(Aust Prescr 2008;31:115-8)
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.
Editor, – While Mark Ragg (Aust Prescr 2008;31:60–2) is technically correct in saying that most people quit by themselves1, he overlooks the more important point that the unaided quit rate is around 5–7%.2 It is not surprising that quitting is so difficult. Nicotine addiction is a chronic relapsing condition with a relapse curve that resembles that for heroin addiction.3 Popularity of strategy should not be confused with likelihood of success.
Most smokers find it very difficult to quit and are reluctant to seek help.4 It is difficult to capture the true natural history of smoking cessation in a study.1 Studies that have done so show that less than 2% of smokers quit per year.5 On average, smokers make between five and eight attempts before they are successful despite expressing strong interest in quitting.6
In a survey, 92% of smokers used only one strategy to quit.1 The majority of published evidence recommends the use of a combination of strategies that include some form of pharmacotherapy if nicotine dependent, referral to a proactive callback program like the Quitline, enlisting support, and addressing motivation and confidence.7,8,9,10 This is reflected in a reduction in the numbers needed to treat as selected strategies are combined. For example, eight smokers need to be treated with varenicline and supportive counselling to get one long-term quitter. Smokers shouldn't have to 'go it alone'. Health professionals should help them to increase their chance of success.
John Litt
Department of General Practice
Flinders University
Adelaide
References
- Doran CM, Valenti L, Robinson M, Britt H, Mattick RP. Smoking status of Australian general practice patients and their attempts to quit. Addict Behav 2006;31:758-66.
- Baillie AJ, Mattick RP, Hall W. Quitting smoking: estimation by meta-analysis of the rate of unaided smoking cessation. Aust J Public Health 1995;19:129-31.
- Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 2004;99:29-38.
- Carter S, Borland R, Chapman S. Finding the strength to kill your best friend: smokers talk about smoking and quitting. Sydney: Australian Smoking Cessation Consortium and GlaxoSmithKline Consumer Healthcare; 2001.
- Tobacco Advisory Group, Royal College of Physicians. Nicotine addiction in Britain. London: Royal College of Physicians of London; 2000.
- Piasecki TM. Relapse to smoking. Clin Psychol Rev 2006;26:196-215.
- National Institute for Health and Clinical Excellence (NICE). Brief interventions and referral for smoking cessation in primary care and other settings. London: NICE; 2006.
- Wu P, Wilson K, Dimoulas P, Mills EJ. Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. BMC Public Health 2006;6:300.
- International Primary Care Respiratory Group. Tackling the smoking epidemic. IPCRG International Guidance on smoking cessation in primary care. Aberdeen, Scotland: IPCRG; 2007.
- Zwar N, Richmond R, Borland R, Peters M, Stillman S, Litt J, et al. Smoking cessation pharmacotherapy: an update for health professionals. Melbourne: Royal Australian College of General Practitioners; 2007.
Editor, – I read with great interest the target ranges for digoxin interactions in Table 1 of the article on therapeutic drug monitoring (Aust Prescr 2008;31:42–4). The issue of the therapeutic range for digoxin is perhaps a controversial one these days, but the author should certainly be given an opportunity to explain the 'range', particularly because of recent analyses of mortality data in trials of digoxin.
Perhaps a suitable correction as well as clarification would be in order?
John D Horowitz
Head of Cardiology
The University of Adelaide
Dr Ghiculescu, author of the article, comments:
The Digitalis Investigation Group found that digoxin reduced hospitalisations, but did not reduce overall mortality in heart failure when the target for the therapeutic range was 0.5–2 nanogram/mL.1 Post hoc analysis of this trial found that mortality and hospitalisations were reduced if the serum digoxin was 0.5–0.9 nanogram/mL. Concentrations greater than 1 nanogram/mL were associated with higher mortality.2 A concentration less than 1 nanogram/mL equates to less than 1 microgram/L. The currently recommended therapeutic range is therefore 0.5–0.9 nanogram/mL.
It has been suggested that an even lower concentration, less than 1 nanogram/dL, be used in patients with symptomatic systolic left ventricular failure.3 That equates to 10 nanogram/L which is 0.01 microgram/L. This is significantly lower than the range used in the digoxin trial. However, this low concentration cannot easily be measured.
References
- The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-33.
- Ahmed A, Rich MW, Love TE, Lloyd-Jones DM, Aban IB, Colucci WS, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006;27:178-86.
- Chatterjee K. Congestive heart failure: what should be the initial therapy and why? Am J Cardiovasc Drugs 2002;2:1-6.
Editor, – May I congratulate Amy McLean on her article regarding bronchiectasis (Aust Prescr 2008;31:77–9). She gave a concise and practical approach to strategies often employed in treatment. May I also support the Editor in publishing this article, considering many of the drugs listed and regimens suggested were 'off label' and certainly not supported as subsidised medicines for these indications on the Pharmaceutical Benefits Schedule.
Unfortunately, many such prescriptions are unavailable to doctors who practise outside of major metropolitan teaching hospitals, although the novel approaches with nebulised aminoglycosides and longer term use of macrolides are certainly used by us, the 'respiratory colleagues'. There was also no mention made of colistin, which from experience is expensive to source, and intravenous gammaglobulin used monthly that has proven effective, particularly in those with subclass immunoglobulin deficiency.
Rob Campagnaro
Respiratory and General Physician
Bendigo, Vic.
Editor, – There are significant problems with the use of literature to support the statements in the article by Dr Singh and Professor Berk on acute management of bipolar disorders (Aust Prescr 2008;31:73–6). The authors have generalised from bipolar I disorder to bipolar II disorder and from severely ill tertiary-treated bipolar I patients to the broader population of patients with bipolar disorder. They have also misrepresented the risk of suicide and the relationship between medication status and relapse risk.
According to the article, 'sufferers spend 32–50% of follow-up in depressive states and only 1–9% in elevated states'. However, the source cited focused on bipolar I disorder and cautioned that 'Generalization to other samples of BP-I may be limited because the CDS cohort consisted of severely ill, tertiary care, white patients'.1 Inappropriately generalising biased samples contributes to the clinician's illusion2, which distorts perceptions of chronicity and severity.
The article claimed that over 90% of patients with bipolar disorders relapse without medications. However, in the source cited the relapse rate applied specifically to bipolar I disorder.3 The implication that relapse occurs only without medication ignores a large body of evidence that it frequently occurs with medication.4,5,6,7 The use of psychotropic drugs between episodes is not associated with time to relapse or recurrence.8
The statement that 15% of people with bipolar disorders die by suicide is based on pharmaceutical industry funded grey literature.9 Australian empirical evidence was lacking in this citation and relied on an article by Goodwin and Jamison.10 Later, Jamison acknowledged that the quoted risk of 15% may have been too high.11 The inflated risk was based largely on inpatient samples, inappropriately generalised to the broader population.
The article largely ignored the value of psychological interventions. There is strong evidence that these are effective in the prevention of relapse. Despite emphasising the destabilisation potential of antidepressants, the authors do not mention the potential adverse effects of antipsychotics and other drugs for bipolar episodes. These include obesity, diabetes, metabolic syndrome and dyslipidaemia.12
These problems with the article exaggerate both the severity of bipolar disorders and the value of medications, while devaluing psychological treatments.
Melissa Raven
Adjunct Lecturer, Department of Public Health
Flinders University, Adelaide
References
- Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002;59:530-7.
- Cohen P, Cohen J. The clinician's illusion. Arch Gen Psychiatry 1984;41:1178-82.
- American Psychiatric Association. Diagnostic and statistical manual of mental disorders 4th ed. Text revision. DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.
- Morriss RK, Faizal MA, Jones AP, Williamson PR, Bolton C, McCarthy JP. Interventions for helping people recognise early signs of recurrence in bipolar disorder. Cochrane Database of Systematic Reviews 2007, Issue 1. Art No.:CD004854. DOI: 10.1002/14651858. CD004854. pub2.
- Lam DH, Watkins ER, Hayward P, Bright J, Wright K, Kerr N, et al. A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder: outcome of the first year. Arch Gen Psychiatry 2003;60:145-52.
- Tohen M, Chengappa KN, Suppes T, Baker RW, Zarate CA, Bowden CL, et al. Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone. Br J Psychiatry 2004;184:337-45.
- Healy D. The latest mania: selling bipolar disorder. PLoS Med 2006;3:e185. Epub 2006 Apr 11.
- Judd LL, Schettler PJ, Akiskal HS, Coryell W, Leon AC, Maser JD, et al. Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Arch Gen Psychiatry 2008;65:386-94.
- Access Economics. Bipolar disorder: costs. An analysis of the burden of bipolar disorder and related suicide in Australia. Melbourne: Access Economics, for SANE Australia; 2003.
- Goodwin FK, Jamison KR. Manic-depressive illness. New York: Oxford University Press; 1990.
- Simpson SG, Jamison KR. The risk of suicide in patients with bipolar disorders. J Clin Psychiatry 1999;60 Suppl 2: 53-6, 75-6, 113-6.
- Yatham LN, Kennedy SH, O'Donovan C, Parikh SV, MacQueen G, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007. Bipolar Disord 2006;8:721-39.
Dr Ajeet Singh and Professor Michael Berk, authors of the article, comment:
Several issues are raised by the reader's correspondence. It needs to be stressed that the paper is based on the available, if imperfect, evidence base. Firstly, the validity of suicide risk estimates in bipolar disorders has been raised. A meta-analysis of studies on suicide risk in all psychiatric disorders found that the risk of suicide was about 15-fold for patients with index diagnosis bipolar disorder.1 In a 1–9 year follow-up study, 6% of bipolar I and 18% of bipolar II patients died by suicide.2 Based on six independent studies, the rate of suicide attempts is reported as 17% for bipolar I disorder and 24% for bipolar II disorder.3 Despite varying rates in the literature, the risk of suicide and self-harm in bipolar disorders is the major driver of mortality in the disorder, and needs to be one of the critical foci of treatment.
Secondly, while psychoeducation and cognitive behavioural therapy have an important place in relapse prevention in the maintenance phase, they have not been studied in the acute treatment of either mania or depression, and while we agree that they are of potential value, the absence of an evidence base precludes their inclusion in an evidence-based summary. Clinical trials of psychosocial treatments in the acute phase of the disorder, particularly in depression, are clearly a priority, given the limitations of available treatments.4,5 While healthy skepticism has an important role in evidence-based medicine, it is still necessary to be guided by the available data.
References
- Harris EC, Barraclough B. Suicide as an outcome for mental disorders. Br J Psychiatry 1997;170:205-28.
- Dunner DL, Gershon ES, Goodwin FK. Heritable factors in the severity of affective illness. Biol Psychiatry 1976;11:31-42.
- Rihmer Z, Kiss K. Bipolar disorders and suicidal behaviour. Bipolar Disord 2002;4 Suppl 1:21-5.
- Vieta E, Colom F. Psychological interventions in bipolar disorder: from wishful thinking to an evidence-based approach. Acta Psychiatr Scand Suppl 2004;422:34-8.
- Scott J, Colom F, Vieta E. A meta-analysis of relapse rates with adjunctive psychological therapies compared to usual psychiatric treatment for bipolar disorders. Int J Neuropsychopharmacol 2007;10:123-9.
Compounding in community pharmacy
Editor, – The editorial 'Compounding in community pharmacy' (Aust Prescr 2008;31:30–1) outlines concerns that regulators have with the activities of some 'compounding' pharmacists. Regulators are concerned with high-volume (bulk) compounding and the promotion of formulations that are not subject to the same regulations as are applied to the pharmaceutical industry. They do not appear to be concerned with single-unit extemporaneous dispensing of low-risk products.
While we agree that compounding practice standards are in need of review, we believe a risk-management approach should be followed. Uniform adoption of standards that may, for example, demand end-product testing would not seem practical, or necessary, for low-risk extemporaneously prepared products such as creams or lotions.
The prescribing of many compounded medicines is regarded as 'off label'. Consequently, prescribers and dispensers should be guided by contemporary standards for evaluating off-label prescribing.1 We believe the guidance for off-label prescribing should be extended for compounded medicines to include the risk-based evaluation and classification of the factors outlined in Table 1.
We suggest a code of practice in compounding which would include:
- establishing, assuring and maintaining quality through appropriate processes and documentation
- a risk-management approach (Table 1) to the evaluation of compounded medicines
- ensuring that prescribers and consumers have current, evidence-based information to support the quality use of compounded medicines
- complying with therapeutic goods advertising codes and legislation.
These risk-management approaches would support the role of pharmacists in compounding medicines to contemporary standards of quality, safety and efficacy within the spirit of Australia's National Medicines Policy.
Romano A Fois
Lecturer (Pharmaceutics)
Andrew J McLachlan
Professor of Pharmacy (Aged Care)
Barry T Mewes
Visiting Pharmacist
Iqbal Ramzan
Professor of Pharmacy and Dean
Faculty of Pharmacy
University of Sydney
Reference
- Gazarian M, Kelly M, McPhee JR, Graudins LV, Ward RL, Campbell TJ. Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Aust 2006;185:544-8.
