAOIs can also be used to treat some anxiety disorders, but again, they are not usually the first choice medicine because of the associated risks of the side effects and interactions.

MAOIs available in Australia

There are 2 types of MAOI available in Australia:

  • phenelzine (brand name Nardil); and
  • tranylcypromine (brand name Parnate).

Both are available as tablets.

How do MAOIs work?

Depression is associated with reduced levels of chemicals in the brain that transmit signals between nerve cells. These chemicals are called neurotransmitters. MAOIs increase the levels of these neurotransmitters in the brain by blocking their breakdown.

MAOIs work by blocking the monoamine oxidase enzyme, which is involved in the breakdown and removal of several of the neurotransmitters - namely, dopamine, noradrenaline and serotonin.

Diet and MAOIs

MAOIs also block the breakdown of a substance called tyramine. Tyramine is found naturally in the body as well as in certain foods and drinks, and is involved in regulating blood pressure.

Eating high-tyramine foods while taking a monoamine oxidase inhibitor can cause tyramine levels in the body to rise to dangerous levels. This can cause sudden and severe elevations in blood pressure.

People taking MAOIs need to follow a strict diet, which involves avoiding foods and drinks containing a large amount of tyramine.

What foods should be avoided when taking MAOIs?

Some of the foods and drinks that are high in tyramine and should be avoided while taking MAOIs (and for 2 weeks after stopping taking them) include:

  • matured (aged) or strong cheeses or out-of-date cheeses;
  • certain meats (e.g. salami, pepperoni, mortadella);
  • pickled herring;
  • pâté and liver;
  • Vegemite and other concentrated yeast extracts (Promite, Marmite, Bovril);
  • protein extracts;
  • soy sauce and other soybean products, such as miso and tofu;
  • banana skins, banana chips and banana-flavoured desserts (banana peel is used in flavouring);
  • fava or broad bean pods;
  • sauerkraut;
  • fermented soya beans; and
  • beer and wine.

In addition, foods such as meat, fish, poultry and eggs can contain high amounts of tyramine if they have not been stored correctly and have gone off. Excessive amounts of chocolate and caffeine should also be avoided.

If you consume any of these foods while taking a MAOI, your blood pressure may rise rapidly and you may get severe symptoms such as a throbbing headache, nausea, vomiting, or a fast heartbeat. Such a situation is a medical emergency and can be very dangerous if not treated properly. If you have a reaction after eating any of these foods, contact your doctor, call 000 for an ambulance or go to hospital immediately.

Your doctor should give you a list of all the foods and drinks you need to avoid while taking this medication. Even if you stop taking MAOIs, you’ll need to keep avoiding these foods and drinks for at least 14 days afterwards. You should also have a plan in case you accidently eat or drink something with a high level of tyramine.

MAOIs and other medicines

MAOIs interact with a long list of other medicines, so you must always check with your doctor or pharmacist before taking any other medicines, including non-prescription and complementary medicines.

It is especially important not to take certain other antidepressants when you are taking (or have recently been taking MAOIs), including SSRIs, SNRIs and tricyclic antidepressants. Painkillers such as pethidine and tramadol are other medicines that cannot be taken while you are on MAOIs. Taking these types of medicines together can cause a serious condition called serotonin toxicity.

You also should not take cold and flu preparations or any similar medicines while you are taking MAOIs, as you can develop very high blood pressure. Certain antihistamines used to treat allergies and hay fever also need to be avoided.

A variety of other medicines should also be avoided if you are taking MAOIs, including:

  • some asthma medicines;
  • blood pressure medicines;
  • weight loss medicines; and
  • some anaesthetic medicines, including certain local anaesthetics.

MAOIs also interact with illicit drugs such as amphetamines.

Your doctor or pharmacist should give you a list of all foods, drinks and medicines to avoid, and you should follow this list to the letter. Even after you stop taking MAOIs, you need to continue to avoid these foods and medicines for at least 14 days, as there is still a possibility of interactions during this period.

Taking MAOIs

When you begin treatment, your doctor will recommend starting with a low dose. The dose is then gradually increased over several days.

MAOIs are taken several times per day, and the last dose should be taken no later than early afternoon to reduce the risk of having trouble sleeping at night.

It’s important that you don’t stop taking these antidepressants suddenly. Stopping MAOIs can be associated with developing flu-like symptoms, and the risk of this is higher if you stop them suddenly. Your doctor can advise on the best way to stop these medicines to avoid withdrawal symptoms. Talk to your doctor, and if your medicine needs to be stopped, they the dose should generally be reduced slowly.

Side effects of MAOIs

MAOIs are often not the first choice of antidepressant because they are associated with many side effects. Some of these side effects include:

  • nausea;
  • low blood pressure when standing up;
  • dry mouth;
  • constipation;
  • insomnia (trouble sleeping);
  • blurred vision;
  • sexual problems;
  • rapid heartbeat; and
  • weight gain.

Who should not take MAOIs?

MAOIs should not be used by children and teenagers.

If you are pregnant or planning a pregnancy, let your doctor know, as it will impact on the type of medicine that your doctor prescribes. Your doctor will weigh up the risks and benefits of treatment for both you and your baby.

Breast feeding is not recommended if you are taking monoamine oxidase inhibitors.

Reversible inhibitors of monoamine oxidase (RIMAs)

There is another class of medicine that is similar to MAOIs – reversible inhibitors of monoamine oxidase type A (RIMAs). Moclobemide is the only medicine in this class available in Australia. Examples of brand names include Aurorix, Amira and Clobemix.

Moclobemide can be used to treat depression in adults. It can be especially helpful in people with symptoms of sleeping difficulties, anxiety and inability to concentrate. Moclobemide is generally well tolerated and is not subject to as many of the dietary restrictions as the MAOIs when taken in recommended doses.

How moclobemide works

Like the MAOIs, moclobemide works on brain chemicals, but it is more targeted. It inhibits just one of the 2 monoamine oxidase enzymes, blocking MAO type A but not type B.

This means that people taking moclobemide can generally still eat foods containing tyramine, because tyramine still gets broken down by MAO-B and doesn’t build up dangerously in the brain to cause high blood pressure. To be doubly sure, moclobemide is usually taken after food.

People taking moclobemide should still avoid cough and cold preparations that contain pseudoephedrine, and it is still prudent to check with your doctor or pharmacist before starting new prescription or over-the-counter medicines.

Taking moclobemide

Moclobemide should be taken after meals twice a day.

Side effects of moclobemide

Most people experience few side effects with moclobemide. Side effects that are associated with moclobemide, including difficulty sleeping, dizziness, nausea and headache, usually go away after a while.

Moclobemide and other medicines

Moclobemide can interact with some other medicines, but not as many as MAOIs. Medicines that should be avoided while taking moclobemide include:

  • St John’s wort;
  • Triptans (medicines used in treating migraine);
  • certain other antidepressants (including SSRIs, SNRIs and tricyclic antidepressants);
  • some painkillers; and
  • certain cough and cold medicines.

Switching antidepressant medicines

If you are changing antidepressants, your doctor will usually recommend slowly stopping the first medicine and then having a break before starting the new one. This is called a 'washout period', and it’s important because it prevents the antidepressants interacting, which can cause serious harm.

Depending on the antidepressants you are stopping and starting, the washout period may need to last for days or several weeks. The main concern is serotonin toxicity (also known as serotonin syndrome), which is an overload of serotonin in the brain.

Young people starting antidepressants

People younger than 25 years of age with depression may have a slightly increased risk of suicidal thoughts and behaviour when they first start taking antidepressants. So, close monitoring is needed in any young person taking antidepressants, especially when they are first started. Get help straight away if you experience any suicidal thoughts.

References

1. Depression in adults (Published June 2013. Amended February 2015). In: eTG complete. Melbourne: Therapeutic Guidelines Limited; 2018 Jul. https://tgldcdp.tg.org.au/ (accessed Aug 2018).
2. Mayo Clinic. Monoamine oxidase inhibitors (MAOIs) (updated 8 Jun 2016). https://www.mayoclinic.org/diseases-conditions/depression/in-depth/maois/art-20043992 (accessed Aug 2018).
3. Lampe L. Drug treatment for anxiety. Australian Prescriber 2013;36:186-9 (2 Dec 2013). https://www.nps.org.au/australian-prescriber/articles/drug-treatment-for-anxiety (accessed Aug 2018).
4. Mayo Clinic. MAOIs and diet: Is it necessary to restrict tyramine? (updated 19 Jan 2016). https://www.mayoclinic.org/diseases-conditions/depression/expert-answers/maois/faq-20058035 (accessed Aug 2018).
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