(Aust Prescr 1999;22:3-5)
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.
Antidepressant wash-out periods
Editor, - Your response to the letter from Julian Fidge (Aust Prescr 1998;21:60) supporting a 24-hour wash-out when changing from moclobemide to any selective serotonin reuptake inhibitor (SSRI) is in error in stating `There is no reference in the current Australian product information for any SSRI regarding interactions (if any) with reversible selective inhibitors of monoamine oxidase A in general, or moclobemide in particular'.The product information for sertraline (Zoloft) in the 1998 MIMS Annual specifically includes reversible MAOIs in recommending that `Zoloft should not be used in combination with an MAOI (sic) or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping Zoloft before starting an MAOI'.
Pfizer is the only company marketing SSRIs in Australia which specifically mentions reversible MAOIs in this context. The Psychotropic Drug Guidelines (Victorian Medical Postgraduate Foundation Therapeutics Committee) contradict the product information for sertraline by recommending a 24-hour wash-out period before changing from moclobemide to sertraline, a recommendation they extend to all other SSRIs. I think the issue is important, as a patient with serious depressive illness should not have an unnecessary 14-day wash-out if moclobemide has not been effective, and a SSRI is indicated.
David Grounds
Psychiatrist
Richmond, Vic.
Editor, - Thank you for the excellent `Serotonin states' table in the recent Australian Prescriber (1998;21:63), prepared by Dr J.W.G. Tiller.
I work at times in a psychiatric hospital, and serotonin syndrome is a concern for all the staff. In the table, you refer to MAOIs and SSRIs as being a risk for serotonin syndrome.
1. Do you include moclobemide (Aurorix) as a risk? There seems to be some confusion in various sponsors' recommendations about wash-out times. I read a report of a South Australian magistrate recommending that the product information for Aurorix be altered to warn of serotonin syndrome because someone had committed suicide with paroxetine plus a lot of moclobemide - hardly a recommended use. The implication is that the syndrome is a risk with moclobemide and selective serotonin reuptake inhibitors.
2. What about sumatriptan? Our local pharmacist has a friendly computer which keeps warning us about prescriptions for patients who are taking SSRIs and sumatriptan. The combination of migraine and depression is not uncommon, and the use of that combination of medicines is also not uncommon. Is it a real risk?
3. How about St. John's wort (sales are now exceeding SSRIs I think)? I heard that a case of serotonin syndrome had been reported. It might be about as valid as all the claims made for it on the Internet as a cure for everything from syphilis to sinusitis!
Alex Tahmindjis
Physician
Eastwood, N.S.W.
Professor J.W.G. Tiller, author of `Serotonin states', comments:
The letters from Dr Grounds and Dr Tahmindjis both raise important points.
Firstly, the most recent sertraline (Zoloft) product information reports an interaction with co-prescribed sertraline and moclobemide. It does not make recommendations regarding changing to or from moclobemide. It only refers to changes with MAOIs (non-selective irreversible inhibitors of monoamine oxidase). After moclobemide, 24-48 hours should be adequate before starting another agent. Sertraline, even from high doses, should be largely washed-out by 5-7 days when moclobemide or other antidepressants can be commenced. It is inappropriate to deny patients treatment because of excessive change-over times.
As moclobemide is a non-specific serotonin enhancer, as are most SSRIs, there is a general contraindication to co-prescribed sumatriptan, notwithstanding the fact that some patients have used the combination seemingly without adverse event. Prior good luck is no protection. Interaction data on St. John's wort are very limited, with different strengths and purities being used. As it is purported to affect serotonin, there may potentially be interactions with MAOIs, moclobemide, SSRIs and other serotonin active agents.
Editor, - In his letter regarding antidepressant wash-out periods (above), Dr D. Grounds correctly notes that the approved product information for sertraline (Zoloft) explicitly includes reversible MAOIs in the contraindication against use concurrently or within two weeks, and that the product information for the other SSRIs available in Australia are not so explicit.
The subsequent comment from Professor Tiller errs in fact in referring to the product information for Zoloft. The present wording of the contraindication (i.e. explicitly including moclobemide as well as the type-B selective MAOI, selegiline) was adopted in the latter part of 1995 and has remained unchanged since then.
Although we acknowledge that, in many cases, failure to observe this rule has been free of adverse consequences, individual cases have been reported which support Professor Tiller's subsequent comment about 'prior good luck', and we stand by the terms of the contraindication.
M.M. Lawrie
Director Medical Affairs
Pfizer Australia
West Ryde, N.S.W.
Sleep apnoea and delayed fracture healing
Editor, - I refer to the article on sleep studies (Aust Prescr 1998;21:40-3). One of my patients is a 40-year-old man with diagnosed sleep apnoea, but on no treatment. He has an undisplaced distal radial fracture involving the joint surface, diagnosed on bone scan. He had symptoms 12 months post-fracture and a positive bone scan 6 months post-injury. I understand that a bone scan can remain positive for some time post-fracture and is often a sign of healing. However, if his continuing symptoms are attributable to delayed healing, is sleep apnoea implicated and, as a follow-on, would treatment of the sleep apnoea assist the recovery?J. Azoury
General Practitioner
Queanbeyan, N.S.W.
Dr A.M. Southcott, the author of the article, comments:
Dr Azoury raises a very interesting question about sleep apnoea and delayed
fracture healing. Whilst I was unable to find any direct references linking
these two topics, there are some tantalising pieces of information which could
lead one to speculate on such a relationship. The first is the anabolic response
induced by growth hormone release from the pituitary gland, and the beneficial
effects of growth hormone administration in patients after surgery and trauma.1 The
second is the increasing awareness of the metabolic aspects of sleep apnoea.
In patients with severe sleep apnoea, levels of insulin-like growth factor-1,
a biological marker of growth hormone secretion, are reduced as are nocturnal
levels of growth hormone.2 Some patients with severe
sleep apnoea have levels similar to patients with growth hormone deficiency
which may have effects on bone and mineral metabolism and body composition.
It is thought that repetitive arousal due to sleep apnoea may impair the growth
hormone response to endogenous bursts of growth hormone releasing hormone.
Treatment of severe sleep apnoea results in increased secretion of growth hormone3 and
an increase in insulin-like growth factor-1 levels.4
It would be possible to speculate that in untreated severe sleep apnoea, fracture healing may be compromised due to a relative deficiency of growth hormone. As mentioned above, to my knowledge this has not been proven.
References
1. Revhaug A, Mjaaland M. Growth hormone and surgery. Horm Res 1993;40:99-101.
2. Grunstein RR. Metabolic aspects of sleep apnea. Sleep 1996;19 (10 Suppl):218S-220S.
3. Grunstein RR, Handelsman DJ, Stewart DA, Sullivan CE. Growth hormone secretion is increased by nasal CPAP treatment of sleep apnea. Am Rev Respir Dis 1993;147:A686.
4. Grunstein RR, Handelsman DJ, Lawrence SJ, Blackwell C, Caterson ID, Sullivan CE. Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. J Clin Endocrinol Metab 1989;68:352-8.
Editor, - I was interested to read Associate Professor R. Moulds' editorial `Quality use of medicines - where to next' (Aust Prescr 1998;21:58-9) about future directions in the quality use of medicines in Australia.The paper commenced with information about a symposium held during the ASCEPT meeting in December 1997, and then commented upon the future place in Australia of Australian Prescriber, the Therapeutic Guidelines and the Australian Medicines Handbook and their possible `coming together' in an electronic version.
Although it is reasonably apparent that Associate Professor Moulds is a member of the Executive Editorial Board of Australian Prescriber, I suggest that the editorial should have also noted that he is a member of the Management Committee of the Australian Medicines Handbook and Chairman of the writing committees of several of the Therapeutic Guidelines.
It is also unfortunate that it was unclear in the editorial whether these particular comments were the views of the author or reflected comments emerging from the symposium.
I suggest that any association of authors with the topics upon which they are commenting should be more clearly identified in future, to avoid allegations of conflict of interest, as they are in peer-reviewed journals.
This issue of Australian Prescriber also contained a presumably invited article by a U.K. clinician titled `When to use a new drug' (Aust Prescr 1998;21:67-9). It advises readers that `New alternatives to existing treatments should be used only if these bring additional benefits commensurate with their cost'. This is followed by a self-test question about the impact of pharmaceutical industry marketing strategies.
It seems that quite a few articles recently published in Australian Prescriber have been somewhat philosophical and have commented on the approach that `should' be adopted in medical practice in Australia.
Australian Prescriber terms itself `an independent review'. Perhaps the nature of that `independence' needs to be more transparent.
Janice E. Hirshorn
Director, Policy and Strategy Development
Australian Pharmaceutical Manufacturers Association
North Sydney, N.S.W.
Editor's note:
Australian Prescriber has a policy for authors to declare all conflicts
of interest. Editorials are peer-reviewed before publication in the same way
as articles.
Dental implications of warfarin therapy
Editor, - We wish to comment on the dental implications of warfarin therapy as discussed by Professor R. Woods (Aust Prescr 1998;21:79).We agree that there is little need to modify anticoagulant therapy for most routine dental treatment, but in procedures that are likely to cause significant bleeding, patient management may need to be changed.
We draw your readers' attention to a paper published in 1989.1 In this, they describe the safety and efficacy of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. We followed up their observations with a report confirming these findings.2 Our recommendation was that, for simple extractions, patients continue on their stable dose of warfarin and are given tranexamic acid mouthwash without interruption of their anticoagulant therapy. For more extensive surgery, we have ceased warfarin for up to 4-5 nights before the procedure and recommenced it on the evening of the procedure if the bleeding has been locally controlled. It is critical that excellent haemostasis is ensured at the time of dental surgery including the use of sealants and suturing.
We prescribed tranexamic acid as a 5% solution with 10 mL to be held in the mouth for two minutes 5 times/day for up to 7 days.
The use of oral tranexamic acid has revolutionised the dental management of patients on oral anticoagulants and is also useful in the oral medical management of patients with other bleeding disorders such as haemophilia and thrombocytopenia.
Associate Professor A. Street
Head, Haematology Unit
and
Dr W. Leung
Oral Surgeon, Dental Clinic
Alfred Hospital
Melbourne, Vic.
References
1. Sindet-Pedersen S, Ramstrom G, Bernvil S, Blomback M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989;320:840-3.
2. Street AM, Leung W. Use of tranexamic acid mouthwash in dental procedures in patients taking oral anticoagulants [letter]. Med J Aust 1990;153:630.
Professo
