MAOIs – Choices

There are many differences in side effects between phenelzine (a hydrazine derivative) and tranylcypromine (non-hydrazine).

Hydrazines (phenelzine) inactivate vitamin B6 causing deficiency and are also liver toxic (tranylcypromine is not), which is why most of them were withdrawn from the market.

Phenelzine (unlike tranylcypromine) may be metabolised by acetylation which shows great genetic variation. The possible implication of this is the dose may have to be greatly varied between patients depending on their genetic acetylater status. A further difference and potential complication is that phenelzine has non-linear pharmacokinetics because it both blocks, and is metabolised by, monoamine oxidase.

Phenelzine also potentiates hypoglycaemia due to a direct influence on gluconeogenesis (related to its hydrazine structure). Tranylcypromine does not appear to have an adverse effect on diabetes and does not affect gluconeogenesis.

Phenelzine raises brain GABA levels.

Also, side effects:–

  • phenelzine:- marked weight gain, oedema and sedation are common,
  • tranylcypromine:- minimal or no weight gain, sedation and oedema much less frequent.

The evidence concerning overall side effects indicates that tranylcypromine has sufficient advantages over phenelzine to conclude that it is probably best to save phenelzine for your second choice.

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Dr Ken Gillman