PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. MAOIs - Information, full.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

MAOIs - Information, full

MAOIs - Information, full

Date Created: 27/11/1999   Last Modified: 04/01/2003   Last Checked: 28/07/2004

Advice and information concerning 'Aurorix' 'Manerix' 'Parnate' 'Nardil' (MAOIs).

Note: insert brand/drug names as appropriate for your area for tranylcypromine, phenelzine, moclobemide.

This advice is relevant for all persons taking 'Parnate' or 'Nardil' and also for those on 'Aurorix' 'Manerix' (if taking doses above that which is deemed the 'maximum recommended' dose, which is usually said to be 600 mg daily). These drugs all belong to a group that are similar and are called Mono-Amine Oxidase Inhibitors ('MAOIs'). Moclobemide is an MAOI of the sub-type usually referred to as a 'RIMA' (Reversible Inhibitor of Monoamine oxidase-A). The enzyme 'MAO' has two sub-types, A and B, moclobemide inhibits A much more than B in normal doses, but this difference is less at higher doses.

This document covers diet (both food and drink) and also drug interactions for those on these 'MAOIs'. It is intended to inform and assist both doctors and those taking MAOIs. Note that the term 'MAOIs' does include the new sub-type of MAOIs usually referred to by the abbreviation 'RIMAs', the most widely available 'RIMA' is moclobemide.

Persons on these drugs may be advised to keep some means of identifying the fact that they are on MAOIs readily available. Similar steps as may be taken with insulin dependent diabetes and those suffering epilepsy are appropriate; this is in case of accidents or emergencies. This may be kept on the person (handbag or wallet), and also in the car (glove box) as well as at home.

Information such as that contained in here should be given to any person supplying treatment, or advising on any aspect of treatment, including 'herbalists', 'naturopaths' and any other similar therapists, as well as any dentist or any medical practitioner who is consulted.

Sticking to a simple diet is important, and necessary, whilst taking MAOIs. This is because a few foods contain a natural substance in them (called tyramine) that can make the blood pressure (BP) go dangerously high. Remember, the seriousness of any BP reaction is in proportion to the amount of any of the ‘wrong’ food (or drink) that is consumed.

The only foods that have enough tyramine in them to cause serious problems, when eaten in moderation, are those that have been subjected to the action of micro-organisms. If that has happened then such foods may sometimes contain so much tyramine that they are dangerous.

The reaction can only occur if a relatively large amount of ‘tyramine’ is eaten or drunk (see list below). It consists of a big increase in blood pressure (BP). The increase in BP is greater with larger quantities of the food; this is important to remember because there is no cause for worry if, as an example, a little grated cheese on a salad has been eaten (see the list below). The reaction could make the BP high enough to produce a severe pounding headache. This headache is unlike a usual headache because it comes on quickly and is very severe (ie painful). It usually starts soon after eating, maybe within 15 minutes, usually within one hour. Any headache starting more than two hours after eating is unlikely to be due to a high blood pressure reaction.

If such a reaction occurs, and nothing is done about it, ie getting medical help quickly, then there is a small chance that a ‘stroke’ would occur (as a result of the high BP).

Foods to be restricted or avoided because of a 'tyramine' reaction (high BP)

  1. Cheeses. Some have very high levels of tyramine, especially ‘mature’ cheese types like Stilton, Brie and Camembert, Mozzarella; the 'smellier' it is the more tyramine it contains. A twenty gram serving of a strong cheese could possibly raise the BP to a measurable extent (but not to a dangerous extent). Larger quantities become progressively more risky. Most modern supermarket processed cheese has low (to the extent of being completely safe) levels of tyramine; however tyramine levels are unpredictable, so it is risky to experiment because the worst possible outcome, even if that is remote, is a ‘stroke’. We can say that 'ricotta' and 'cottage' cheese types are always safe to eat.
  2. Extracts such as ‘Vegemite’, ‘Promite’, 'Marmite', ‘Bovril’ must be avoided. Foods like soy sauce, 'tofu' and 'miso' are made in a similar way; ie by 'fermentation' of brews containing proteins, so only small amounts can be safely eaten. Because the BP goes up in proportion to the amount of tyramine that is eaten, it is OK to have small quantities (see below for what 'small' really means).
  3. Meat products are safe, but if they are not fresh, ie if they have been subject to decomposition by micro-organisms, then they may be risky; eg liver pate (and similar meat or fish pastes) are perfectly safe if freshly made and properly refrigerated. But after a couple days left out at room temperature they could be risky. Similarly 'salami' and 'pepperoni' sausages, and dried meats, are usually OK but caution is warranted. Liver that is near its' 'use by' date when purchased, and is then kept in a domestic fridge that is not cold enough, may possibly be risky.
  4. Alcoholic drinks in true moderation (two drinks in any six hour period) is very likely to be safe. Modern hygienic production methods will make excessive tyramine levels rare. Badly made or stored drinks may be risky, so avoid ‘home made’ wines or beers. Bottled beer is almost certain to be safe; but avoid ‘live’ beers which may be available from 'boutique' producers. They can be distinguished by the sediment (of dead yeast) in the bottom and they are cloudy if shaken. Also ‘keg’ or 'tap' beers may sometimes have significant tyramine levels and are best avoided.
  5. Sauerkraut can sometimes contain sufficient tyramine levels to warrant restriction (see below) and broad (fava) beans are OK but the bean pods should not be eaten.

Other non-serious interactions that are not dangerous

Many plant derived substances, eg 'herbs' and 'foods' like chocolate, coffee, and tea contain chemical compounds that act as 'drugs', eg stimulants like caffeine. These effect everyone but may have an exaggerated effect in those taking various sorts of antidepressant drugs, including MAOIs; they should be taken in moderation and avoided if they precipitate symptoms such as anxiety, jitteriness, agitation, poor sleep etc.

MAOIs, including 'Aurorix' 'Manerix' and 'Eldepryl' / 'Selgene' - Interactions with other drugs

Different kinds of 'psychotropic' drugs (ie those that effect the brain) should not be mixed without appropriate medical advice. This, of course, includes both alcohol and 'illicit' drugs, some of which may prove fatal if mixed with MAOIs, eg 'ecstasy'. Remember the term 'psychotropic' includes, among other drugs, narcotic analgesics, anti-histamines and anti-epileptic drugs as well as 'herbal' preparations like St John's Wort and ginseng.

Note especially:-- cough and cold remedies available 'over the counter' must be checked. The anti-histamines brompheniramine or chlorpheniramine are best avoided because they are SRIs (serotonin reuptake inhibitors), other anti-histamines are safe.

Analgesics (pain killers) that are safe to take with MAOIs:-- Aspirin and Paracetamol and all the 'NSAIDs' (anti-inflammatory drugs used for arthritis) are safe, such as:-- brufen, ibuprofen, mefenamic acid, naproxen, indomethacin, phenylbutazone.

All anti-anxiety drugs (benzodiazepines) like diazepam, oxazepam and temazepam are quite safe.

Stronger analgesics that are safe are:-- codeine, oxycodone, fentanyl, buprenorphine and morphine. Some other strong analgesics are dangerous (see below).

Dangerous analgesics

The risk with analgesics (and 'SSRI' type antidepressant drugs) is that of 'serotonin syndrome', not a hypertensive episode as with tyramine. These two reactions are quite different (see 'Psychopharmacology update notes'; and also do please note that many supposedly authoritative current texts contain serious inaccuracies). The analgesics that are dangerous are dangerous because they possess the property of acting as serotonin reuptake inhibitors. That is they act like the serotonin reuptake inhibitor (SSRI) antidepressants. Pethidine and tramadol are 'SRIs' and must not be given to anyone on MAOIs (especially dangerous if given via the intravenous or intramuscular route). Dextromethorphan, (dextro)propoxyphene and pentazocine should also be avoided.


Antidepressant drugs

Any antidepressant drug that works as a serotonin reuptake inhibitor is potentially dangerous (possibly even fatal) if combined with any MAOI, even the newer 'RIMAs' that are said to be 'selective' and 'reversible'. If people have been taking any serotonin reuptake inhibitor type drug including:-- sertraline, paroxetine, fluvoxamine, cipramil, clomipramine, or imipramine, milnacipran, venlafaxine, duloxetine or sibutramine within two or three weeks specialist advice may be needed before starting MAOIs (including 'Aurorix', and 'Eldepryl' and 'Selgene'). Washout intervals varying between one and five weeks may be required for these drugs.

If fluoxetine has been taken (Prozac and other names) at any time within the previous three months caution is required and specialist advice may be needed before starting various other drugs, but particularly MAOIs (including 'Aurorix'/'Manerix' and 'Eldepryl' / 'Selgene'); this is because fluoxetine has a very long elimination half-life in some people (it takes a long time to get out of the system).


Ceasing treatment

This advice should be followed for a minimum of two weeks (six weeks in some situations) after ceasing these drugs (between one and three days in the case of moclobemide).

Medical treatment of high BP

If the blood pressure is very high then drugs may be given to reduce it; eg oral nifedipine 10 mg, phentolamine 5-10 mg IV, or chlorpromazine 25-50 mg IMI or IV.


How much is safe?

Many people on MAOIs can ingest up to about 25 mg of tyramine (as part of a meal) without experiencing a medically dangerous level of hypertension. However, there is a lot of individual variation in sensitivity to tyramine. It seems reasonable to aim not to exceed an intake of 25 mg of tyramine. However some people may get significant reactions with as little as 5-10 mg of tyramine. A quantity of 50 grams of high tyramine content cheese could contain as much as 25 mg of tyramine and would therefor be likely to be safe for many people on an MAOI. Similarly 25 ml of soy sauce might contain as much as 25 mg of tyramine.

Tyramine in liquids taken on an empty stomach should be regarded as a separate issue. This is because they are likely to be absorbed much more rapidly. One small (330 ml) glass of some ('keg or tap') beers could have up to 30 mg of tyramine; this might be sufficient to cause a serious reaction in some people if taken on an empty stomach.

The variability between people will mean that it is possible that a undetermined percentage of people may experience a severe reaction with less than 25 mg of tyramine.

The following list gives an indication of likely tyramine levels for relevant substances

  • A selection of 43 soft and hard cheeses:-- up to 60 mg per 100 grams (600 mg per kilo)
  • Soy sauce:-- Maximum:-- 940 mg per litre (approx 1 mg per ml). Most samples measured have ranged between 10-200 mg per litre
  • Soy bean products,
  • 'tofu':-- fresh, less than 1 mg per 100 grams
  • 'tofu':-- 7 days refrigerated, 16 mg per 100 grams
  • 'Soya bean curd':-- fresh, less than 1 mg per 100 grams
  • 'Soya bean curd':-- 7 days refrigerated, less than 1 mg per 100 grams
  • 'miso' soup etc. max ~ 100 mg per 100 ml

  • 'Keg' or 'tap' beers:-- 25 to 100 mg per litre
  • Bottled beers:-- 10 mg per litre
  • Air-dried sausage:-- 25 mg per 100 grams
  • Fish products:-- up to 16 mg per 100 grams
  • Ripe banana peel:-- 6.5 mg per 100 grams
  • Protein extracts:-- three brands of meat extract contained 10, 20 and 30 mg per 100 grams
  • Sauerkraut:-- varies from 2 to 10 mg per 100 grams
  • Raw fish up to 2.6 mg per 100 grams

100 grams of cheese is a piece approx 6 x 6 x 3 cms (look at a standard 100 g pack of butter next time you have the chance to get a clear mental picture of how big a piece that is).

50 mg of tyramine per 100 grams of the strongest cheese is the max likely concentration

25 mg of ingested tyramine as the minimum than is capable of inducing a dangerous blood pressure increase.

It follows that the approx worst case scenario is that 50 grams of a very strong cheese could possibily produce a potentially dangerous reaction: ie a piece 6 x 3 x 3 cms in size.