The new antidepressants

Editor, – We enjoyed reading the informative article on'The new antidepressants' by Associate Professor J.W.G. Tiller (Aust Prescr 1995;18:92-6). We were also pleased to note that attention was drawn to the potential for interactions with drugs which interfere with the metabolic pathways of the various antidepressants. Unfortunately, some of the information with regard to hepatic metabolism was incorrect.

Moclobemide is metabolised by cytochrome P450 2C19 (CYP2C19)¹, not by cytochrome P450 2D6 (CYP2D6) as was stated. Confusion may have arisen because moclobemide does inhibit the metabolism of those drugs dependent on CYP2D6 for their elimination.² Interactions are therefore possible.

With regard to the selective serotonin reuptake inhibitors (SSRIs), the article correctly stated that they may inhibit CYP2D6 and hence elevate plasma concentrations of drugs metabolised by this pathway, such as the tricyclic antidepressants. However, Table 1, which listed drugs metabolised by CYP2D6, was incorrect in a number of ways. It omitted many drugs known to be metabolised by the pathway, but included several that are not: theophylline, warfarin, prednisone and felodopine are all metabolised by other cytochrome P450s. Once again the confusion may have been due to the fact that metabolism of these drugs may indeed be inhibited by the SSRIs which inhibit several different P450s.³

Full information on the metabolic pathways of the SSRIs themselves is not yet available. Paroxetine is predominantly, and fluoxetine partially, metabolised by CYP2D6, but the enzymes that predominantly metabolise fluoxetine and sertraline have not been established. If these are members of other P450 families, there would be potential for a range of possible interactions.

Your readers should be aware that full information about pathways of metabolism and potential for interactions is not always available when new drugs are marketed. Care should always be taken when prescribing in combination with other medications.

J. Hoskins, A. Gross and G. Shenfield
Department of Clinical Pharmacology
Royal North Shore Hospital
St Leonards, N.S.W.

Editor, – Australian Prescriber vol. 18 no. 4 has some excellent articles which I enjoyed reading and which are very useful for our undergraduate medical students.

I wish to draw to your attention the article by Professor Tiller on new antidepressants and, in particular, his Table 1 on page 93. This Table, which is headed 'Some drugs, metabolised by the cytochrome P450 2D6 hepatic microsomes, which may have clinically significant interactions with SSRI antidepressants', lists 7 drugs. It is my understanding that neither theophylline, warfarin, prednisone or felodipine are metabolised by cytochrome P450 2D6, but rather by other cytochrome P450 isoforms.

Associate Professor A. Somogyi
Department of Clinical and Experimental Pharmacology
University of Adelaide Adelaide, S.A.

Associate Professor J. Tiller, the author of the article, comments:

Drs Hoskins, Gross and Shenfield and Associate Professor Somogyi highlight the important issue that full information about pathways of metabolism and the potential for interaction is not always available when new drugs are marketed. This knowledge is gained over time. I thank them for providing data on metabolism and interactions with antidepressants which update and correct some data in my paper.