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Antidepressants - Combinations with MAOIs

Date Created: 04/04/1999 Last Modified: 07/10/2002 Last Checked: 05/04/2003

Combinations of MAOIs and TCAs got a bad name in the sixties because imipramine was used. It occasionally proved to have enough activity as an serotonin reuptake inhibitor to cause serotonin toxicity (serotonin syndrome). Such reactions were not then understood. Serotonin toxicity reactions were sometimes wrongly interpreted as ‘hypertensive’ reactions.

Many current pharmacological texts still get all this wrong by mixing up serotonin syndrome and tyramine induced hypertension. The irony is that mixing a TCA (one which is not also an SRI-- see relevant notes on ‘serotonin syndrome’) with an MAOI makes it safer! (see references). This is because the ‘cheese’ reaction (potentially catastrophic hypertension) requires that the provoking dietary component (the amino acid tyramine) must first enter the pre-synaptic nerve, from whence it displaces noradrenalin which then mediates the hypertension.

Tyramine is actively moved into the pre-synaptic nerve by the very same ‘reuptake’ mechanism that is blocked by TCAs, which are non-specific noradrenalin reuptake inhibitors ‘NRIs’!