Letters to the Editor

(Aust Prescr 1994;17:28-9)

Letters, which may not necessarily be published in full, should be restricted to not more than 250 words. When relevant, comment on the letter is sought from the author. Due to production schedules, it is normally not possible to publish letters received in response to material appearing in a particular issue earlier than the second or third subsequent issue.

MAO inhibitors in psychiatry

Editor, — I would like to respond to Associate Professor Evans’ concluding remarks (Aust Prescr 1993;16:59-60) regarding the new reversible MAO-A inhibitor moclobemide. He suggests tricyclics (TCAs) should be ‘the treatment of first choice for most patients with major depressive disorder’ and that TCAs ‘are effective and safe when (my emphasis) used properly and we know (my emphasis) how to use them properly’. Hence, he suggests moclobemide occupies a second order or lesser status.

In 1990, 386 Australians (source: ABS) died by suicide by ingestion of solid and liquid substances. A Brisbane survey of overdose fatalities1 suggests that TCAs account for about 10% of these suicides (i.e. 10% of 386). Hence, TCAs kill about 38 Australians a year by overdosage alone. Professor Evans gives brief mention of the overdose issue which does not do justice to this mortality nor the reality that depression is associated with more than 50% of all suicides (all methods). Saying that TCAs are ‘safe when used properly’ reminds me of the outmoded attitudes of the motor vehicle industry – that cars are safe when driven properly! Also, we do not know how to use TCAs properly for the simple reason that the ability of psychiatrists (not to mention others) to predict which patients will overdose is dismal.

I suggest that in considering which antidepressants to use, the potential for overdose is a vital consideration. As we cannot reliably predict suicide, I advocate that the newer less toxic antidepressants should be first-line drugs in patients at significant risk. I say this acknowledging the hazard of the unknown associated with new drugs (e.g. zimelidine and nomifensine – ‘new’ antidepressants which were subsequently withdrawn). In my opinion, tricyclics generally may be first-line drugs in those patients who one is confident will not overdose.

Dr Chris Cantor
Suicide Research and Prevention Program
Princess Alexandra Hospital
Woolloongabba, Qld

R E F E R E N C E

1. Cantor CH. Substances involved in fatal drug overdoses in Brisbane, 1979-1987. Acta Psychiatr Scand 1989;80(354 Suppl):69S-71S.

Associate Professor L. Evans, the author of the article, comments:
As I understand it, Dr Cantor is critical of my opinion that the tricyclics are still the first treatment of choice for major depressive disorder. The argument is that approximately 35 people per year kill themselves with tricyclics in Australia. I’m pleased he has made this argument as it is being put to doctors to suggest that they prescribe the newer and certainly much more expensive antidepressants instead of the older cheaper tricyclics. However, there is good evidence to show that removing a drug or particularly noxious agent which is popular as a means of suicide does not cut down the suicide rate. What it does do is transfer those who wish to kill themselves to some other means of doing so. In Britain the suicide rate dropped with the introduction of the tricyclic antidepressants, but did not decrease at the time the barbiturates were withdrawn and the benzodiazepines introduced. To use the motor vehicle analogy, restricting tricyclics would be as logical as preventing depressed people having access to car keys, as we know the car to be the means of suicide for many, or to prevent them from going into supermarkets or chemist shops which abound with drugs which can be fatal.

I am not sure that Dr Cantor is right about the newer antidepressants being less toxic in overdose, although I hope he is. I commented that drugs should be viewed with suspicion as to their lethality in overdose until their toxicity is known. For example, it took quite a long time for the evidence of the lethality of paracetamol in overdose to emerge. In my view, the real concern about the lethality of drugs and their prescription relates to people who have easy access to medications commonly used for minor sedative or analgesic purposes who may then take them impulsively at times of crisis without actually intending suicide or even self-harm. Relating this to the tricyclics reinforces the view that they should not be prescribed indiscriminately, particularly as night sedation, not that they shouldn’t be used as inferred by Dr Cantor.

MAO inhibitors

Editor, — Dietary restrictions are needed for combination therapy with selegiline and moclobemide.

Professor D. Story’s article (Aust Prescr 1993;16:54-7) on selective monoamine oxidase (MAO) inhibitors states that the reversible (selective) MAO-A inhibitors are less likely than older MAO inhibitors to cause dangerous adverse effects arising from their interaction with sympathomimetic amines. MAO-B inhibitors, despite MAO-B predominance in the liver, do not appear to be associated with the interaction with indirectly-acting sympathomimetics.

While there is no need for a low tyramine diet with these drugs when used separately in recommended doses, dietary tyramine can cause a hypertensive reaction when MAO-A and B inhibitors are prescribed concurrently. The mechanism for this observed interaction is not understood.

Patients being treated with both moclobemide (for depression) and selegiline (for Parkinson’s disease) should be on a low tyramine diet. The patient should also be aware of the potential for drug interactions as with irreversible, non-selective MAO inhibitors.

J.W.G. Tiller
Department of Psychiatry
University of Melbourne
Melbourne, Vic.

Editor, — A good review of the clinical usefulness of MAO inhibitors, such as that of David Story (Aust Prescr 1993;16:54-7) in relation to the new reversible drugs, is always welcome; especially since so much of what has been written in articles and textbooks in the past has been misleading or unhelpful.

I would like to add one or two small comments. I think it is preferable for the word ‘dangerous’ to be avoided when talking about the problems, especially the hypertensive reaction to tyramine, caused by MAO inhibitors. I did a calculation some years ago that suggested NSAIDs produced a much greater risk of morbidity and mortality than MAO inhibitors. If one takes into account the fact that NSAIDs are not given for a life-threatening condition, then one can see everything in a more objective and useful perspective. Although the cheese reaction is much talked about, the actual mortality relative to the high risk of suicide in severely ill, depressed patients is extremely small. If one considers the risk benefit ratio of other drugs, it would be logical to extend the use of the word ‘dangerous’, with an appropriate qualifying superlative, to many other drugs prescribed on a daily basis. This would be highly undesirable, if only from a medico-legal point of view.

The selectivity of these drugs is relative. Moclobemide (300-600 mg daily) gives a 30% inhibition of MAO-B. The extent to which its various active metabolites are selective is difficult to ascertain from the current literature. Selectivity is further diminished when higher doses are used. Indeed, the whole concept of selectivity may be quixotic.

P.K. Gillman
Psychiatrist
Mackay, Qld

Supply of beta agonist bronchodilators

Editor, — In his letter about ‘Regular inhaled beta agonist drug therapy’ (Aust Prescr 1993;16:53), Dr R. Munro Ford expresses concern about pharmacists supplying beta agonist bronchodilators ‘to anybody who wants them, whether they have asthma or not’. Such supply would be illegal in Tasmania under the Poisons Regulations 1975, which allow the pharmacist to supply Schedule 3 substances either on prescription or if ‘on consideration of the condition, disease or symptoms of the person (he) forms the opinion that the use of that substance in the treatment of the patient is justified’.

In the case of beta agonist inhalers, pharmacists have been directed to supply only continuation therapy to patients whose condition has been diagnosed by a medical practitioner, and to follow the National Asthma Campaign Guidelines. The suggestion by Dr Munro Ford that supply of beta agonist bronchodilators by pharmacists is unregulated is not correct.

John Galloway
Chief Pharmacist
for Kim Boyer
State Program Co-ordinator, Population Health
Community and Health Services
Hobart, Tas.

Editor, — I would like to write in reply to Dr R. Munro Ford who was staggered by the non-ratification of the restriction of inhaled beta agonists to prescription only. His statement of the spectacle of pharmacists selling these drugs to anybody who wants them displays a lack of understanding of pharmacists’ statutory responsibilities, particularly in Victoria.

Pharmacists are currently being disciplined and indeed fined for non-compliance with the Pharmacy Board directions for counselling patients on such matters.

There are virtually no circumstances when a beta agonist would be sold over-the-counter for purposes other than continuing treatment initiated by a medical practitioner. Indeed, in my pharmacy, it is not uncommon for a refusal to be made and the patient referred to the doctor for accompanying preventive medication where either overuse is discovered, or the doctor failed to initiate appropriate therapy. I must also report that the sales of beta agonists have thus fallen in my pharmacy, while the sales of inhaled steroids have dramatically increased. Nowadays we do not see very many patients who are misusing their beta agonist inhaler.

G. Blackman
Pharmacist
Bennettswood, Vic.

Editorial note: Although most metered dose aerosol preparations of beta agonists are scheduled as S3 items, pharmacists may have to meet additional requirements before dispensing. These requirements vary from State to State.

Antiviral drugs

Editor, — The two recent articles on antiviral drugs were excellent – ‘Antiviral drugs – mechanisms of action’ by S. Locarnini (Aust Prescr 1993;16:78-81) and ‘Antiviral drugs – clinical applications’ by A.C. Street (Aust Prescr 1993;16:81-6). However, I felt that
Dr Street’s judgement that topical acyclovir (5% aqueous cream – which is unavailable in Australia) for orolabial and genital herpes simplex virus (HSV) infections had no clinical efficacy was a little harsh. I agree that it seems that the benefit of topical acyclovir for orolabial and recurrent genital HSV infections in immunocompetent patients is limited to a reduction in viral shedding. However, topical acyclovir may have a role in primary genital herpes in immunocompetent hosts. It reduces the duration of the lesions, but has minimal efficacy in reducing new vesicle formation.1,2

In immunocompromised patients with mucocutaneous HSV disease, topical therapy also results in a significant reduction in the period of pain and healing of lesions.3,4

Topical therapy may have an effective clinical application in the management of primary genital HSV infection, and minor mucocutaneous HSV infections in immunocompromised patients.5

Len Moaven
Virology Registrar
ICPMR
Westmead Hospital
Westmead, N.S.W.

R E F E R E N C E S
1. Fiddian AP, Kinghorn GR, Goldmeier D, Rees E, Rodin P, Thin RN, et al. Topical acyclovir in the treatment of genital herpes: a
comparison with systemic therapy. J Antimicrob Chemother 1983;12(B Suppl):67S-77S.
2. Corey L, Nahmias AJ, Guinan ME, Benedetti JK, Critchlow CW, Holmes KK. A trial of topical acyclovir in genital herpes simplex virus infections. N Engl J Med 1982;306:1313-9.
3. Whitley R, Barton N, Collins E, et al. Mucocutaneous herpes simplex virus infections in immunocompromised patients: a model for evaluation of topical antiviral agents. Am J Med 1982;
73:236-40.
4. Whitley RJ, Levin M, Barton N, Hershey BJ, Davis G, Keeney RE, et al. Infections caused by herpes simplex virus in the immunocompromised host: natural history and topical acyclovir therapy. J Infect Dis 1984;150:323-9.
5. Whitley RJ, Gnann JW Jr. Acyclovir: a decade later. N Engl J Med 1992;327:782-9.

Dr A. Street, the author of the article, comments:
There are two topical acyclovir preparations. The 3% acyclovir ointment is used for the treatment of herpetic conjunctivitis and keratitis. A 5% preparation, formulated as an ointment or aqueous cream, is available in the U.S.A. and Europe, but not in Australia.

Although topical 5% acyclovir provides some clinical benefit for patients with primary genital herpes, oral acyclovir is significantly more effective and is the treatment of choice.1 Topical acyclovir is ineffective for recurrent genital herpes.2

Dr Moaven also notes that topical acyclovir has been reported to be effective in immunocompromised patients with limited mucocutaneous disease. However, since oral therapy is superior to topical therapy in immunocompetent individuals, it seems unwise to rely on topical treatment for a group of patients in whom herpetic infections are generally more severe and frequent.

The available evidence shows that topical acyclovir is less effective than systemic therapy and thus has little clinical role at present, except for treatment of herpes simplex eye infections.

R E F E R E N C E S
1. Corey L, Benedetti J, Critchlow C, Mertz G, Douglas J, Fife K, et al. Treatment of primary first episode genital herpes simplex virus infections with acyclovir: results of topical, intravenous and topical therapy. J Antimicrob Chemother 1983;12(B Suppl):79S-88S.
2. Luby JP, Gnann JW Jr, Alexander WJ, Hatcher VA,
Friedman-Kien AE, Klein RJ, et al. A collaborative study of patient-initiated treatment of recurrent genital herpes with topical acyclovir or placebo. J Infect Dis 1984;150:1-6.