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The new antidepressants

Editor, – I refer to the articles by Professor J. Tiller (Aust Prescr1995;18:92-6) and Professor G. Shenfield (Aust Prescr 1995;18:100-1) on the new antidepressants. The new drugs are being compared with tricyclics (TCAs) in a way which one can only describe as disingenuously simplistic. The tricyclics are a heterogeneous group and vary greatly in their binding affinity at various receptors. For instance, desipramine is 1000-fold more potent, as a noradrenaline reuptake inhibitor, than trimipramine. Also plasma levels of TCAs vary greatly. Thus, comparing all 'TCAs' with SSRIs is misleading. Comparing therapeutic levels of desipramine and nortriptyline would be more appropriate.

The statement by Professor Shenfield regarding MAOIs that 'numerous serious interactions with a range of other drugs including TCAs.....' requires putting into perspective. Despite treating about 1000 patients with MAOIs in my career, I have rarely seen even minor morbidity from hypertensive reactions, which are easily treatable. I have managed many thousand 'patient years' of combinations(of MAOIs with TCAs) and never seen problems (one avoids clomipramine and imipramine which have clinically significant serotonin reuptake inhibition capacity).

In contrast, I have seen quite a few serious serotonin syndrome reactions already and a computer search shows a rapid increase in reports from 8 in1992, to 16 in 1994, and 12 in the first 7 months of 1995. There is no effective treatment for this potentially fatal interaction; bathroom cupboards every where now contain both moclobemide and SSRIs; individually very safe, when combined, potentially fatal.

P.K. Gillman
Mount Pleasant, Qld


Authors' comments

Professor G. Shenfield, the author of the article on the use of moclobemide with other antidepressants, comments:

I am grateful to Dr Gillman for his comments which support my suggestion that moclobemide may have serious interactions with the SSRIs. My statement on the potential for dangerous interactions between classical MAOIs and tricyclic antidepressants was based on extensive literature and is clearly endorsed by the product information for the drugs in question.

All prescribing must maintain a balance between efficacy and safety. In the case of combination antidepressants, there is no objective evidence of benefit and good evidence of potential for harm. The purpose of my article was to suggest that moclobemide, although both a selective and reversible MAOI, is not necessarily safe in combination with other antidepressants. Dr Gillman appears to agree with me!

Associate Professor J.W.G. Tiller, the author of the article on the new antidepressants, comments:

There is extensive data on TCA-MAOI interactions which can be serious and fatal. Data on increased efficacy (if any) with drug combinations are, in contrast, scant. Such data usually do not compare the use of one or the other drug, in higher dosage, with the combination. Moclobemide is a reversible selective inhibitor of MAO-A with a short half -life, and clinically quite different to traditional MAOIs. Combination antidepressant treatment with moclobemide is not recommended but research data suggest that it may be used with other antidepressants in low dosage. This would normally be in the context of changing from one antidepressant to another as the former drug is washed out. Moclobemide and clomipramine co-prescribing is contraindicated.

The advent of a wide range of new drugs and a better understanding of augmentation strategies with lithium and anticonvulsants has, for practical purposes, almost totally eliminated the need for combination antidepressant therapy.

P.K. Gillman

Psychiatrist, Mount Pleasant, Qld

G. Shenfield

J.W.G. Tiller