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Managing patients with deliberate self harm who refuse treatment Education and debate p 905 in accident and emergency departments Advice and procedure require correction Editor—In their lesson of the week on managing patients with deliberate self harm who refuse treatment in the accident and emergency department Hassan et al recommend that doctors must be fully conversant with the law on assessing capacity to consent to treatment and its application.1 It is equally important in these difficult cases to be familiar with the application of the Mental Health Act 1983 or Mental Health (Scotland) Act 1984, which Hassan et al seem not to be. They state: “If the overdose is considered to be a consequence of a mental disorder then the patient can also be treated medically for the overdose under the terms of the Mental Health Act.” This statement is reiterated in their proposed algorithm, recommended for use at accident and emergency departments. This is simply not the case. The Mental Health Act is for the treatment of mental disorders. It does not authorise the treatment of a physical disorder even if it arises as a consequence of a mental disorder. Therefore the Mental Health Act is of no help in the immediate medical management of patients presenting
Advice to authors We prefer to receive all responses electronically, sent either directly to our website or to the editorial office as email or on a disk. Processing your letter will be delayed unless it arrives in an electronic form. We are now posting all direct submissions to our website within 24 hours of receipt and our intention is to post all other electronic submissions there as well. All responses will be eligible for publication in the paper journal. Responses should be under 400 words and relate to articles published in the preceding month. They should include 20 weeks, and induced abortions after prenatal diagnosis of malformations. During 1990-4 there were 13 registries following strict Eurocat methodology and where induced abortion after prenatal diagnosis of congenital malformations was noted. The 13 registries covered 1 284 599 births. For this period the contribution of induced abortion in the registries ranged from 4.0-7.6 per 1000 births in the three French registries to 0.7-3.1 per 1000 births in the other European countries.2 The table shows the proportion of induced abortion among cases of major congenital malformations. If studies concerning risk factors during pregnancy include only information
Selected major congenital malformations detectable by prenatal ultrasound investigation (data from 13 Eurocat registries 1990-42)
No of cases
No (%) of induced abortions
Anencephalus
447
375 (84)
Spina bifida
639
275 (43)
Hypoplastic left heart
316
80 (25)
Omphalocele
334
139 (42)
Bilateral renal agenesis
250
129 (52)
from live births and stillbirths they will miss the large number of cases diagnosed prenatally in which termination of pregnancy is subsequently carried out. This is not discussed in the paper.1 In studies from the 1970s and ’80s the problem is of only minor importance. For future studies of risk assessments during pregnancy it is important also to include terminations of pregnancies. These terminations often occur in the more severe cases, and prenatal diagnostic methods are more often performed in risk pregnancies, in anxious mothers taking benzodiazepines, and in mothers with epilepsy. If only live births are studied the conclusions might be wrong because today live births occur in a selected group of all pregnancies. Ester Game specialist in paediatrics Eurocat, University of Southern Denmark, 5000 Odense C, Denmark Ulf Bergman visiting professor Department of Clinical Pharmacology, University of Southern Denmark 1 Dolovich L, Addis A, Vaillancourt JMR, Power JDB, Koren G, Einarson TR. Benzodiazepine use in pregnancy and major malformations or oral clefts: meta-analysis of cohort and case-control studies. BMJ 1998;317:839-43. (26 September 1998.) 2 Eurocat Working Group. Eurocat report 7. Brussels: Scientific Institute of Public Health–Louis Pasteur, 1997.
Pooled results are sensitive to zero transformation used Editor—In 1994 Shapiro suggested that meta-analysis to combine the results of observational studies should be abandoned because the individual studies are open to particular bias related to their study design.1 Dolovich et al have reported their metaanalysis of the use of benzodiazepines during the first trimester of pregnancy and the risk of oral clefts or major congenital malformations.2 The differences they found between the results of the cohort and case-control studies suggest that it may be bias that is being pooled rather than true effects. The authors themselves express reservations that most cases reported were derived from only three studies, so have the patients with oral cleft been counted more than once in the pooling process? The statistical method used in this paper cannot be relied on, as the pooled results are sensitive to the adjustment made for trials in which the number of malformations was zero. For example, the largest cohort study (that by Bergman et al, 1992) is calculated as showing an odds ratio of 1.21, based on 0/1354 exposed patients having oral cleft BMJ VOLUME 319
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Letters compared with 62/102 985 not exposed. This result suggests that the zeros have been adjusted to 1 for the calculation (as odds of zero cannot be turned into an odds ratio). If the zero was counted as 0.5, however, the odds ratio for the study would fall to 0.61. Even more bizarre is the study of epileptic patients (that by Robert et al, 1986), in which 0/4 compared with 1/144 is transformed into an odds ratio of 10.63 on the basis of the zero transformation. Surely 0/4 is exactly the expected finding if the odds ratio was 1 and there was no difference between the exposed and non-exposed groups. This paper seems to lend weight to Shapiro’s suggestion that meta-analysis should be confined to controlled clinical trials. Christopher Cates general practitioner Bushey, Hertfordshire WD2 2NN
[email protected] 1 Shapiro S. Meta-analysis/Schmeta-analysis. Am J Epidemiol 1994;140:771-7. 2 Dolovich L, Addis A, Vaillancourt JMR, Power JDB, Koren G, Einarson TR. Benzodiazepine use in pregnancy and major malformations or oral clefts: meta-analysis of cohort and case-control studies. BMJ 1998;317:839-43. (26 September 1998.)
Quality of primary studies must influence inferences made from meta-analyses Editor—In a meta-analysis of cohort and case-control studies on the association of malformations with use of benzodiazepines in pregnancy, Dolovich et al recommend the use of antenatal diagnostic tools for detecting malformations in clinical practice.1 For future research they say that further case-control studies are needed. They have disregarded the importance of the quality of primary studies in arriving at these conclusions. In their analysis Dolovich et al stratify pooling of data according to the quality of the study. Higher quality studies (cohort studies) showed lack of an association, while poor quality studies (case-control studies) showed an association. This is apparent from the graphic presentation of odds ratios in the paper. To emphasise this point we have performed logistic regression analysis, with fetal malformation (both major malformation and oral cleft) as the binary dependent variable. A logistic model was built to assess the impact of the quality of the study on the strength of the association between exposure to benzodiazepines and malformation. The value of the coefficient for the interaction term between “study quality” (cohort v case-control) and “exposure” (exposure v non-exposure) provided an estimate of the bias in poor quality studies.2 Our analysis showed that the case-control studies exaggerated the estimate of the odds ratio for the association between malformation and exposure to benzodiazepines by 55% (95% confidence interval 28% to 72%, P = 0.0006) compared with cohort studies. It has been well established that poorer quality literature tends to exaggerate the estimate of the strength of an association, and in this circumstance it is more appropriate to base inferences on higher BMJ VOLUME 319
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quality evidence.3 Our conclusion on the basis of meta-analysis of higher quality evidence is that there is no association between maternal exposure to benzodiazepines and fetal malformation; further research should aim at generating high quality evidence in the form of cohort studies rather than case-control studies. Khalid S Khan lecturer
[email protected] Catherine Wykes specialist registrar Harry Gee consultant Department of Obstetrics and Gynaecology, Birmingham Women’s Hospital, Birmingham B15 7TG 1 Dolovich LR, Addis A, Vaillancourt JMR, Power JDB, Koren G, Einarson TR. Benzodiazepine use in pregnancy and major malformation or oral cleft: meta-analysis of cohort and case-control studies. BMJ 1998;317:839-43. (26 September 1998.) 2 Khan KS, Daya S, Collins JA, Walter SD. Empirical evidence of bias in infertility research: overestimation of treatment effect in crossover trials using pregnancy as the outcome measure. Fertil Steril 1996;65:939-45. 3 Khan KS, Daya S, Jadad AR. The importance of quality of primary studies in producing unbiased systematic reviews. Arch Intern Med 1996;156:661-6.
Vascular anomalies must be properly classified Editor—Zameel Cader and Winer’s lesson of the week highlighted a common error of terminology in describing vascular anomalies.1 The term cavernous haemangioma is a confusing one and should ideally be avoided. The classification of vascular anomalies by Mulliken and Glowacki successfully categorised vascular anomalies in a consistent and meaningful way according to their endothelial cell characteristics.2 The classification distinguishes haemangiomas from vascular malformations. A haemangioma is characterised histologically by high endothelial cell turnover and in addition has a specific and characteristic clinical “life cycle”—strawberry naevus.3 All other lesions are vascular malformations, which have normal endothelial cell turnover with abnormal gross vascular anatomy and are further subdivided into low flow and high flow lesions. Low flow lesions include capillary, lymphatic, and venous lesions or combinations of these, whereas high flow lesions include the arteriovenous malformations.
In the past the term cavernous haemangioma has been indiscriminately assigned to all categories of vascular anomalies.4 The table shows that each category not only has a different clinical course but also has different treatment options. Good classifications are important for categorising information, recording it, yielding prognostic information, and ultimately guiding treatment plans.5 The Mulliken and Glowacki classification helps in this way and should consequently be adhered to when vascular anomalies are referred to. It is our duty as clinicians to be consistent in our terminology in order to be able to communicate effectively, to promote research, and to develop therapeutic strategies. Patrick Mallucci head and neck fellow Royal Brisbane Hospital, Brisbane, Australia
[email protected] 1 Zameel Cader M, Winer JB. Cavernous haemangioma mimicking multiple sclerosis. BMJ 1999;318:1604-5. (12 June.) 2 Mulliken JB, Glowacki J. Haemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg 1982;69:412. 3 Pasyk KA, Cherry GW, Grabb WC, Sasaki GH. Quantitative evaluation of mast cells in cellularly dynamic and adynamic vascular malformations. Plast Reconstr Surg 1984;73:69-77. 4 Kane WJ, Morris S, Jackson IT, Woods JE. Significant haemangiomas and vascular malformations of the head and neck: clinical management and treatment outcomes. Ann Plast Surg 1995;35:133-43. 5 Kaban LB, Mulliken JB. Vascular anomalies of the maxillofacial region. J Oral Maxillofac Surg 1986;44:203-13.
Choosing the right antibiotic Right drug at right time in right dose saves lives Editor—Leibovici et al make a fundamental point about the prescription of antimicrobial drugs—the right antibiotic at the right time saves lives1—and we should not forget it. Yet as the various commentators point out, it is not always easy to choose the right antimicrobial since we know that all drugs have side effects, some are expensive, and some are more poisonous than others. In intensive care, many patients present with septic shock, and we usually only get “one bite” at the cherry. I try to teach our residents a few of the “see-saw” principles of antimicrobial prescribing that I have learnt along the way.
Classification distinguishing haemangiomas from vascular malformations Haemangioma
Vascular malformation
Histology
High endothelial cell turnover
Normal endothelial cell turnover
Presence at birth
Usually absent
Present (not always apparent clinically)
Clinical course
Apparent by 6-8 weeks after birth, proliferative phase for 1-2 years, followed by spontaneous involution (majority)
Tends to grow in proportion with person throughout life
Diagnosis
Clinical history + appearance
Vascular imaging Magnetic resonance angiography, Doppler ultrasonography, angiography
Treatment options
Normally treated by observation only If not involuted fully, minor surgical correction If very large or in anatomically sensitive area, systemic or intralesional steroids or interferon gamma or surgical correction
Low flow lesions: Depending on site, size, symptoms, etc, from conservative only to laser for capillary malformations, sclerotherapy with or without excision, or surgery alone High flow lesions: Depending on site, size, and stage, from conservative alone to embolisation plus surgery or surgery alone
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David Bihari associate professor Intensive Care Unit, St George Hospital, Sydney NSW 2217
[email protected] 1 Leibovici L, Shraga I, Andreassen S. How do you choose antibiotic treatment? [with commentaries by Pauker SG, Rothberg M, Weinberg JR, Duerden BI, and Drickamer MA] BMJ 1999;318:1614-8 (12 June.)
Antibiotic choice may affect risk of Clostridium difficile infection Editor—It is surprising that neither Leibovici et al nor the commentaries mention the issue of infection with Clostridium difficile induced by antibiotics when discussing the appropriateness of antimicrobial treatment of a severe urinary tract infection in a 83 year old man.1 Despite evidence of underreporting,2 notifications of C difficile continue to increase in England and Wales. Over 17 000 predominantly hospital acquired cases were reported to the Communicable Disease Surveillance Centre in 1998, 80% of which were in elderly people. Cephalosporins such as cefuroxime and cefotaxime have been widely cited as predisposing to C difficile infection. Leibovici et al consider cephalosporins but not fluoroquinolones such as ciprofloxacin or ureidopenicillins for the empirical treatment of severe sepsis. Aminoglycosides, fluoroquinolones, and ureidopenicillins have a lower propensity to induce C difficile infection.3 A prospective, crossover study in a geriatric ward found that empirical treatment with piperacillin-tazobactam was seven times less likely to induce C difficile infection than was treatment with cefotaxime.4 The proportion of British hospitals reporting a change in antibiotic policies due to C difficile infection increased from 5% to 20% between 1993 and 1996.2 Elderly patients with nosocomial C difficile infection stay a median of three weeks longer in hospital, two weeks of which is spent in scarce isolation facilities, and a case-control study found an excess cost of over £4000 per case.5 Such costs dwarf those associated with buying antibiotics and cannot be ignored in cost effectiveness analyses of antimicrobial treatment. Care must be taken when extrapolating average gains in studies to specific patients. Leibovici et al1 refer to data derived from patients with a median age of 72 years and hospital or community acquired bacteraemia 920
or fungaemia. Outcome in an 82 year old man with community acquired urinary tract infection may well differ from these findings. The authors also give antibiotic susceptibility rates for bacteraemic isolates, which include community and hospital pathogens, thus biasing towards resistant strains. Presumably, the figure of 77% susceptibility to gentamicin includes Gram positive and Gram negative isolates; community acquired Gram negative isolates are likely to be more susceptible to gentamicin. Once daily gentamicin may be associated with lower nephrotoxicity and in combination with ampicillin would be a potential therapeutic choice. The choice of antibiotic is complex. Workable antibiotic policies should aim to guide optimal treatment but will inevitably contain compromises and assumptions, not least because locally applicable and patient specific data are rarely available. Although “appropriate” antimicrobial treatment is a laudable goal, side effects cannot be relegated to secondary considerations. Mark H Wilcox senior lecturer
[email protected] Jon Sandoe specialist registrar Department of Microbiology, General Infirmary and University of Leeds, Leeds LS1 3EX 1 Leibovici L, Shraga I, Andreassen S. How do you choose antibiotic treatment? [with commentaries by Pauker SG, Rothberg M, Weinberg JR, Duerden BI, and Drickamer MA] BMJ 1999;318:1614-8. (12 June). 2 Wilcox MH, Smyth ET. Incidence and impact of Clostridium difficile infection in the UK, 1993-1996. J Hosp Infect 1998;39:181-7. 3 Anand A, Bashey B, Mir T, Glatt AE. Epidemiology, clinical manifestations, and outcome of Clostridium difficile diarrhea. Am J Gastroenterol 1994;89:519-23. 4 Settle CD, Wilcox MH, Fawley WN, Corrado OJ, Hawkey PM. Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin-tazobactam. Alimentary Pharmacol Therapeutics 1998;12:1217-23. 5 Wilcox MH, Cunniffe JG, Trundle C, Redpath C. Financial burden of hospital-acquired Clostridium difficile infection. J Hosp Infect 1996;34:23-30.
Work of mental health review tribunals is increasing faster than detentions Editor—Wall et al provide a helpful outline of the significant increase in all psychiatric admissions and in those admitted under the Mental Health Act 1983.1 They mention, but do not document, the effect of these trends on mental health review tribunals. My study shows that the rate of appeals to, and hearings by, mental health review tribunals is increasing faster than increases in the episodes of detention that warrant a tribunal application. During 1991-3 the number of episodes of detention rose by 4245 (15% of 1991 total), the number of appeals to tribunals by 2032 (29%), and the number of hearings by 952 (26%). The episodes of detention include not only those admitted to hospital under the act but also those inpatients who were converted from another status to an episode of detention that presented the opportunity for an appeal or further appeal—for example, a conversion from informal to section 2 or 3, or from section 2 to section 3. Thus not only has the proportion of psychiatric inpatients
0.7
Detentions
0.6
Appeals
0.5 0.4 0.3 0.2 0.1 0
No rth Th am So es ut h An Th gl a m ia es an d Ox So fo ut rd h W es te rn No rth T an re nt d Yo rk W sh es i t M re id lan ds No rth W es t
Firstly, the right drug in the right dose (big) at the right time does save lives. Surprisingly to some, antibiotics do work and you need to get it right from the start. Secondly, there is not much point in saving your “best” antibiotic for the postmortem room. Next, we treat patients, not fevers, white cell counts, chest radiographs, or cultures. But on the other hand, just because the laboratory cannot grow something does not mean that there are no germs there causing trouble. And it does not mean that you should not consult them. You should. Finally, try to avoid poisoning the patient but always remember (and keep telling the managers) that saving lives costs money. There is nothing cheaper than a quick death.
Rate per 1000 population
Letters
Rates of detention under section 2 of Mental Health Act 1983 and appeals to mental health review tribunals per 1000 population of NHS regions, 1994-95
that are detained under the act risen but so has the proportion of those detained who appeal to and are heard by tribunals. I also observed considerable differences between NHS regions in the rate of detention per unit of population. The figure shows the rates of detention under section 2 and subsequent appeals. Detentions under section 3 showed a similar trend. Consequently, the burden of arranging and manning tribunals will vary between regions. G E Langley medical member, mental health review tribunals, south and west Hanningfields, Warborough Hill, Kenton, Exeter, Devon EX6 8LR
[email protected] 1 Wall S, Hotopf M, Wessely S, Churchill R. Trends in the use of the Mental Health Act 1984-96. BMJ 1999;318:1520-1. (5 June.)
Prophylaxis against early anaphylactic reactions to snake antivenom Stopping trials early may result in insufficient evidence being accrued Editor—Fan et al’s paper is the second in the BMJ recently to investigate prophylaxis against adverse effects of snake antivenom.1 Earlier, Premawardhena et al in Sri Lanka concluded that giving low dose subcutaneous adrenaline before antivenom could prevent acute adverse reactions.2 The Brazilian study (by Fan et al) showed no benefit in using promethazine as pretreatment.1 Perhaps more interesting than the conclusions, however, is that both these clinical trials were stopped early because of interim analyses; they provide examples of the use and pitfalls of such analyses. The Sri Lankan group stopped recruitment halfway through its study since the analysis showed a significant reduction in all acute adverse effects when adrenaline was used as pretreatment rather than placebo (P = 0.0002). Unfortunately, in subanalysis of the severity of adverse reactions in the two groups the differences in incidence of mild, moderate, and severe reactions barely reached significance due to the low power of the analysis (about 50%) and the small numBMJ VOLUME 319
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Letters bers. This is important since it is mainly the moderate and severe reactions that we wish to prevent. As it was, the trial was stopped because of a supposed benefit, but we cannot advise the use of subcutaneous adrenaline because of unconvincing evidence. In the Brazilian study the interim analysis was in the form of sequential analysis. The use of this method, and to some degree the negative outcome of the study, prevents arguments of the nature used above. Interim analyses are often required on ethical grounds, but final data analysis and clinical importance should be borne in mind when they are planned. Too often, emphasis is put on the ethics of continuing a trial in which some patients receive an apparently inferior treatment. Stopping the trial may, however, result in the evidence for the supposedly better treatment being insufficient for policy changes to be recommended—this too is unethical. Using and stating defined methodologies, as in Fan et al’s study, can help, but we must always bear in mind that statistics are an aid to reason, not a replacement for it. The dangers of stopping a trial too early have been addressed recently by Pocock and White3 and need to be fully appreciated by clinical researchers. Douglas E Ball drug information pharmacist, department of pharmacy Klara Tisocki lecturer, department of clinical pharmacology University of Zimbabwe, PO Box A178 Avondale, Harare, Zimbabwe
[email protected] 1 Fan HW, Marcopito LF, Cardoso JLC, França FOS, Malaque CMS, Ferrari RA, et al. Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites. BMJ 1999;318:1451-2. (29 May.) 2 Premawardhena AP, de Silva CE, Fonseka MMD, Gunatilake SB, de Silva HJ. Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial. BMJ 1999;318:1041-3. (17 April.) 3 Pocock S, White I. Trials stopped early: too good to be true? Lancet 1999;353:943-4.
Author’s reply Editor—Unfortunately, details on variables and the formula for the calculation of the limits of Wald’s graphic for the sequential analysis did not appear in the printed version of our paper, but they are available on the BMJ ’s website (www.bmj.com).1 Ball and Tisocki are invited to visit that site. On doing so, they may note that in Wald’s graphic there was an initial trend in preferences for placebo that did not prevail. The trial was stopped exactly when it was supposed to be stopped— that is, when one of the boundaries was reached. We share the authors’ concern about statistics, but in this study the proportion of reactions was virtually the same in both groups being compared (table 2 of the printed version of our paper). Hui Wen Fan doctor Hospital Vital Brazil, Instituto Butantan, 05503-900, Sao Paulo, Brazil
[email protected] 1 Parameters and formula for calculation of limits of Wald’s graphic. eBMJ 1999;318. www.bmj.com/cgi/content/full/ 318/7196/1451/DC1 (accessed 21 September 1999).
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Naturalistic treatment study of depression in general practice Clinical management is important in treatment of depression Editor—The striking finding of Malt et al’s study in patients with depression is not the superiority of combined pharmacotherapy and psychotherapy but the 47% complete response rate to placebo and psychological support, which was present from about 12 weeks onwards.1 Unfortunately, little information is given about the quantity and quality of the psychological support provided, although reference is made to the clinical management protocol used in the National Institute of Mental Health’s treatment of depression study, in which patients were seen regularly for 20-30 minute sessions of supportive therapy.2 3 In that study, at 16 weeks 42% of patients in the imipramineclinical management group had recovered compared with 21% in the placebo-clinical management group.3 The difference between the studies is unlikely to be due to severity of illness as in both studies the initial rating indicated illnesses of moderate severity (Malt et al’s study, mean initial Montgomery Åsberg depression rating scale = 26.7; National Institute of Mental Health study, mean initial Hamilton rating scale for depression = 19.5). However, the recovery criteria in Malt et al’s study were less stringent—namely, a 50% reduction in the score on the Montgomery Åsberg depression rating scale and improvement to at least only mild illness remaining. To compare the results usefully with those of other studies, data needed to be presented on the proportion of patients achieving full remission (a score < 6). The authors state that the findings challenge current guidelines that claim equality of effect between drug and psychological treatment in mild to moderate depression. These guidelines, however, have been based on controlled trials of formal psychotherapies rather than clinical management. In the National Institute of Mental Health study, cognitive therapy and interpersonal therapy were both superior to placebo-clinical management.3 What the findings do indirectly confirm is the crucial importance of good clinical management in enhancing the effectiveness of drug treatment. This has been shown in controlled trials showing the superiority of treatment based on guidelines compared with usual treatment of depression in primary care.4 5 Peter L Cornwall senior lecturer in community psychiatry University Department of Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
[email protected] 1 Malt UF, Robak OH, Madsu H-P, Bakke O, Loeb M. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)–I: randomised double blind study. BMJ 1999;318:1180-4. (1 May.) 2 Fawcett J, Epstein P, Fiester SJ, Elkin I, Autry JH. Clinical management imipramine/placebo administration manual. Psychopharmacol Bull 1987;23:309-21. 3 Elkin I, Shea T, Watkins JT, Imber SD, Sotsky SM, Collins JF, et al. National Institute of Mental Health treatment of
depression collaborative research program. Arch Gen Psychiatry 1989;46:971-82. 4 Katon W, Von Korff M, Lin E, Simon G, Walker E, Bush T, et al. Collaborative management to achieve treatment guidelines. JAMA 1995;273:1026-32. 5 Schulberg HC, Block MR, Madonia MJ, Scott CP, Rodriguez E, Imber SD, et al. Treating major depression in primary care practice. Eight month clinical outcomes. Arch Gen Psychiatry 1996;53:913-9.
Antidepressants are overrated Editor—The most interesting aspect of the results of the trial by Malt et al is that the difference between antidepressants and placebo was not impressive and was of doubtful clinical relevance.1 At most it consisted of a difference of 3 points on a scale with a maximum of 60 points and a pretreatment average value of 27. In most subjects whose depression was classified as severe or major depression the difference was smaller and not significant. At least part of this difference probably represents the non-specific effects of taking an active drug as opposed to an inert placebo. It has been found that both researchers and patients can distinguish antidepressants, including selective serotonin reuptake inhibitors, from inert placebos.2 3 This “unblinding” effect may be important, since trials comparing antidepressants with active placebos have generally found smaller effects.4 Side effects are obviously an important way in which the identity of a drug or placebo is revealed. Unfortunately— especially since the doses of drugs used were higher than those used routinely—Malt et al provide no information on this outcome except to say that side effects were “few and rather insignificant.” But patients may be able to identify that they are taking an active drug without necessarily reporting side effects. The authors did not investigate whether patients could identify which group they were in, but they do report that none of the general practitioners could identify the patient-drug combination correctly. It is not clear, however, that this was assessed systematically, since by chance some of the general practitioners would be expected to guess correctly. These reservations about the importance of Malt et al’s findings are consistent with a recent meta-analysis which found that differences between antidepressants and placebo were less noticeable than has traditionally been assumed.5 Doctors must be cautious about recommending routine drug treatment for mild and moderate depression in general practice on ethical as well as scientific grounds. It is clearly in the interests of the pharmaceutical industry to promote the notion that drug treatment can resolve human unhappiness and the problems of living. Professionals have a duty to consider the wider implications of such a scenario. Joanna Moncrieff specialist registrar in psychiatry Department of Psychological Medicine, Chelsea and Westminster Hospital, London SW10 9NG
[email protected] 1 Malt U, Robak HO, Madsbu H-P, Bakke O, Loeb M. The Norwegian naturalistic treatment study of depression in
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general practice (NORDEP)—1: randomised double blind study. BMJ 1999;318:1180-4. (1 May.) White K, Kando J, Park T, Waternaux C, Brown WA. Side effects and the “blindability” of clinical drug trials. Am J Psychiatry 1992;149:1730-61. Kranzler HR, Burleson JA, Korner P, del Boca FK, Bohn MJ, Brown J, et al. Placebo controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am J Psychiatry 1995;152:391-7. Moncrieff JM, Wessely S, Hardy R. Meta-analysis of trials comparing antidepressants with active placebos. Br J Psychiatry 1998;172:227-31. Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C. Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry 1999;174:297-303.
Author’s reply Editor—Cornwall asks for the proportion of patients achieving what he calls full remission (score on the Montgomery Åsberg depression rating scale < 7) in our study to compare it with Elkin et al’s study. After 16 weeks 38/87 (44%) taking sertraline (odds ratio 0.45; 95% confidence interval 0.23 to 0.89) and 31/84 (37%) taking mianserin (0.60; 0.30 to 1.20) had a total score of < 7 compared with 23/89 (26%) taking placebo. Our results are comparable to those of Elkin et al’s study.1 Nevertheless, we think that emphasising just a score of < 7 at a given time addresses only part of the picture. Because of the serious consequences of depression, differences in the proportion of subjects having final scores in the range of 7-11 with a given treatment are also clinically important. The difference in clinical disability between patients with a score of, say, 8 or 18 may be that of being able to work or not. Moncrieff suggests that the additional benefit of drugs in our study is due to non-specific effects of active treatment. This argument has less validity in primary care. The studies cited by Moncrieff et al are conducted with depressed outpatients, not primary care attenders.2 In our experience, primary care attenders have strikingly fewer side effects than do psychiatric outpatients, whatever the drug given. In our study the general practitioners were required to explore possible side effects systematically. This method provides a higher prevalence of side effects than just recording spontaneously reported side effects. The mean number of baseline-corrected side effects during the study was 7.11, 6.51, and 6.45 after 8 weeks of treatment with sertraline, mianserin, or placebo respectively, and 3.16, 3.09, and 3.02 after 24 weeks of treatment. Unipolar and bipolar depressions are the leading causes of the world’s total disability adjusted life years. When several features of this study (statistical power 0.95, 70% completing 16 weeks of treatment, no exclusion of patients who responded to placebo, measurement of serum drug concentrations to control for compliance, reliable raters, psychological support as it is provided in general practice) are considered, the superiority of combined drugpsychological treatment of depression in primary care is remarkable. If this treatment was adopted worldwide a considerable reduction in disability adjusted life years should be achieved. 922
We agree, however, that good clinical management is the key to therapeutic success. The high response rate to good clinical management and placebo is remarkable indeed. More research on identifying predictors of response to different treatments is obviously needed. Ulrik Fredrik Malt professor of psychiatry Department of Psychosomatic and Behavioural Medicine, University of Oslo, N-0027 Oslo, Norway
[email protected] 1 Elkin I, Shea T, Watkins JT, Imber SD, Sotsky SM, Collings JF, et al. National Institute of Mental Health treatment of depression collaborative resarch program. Arch Gen Psychiatry 1989;46:971-82. 2 Moncrieff JM, Wessely S, Hardy R. Meta-analysis of trials comparing antidepressants with active placebos. Br J Psychiatry 1998;172:227-31.
UK’s diagnostic criteria for diabetes are different from US’s Editor—In the article on glycaemic control in diabetes the American author states that diabetes is characterised by a fasting plasma glucose concentration of >7.0 mmol/l or a plasma glucose concentration of >11.1 mmol/l two hours after a 75 g oral glucose load.1 Understandably, he has described the American guidelines for diagnosing diabetes,2 but these are not the same as those in the United Kingdom. Here, the World Health Organisation’s criteria are still used; these define the fasting plasma glucose cut off point as >7.8 mmol/ l.3 The WHO may possibly adopt the American guidelines in the future,4 but in the meantime we have to be wary of giving clinicians conflicting advice which may lead to diagnostic difficulties with their patients.5 Eric S Kilpatrick consultant in chemical pathology Hull Royal Infirmary, Hull HU3 2KZ
[email protected] 1 Herman WH. Clinical evidence: Glycaemic control in diabetes. BMJ 1999;319:104-6. (10 July.) 2 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183-97. 3 World Health Organisation. Diabetes mellitus: report of a WHO study group. WHO Tech Rep 1985;727. 4 WHO Consultation Group. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus; provisional report of a WHO consultation. Diabetic Med 1998;15:539-553. 5 DECODE Study Group. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. BMJ 1998;317:371-5.
Money to modernise adult mental health services is insufficient Editor—The government has great ambitions for adult mental health services and has raised the public’s expectations that community care will be reformed. Unfortunately, the new funding available to most health authorities for that purpose does not match the rhetoric or compensate for the disinvestment in mental health services that occurred as the large psychiatric hospitals were closed.1
With the publication of the new mental health strategy the secretary of state announced £700m of new money for mental health services from the modernisation fund. It was stated that “the new investment will provide extra beds of all kinds, better outreach services, better access to new anti-psychotic drugs, 24 hour crisis teams, more and better trained staff, regional commissioning teams for secure services, and development teams.”2 This created the impression that services for adults of working age would be the principal beneficiaries of the new funding and that allocations would be sufficient to allow a major overhaul of local services. The true picture is somewhat different. The £700m is to be allocated over three years. Altogether £46m of the first year’s allocation of £146m is for local authorities. Only £40m of the health authority allocation is for adult mental health services, and just £19m has actually been distributed to health authorities for one or more of three specific purposes: to provide 24 hour staffed beds, to develop assertive outreach teams, and to fund the prescription of more new “atypical” antipsychotic drugs. The remaining £21m is to establish new secure beds (£14m), to support a development fund to implement the national service framework (£5m), and for a “beacon service challenge fund” (£2m). Decisions about the distribution of the £19m were based on three factors: service gaps identified during the autumn review, a judgment of need in each health authority, and evidence of greater need in London. The net result is that only two of the 100 health authorities received more than £1m additional money for new developments in adult mental health for 1999-2000; 71 received less than £100 000 and 53 received less than £50 000. These are paltry sums when set against some of the incidental costs of modern mental health care borne by health authorities. A single placement in a private secure hospital would cost about £100 000 a year; to provide a single acute psychiatric bed costs £50 000-70 000 a year; and an independent homicide inquiry would cost £0.5m-1.5m. The first year’s allocation of the modernisation fund also coincides with a larger than average staff pay award (only partially funded by the government) and the requirement for trusts to make the usual cost efficiency savings. Paul Lelliott director Royal College of Psychiatrists’ Research Unit, London SW1X 7EE 1 Lelliott P, Sims A, Wing J. Who pays for community care? The same old question. BMJ 1993;307:991-4. 2 Department of Health. Modernising mental health services: safe, sound and supportive. London: Department of Health, 1998.
BMJ VOLUME 319
2 OCTOBER 1999
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