Medical prescribing adviser. Hilton Hospital, .... the perspective of their analysis is society, indirect .... Charing Cross and Westminster Medical School,. London ...
With regard to the choice of antidepressant, as Freemantle and colleagues point out, general practitioners may, rightly or wrongly, argue the case for their particular patient against population evidence of cost-benefit. Such arguments will be difficult to sustain if the simultaneous prescription of agents as toxic as tricycic antidepressants but with much more doubtful benefits is maintained. Perhaps we are in danger of underestimating the extent to which commercial interest determines our priorities for "rational prescribing" and influences trends in prescribing.5 D TRACEY Medical prescribing adviser
Hilton Hospital, Invemess IV2 3PH 1 Freemantle N, House A, Song F, Mason JM, Sheldon TA. Prescribing selective serotonin reuptake inhibitors as a strategy for prevention of suicide. BMJ 1994;309:249-53. (23
July.) 2 Cassidy S, Henry J. Fatal toxicity of antidepressant drugs in overdose. BMJ 1987;295:1021-4. 3 Registrar General for Scotland. Annual report. Edinburgh: General Registry Office, 1992. 4 MeReC. Combination analgesics. MeReC Bulletin. 1993;4:45-7. 5 Avorn J, Chen M, Hartley R Scientific versus commercial sources of influence on the prescribing behavior of physicians. AmyrMed 1982;73:4-8.
Conflicting reports confuse prescribers EDrrOR,-N Freemantle and colleagues conclude that the cost per life year gained through avoiding suicides by routine first line use of selective serotonin reuptake inhibitors is likely to be high.' They recommend that the shift to considerably more expensive options must be investigated further. This adds to the confusion over the indications for prescribing selective serotonin reuptake inhibitors. Mackay predicted that the tricyclic antidepressants and related drugs might be heading for retirement.2 In a review selective serotonin reuptake inhibitors were not recommended as first line treatment for depression; it was concluded that they were no more effective than tricyclic antidepressants in patients with moderate to severe depression and were much more expensive.3 Expenditure on antidepressants rose by half in 1992,4 and a major factor in this was the introduction of selective serotonin reuptake inhibitors. Yet recently Bebbington concluded that the overall cost of successful treatment with selective serotonin reuptake inhibitors could be less than that with the older, cheaper drugs. With the introduction of the NHS reforms, financial aspects of drug treatment are receiving
increasing attention. This has brought into focus cost-benefit and risk-benefit analysis of antidepressants. Several questions on the prescribing of selective serotonin reuptake inhibitors remain
unanswered-for example, whether they should be prescribed as first line antidepresssants and whether they are more cost effective in the long term. Perhaps Bebbington's argument that previous publications took no account of the economic benefits in the long term of prescribing selective serotonin reuptake inhibitors may partly answer the second question. It is suprising that no consensus exists on using selective serotonin reuptake inhibitors in depression, which is so common and disabling. We agree with Freemantle and colleagues that further research is required. Perhaps the Royal College of Psychiatrists could take a leading role in coordin-
ating such research. RABIN GONZAGA Senior house officer PRAKASH NAIK
2 Mackay AVP. A review of the selective serotonin reuptake inhibitors. St Asaph, Clwyd: Unicom Health Communications Services, 1993: 1-4. 3 Selective serotonin reuptake inhibitors for depression? Drug Ther Bull 1993;31:57-8. 4 Prescribing costs. Drug Ther Bull 1993;31:87. 5 Bebbington P. Are new antidepressants really more expensive? Prescriber 1994;5:61-2.
Authors' assumptions are misleading EDITOR,-AS the methodology of economic analyses differs from that of clinical trials, most doctors are still unfamiliar with it. Authors of such analyses therefore have a particular responsibility to choose the appropriate figures, numbers, and assumptions. Drummond et al have published a checklist of 10 critical questions and items that an economic comparison of different treatments should contain.' Using this checklist, we analysed N Freemantle and colleagues' paper comparing selective serotonin reuptake inhibitors with tricyclic antidepressants.' We found some major deviations on several items (1, 2, 4, 5, 6) in the checklist. The question may have been well defined, but it refers to only one aspect of switching treatment from tricyclic antidepressants to selective serotonin reuptake inhibitors, so we have great doubts about the validity of the authors' answer to this subitem. The authors claim that they did not find any other relevant difference between the two classes of drugs; they refer to a meta-analysis that they performed.3 Many points in that analysis were criticised, and Montgomery et al's results differed greatly from theirs.4 We are surprised that the authors do not mention this controversy. We believe that the non-drug treatment that is an important alternative to reduce the suicide rate in Britain should have been included in the analysis. The authors included only the costs of the drugs in their analysis. Their claim that there is no other difference is doubtful, as mentioned above. The direct costs of non-fatal attempts at suicide have been omitted. It is not enough to mention the difficulty of finding appropriate figures to estimate these costs when a considerable differernce between the interventions must be expected. King and Sorenson were able to find such figures for an article about the costs of depression in Britain.' The authors have also omitted the indirect costs of suicide and attempts at suicide; as they claim that the perspective of their analysis is society, indirect costs must be included. The reference to the secrecy of some data used makes it difficult for critical readers to follow their assumptions. Taking all these points into account, we believe that this evaluation was poorly performed. The authors' assumptions are misleading and must be interpreted with great caution. ARNO BRANDT Managing director RITO BERGEMANN Medical director Institute for Medical Informatics and Biostatistics, CH-4125 Riehen, Switzerland
B K PURI
1 Drummond MF, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press, 1992:35-8. 2 Freemantle N, House A, Song F, Manson J, Sheldon TA. Prescribing selective serotonin reuptake inhibitors as strategy for prevention of suicide. BAU 1994;309:249-53. (23 July.) 3 Song F, Freemantle N, Sheldon TA, House A, Watson P, Long A, et al. Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability. BMJ 1993;306:683-7. 4 Montgomery SA, Henry J, McDonald G, Dinan T, Lader M, Hindmarch I, et al. Selective serotonin re-uptake inhibitors: meta-analysis of discontinuation rates. Int Clin Psycho-
pharmacol 1994;9:47-53. 5 King P, Sorenson J. The costs of depression. Int Clin Psycho-
pharnacol 1993;7:191-5.
Consultant psychiatrist Lyndon Clinic (Resource Centre), Solihull B92 8PW 1 Freemandle N, House A, Song F, Mason JM, Sheldon TA. Prescribing selective serotonin reuptake inhibitors as a strategy
for prevention of suicide. BM7 1994;309:249-53. (23 July.)
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suicide owing to their high costs relative to the costs of other antidepressants.' The premise is incorrect. Mianserin and maprotiline have tetracyclic structures, while trazodone has a chemical configuration completely unrelated to that of tricyclic antidepressants. Furthermore, the authors fail to mention whether the absolute figures for deaths related to antidepressants, taken alone or in combination with other psychotropic agents, include those caused by overdoses of atypical antidepressants such as phenelzine and tranylcypromine. A prerequisite of scientific papers is that the methods of a study should be described in sufficient detail to allow others to replicate it. This is clearly impossible with this paper as some of the most important references are to personal communications and no formulas are provided for the critical calculations. With regard to the cost of selective serotonin reuptake inhibitors, the authors have not reduced the prices as they indicate in their methods section. While the reduced price for fluoxetine is correct, a revised estimate of the costs of the others, at three quarters of their current value, would be sertraline £29.83, fluvoxamine £26.25, and paroxetine £23.75. These prices are substantially lower than those indicated in table II, and from these estimations the extrapolated figures in tables III and IV seem to be incorrect. While the authors suggest that the use of selective serotonin reuptake inhibitors in preference to tricyclic antidepressants leads to too great a financial burden, they have failed to incorporate in their calculations the savings that arise from the reduction in non-fatal suicide attempts. Indeed, many people who take an overdose of selective serotonin reuptake inhibitor do not require admission to hospital overnight. The authors suggest that the newer less expensive antidepressants such as maprotiline, mianserin, and viloxazine, if more widely used, would result in a more cost effective reduction in the suicide rate. They have failed to take into account the fact that the profile of side effects and the potential drug interactions of these antidepressants would limit their clinical substitution for selective serotonin reuptake inhibitors. The authors make the point that selective serotonin reuptake inhibitors confer little additional clinical benefit in comparison with tricyclic antidepressants and largely base this on the results of a meta-analysis by the same group.2 That study has been disputed.'4 Indeed, a more recent metaanalysis suggested "that there is a significant and clinically important advantage for the [selective serotonin reuptake inhibitors] compared with the [tricyclic antidepressants] in the acceptability of treatment as measured by the number of discontinuations due to side-effects reported in published studies."4 Finally, the authors state that selective serotonin reuptake inhibitors are "often" used in conjunction with sedatives, quoting their previous paper as a reference; they failed, however, to mention this fact and supporting references in their previous article.
Methodology is inadequately described ED1TOR,-N Freemantle and colleagues question the prudence of prescribing selective serotonin reuptake inhibitors as a means of preventing
Honorary lecturer
Department of Psychiatry, Charing Cross and Westminster Medical School, London W6 8RP J H THAKORE
Lecturer
Department of Psychological Medicine, Medical College of St Bartholomew's Hospital, London EC1A 7BE 1 Freemantle N, House A, Song F, Mason JM, Sheldon TA. Prescribing selective serotonin reuptake inhibitors as strategy for prevention of suicide. BMJ 1994;309:249-53. 2 Song F, Freemantle N, Sheldon T, House A, Watson P, Long A, et al. Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability. BMJ 1993;306:683-7. 3 Robertson MM, Katona CL.E. Effective and acceptable treatment for depression. EMY 1 993;306:l 125-6. 4 Montgomery SA, Henry J, McDonald G, Dinan T, Lader M, Hindmarch I, er al. Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates. Int Clin Psychopharmacol 1994;9:47-53.
BMJ VOLUME 309
22 OCTOBER 1994
