Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Another plausible alternative explanation
- Dan E Bilsker (10 May 2003)
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Conflicts of interest
- Gurli Bagnall (10 May 2003)
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It will be more interesting to include patients who recieve ECT..etc?
- AK Al-Sheikhli (13 May 2003)
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Antidepressants do not reduce suicide rates
- Peter H Ankarberg (13 May 2003)
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Decline in older age suicide rate pre-dates 1991
- Thomas J Verberne (14 May 2003)
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More than antidepressants are needed to avert suicide
- Diego De Leo, Ester Cerin (15 May 2003)
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A Patient's View
- Simon D Allen (16 May 2003)
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Caution in interpretation
- Stephen J Senn (19 May 2003)
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Misleading analysis
- Joanna Moncrieff (19 May 2003)
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Decline in older suicides in Australia was much greater before the SSRIs were introduced
- Brian M Draper (21 May 2003)
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Misleading assessment of the relation between trends in antidepressant prescribing and suicide.
- David Gunnell, Nicos Middleton, Jonathan AC Sterne (6 June 2003)
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Responses to our critics
- Wayne D. hall, Wayne Hall, Andrea Mant, Phillip Mitchell, Valerie Rendle, Ian Hickie and Peter McManus (10 June 2003)
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Re: Responses to our critics
- Thomas J P Verberne (16 June 2003)
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Dan E Bilsker, Consulting Psychologist MHECCU, University of British Coumbia, 605-1125 Howe Street, Vancouver, BC, Canada V6Z 2K8
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This data is interpreted as showing that increased antidepressant prescribing and associated care has resulted in lower rates of suicide, presumably due to reduced depression symptomatology, based on the observation that older age groups who have received the greatest increase in antidepressant prescription also show the greatest decrease in suicide. However, there is an alternative explanation that should be ruled out. It is noted by the authors that the increase in antidepressant prescribing has involved a shift from older antidepressants to SSRIs and that SSRIs have “greater safety in overdose than older types of antidepressant”. The differential decrease in suicide mortality by age group could reflect a proportionately greater reliance upon antidepressant overdose as a suicide method in older age groups. If the proportion of individuals using antidepressant overdose as a suicide method increases with age, and if individuals in these older groups are unlikely to substitute other methods, one would expect that improved safety of antidepressant medication would have its greatest impact upon suicide rates in older age groups. There may have been no decrease in actual rate/severity of depression related to increased treatment nor a decrease in rate of suicide attempts, but only a decrease in lethality of these attempts. There is some research evidence relevant to this alternative explanation. One study analyzed data from the Oxford Monitoring System for Attempted Suicide between 1985 and 1997 and found that older people were more likely to use antidepressant overdose as a suicide method.(1) Differential age-group impact has been found for suicide by self- asphyxiation by car exhaust after the introduction of catalytic converters rendered this method less lethal: there was an overall decrease in suicide except for young people, who substituted other methods. (2) Based on this alternative explanation, the substantially increased rate of antidepressant prescription may be a red herring, having no significant relationship to the decreased rate of suicide in older age groups. This would not take away from the importance of having introduced less-toxic methods of depression treatment, clearly a major step forward in psychiatric practice. 1. Townsend E, Hawton K, Harriss L, et al. Substances used in deliberate self-poisoning 1985-1997: trends and associations with age, gender, repetition and suicide intent. Social Psychiatry and Psychiatric Epidemiology 2001; 36: 228-234. 2. Amos T, Appleby L, Kiernan K. Changes in rates of suicide by car exhaust asphyxiation in England and Wales. Psychological Medicine 2001; 31: 935-939. Competing interests: None declared |
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Gurli Bagnall, Patients' Rights Campaigner Independent
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The SSRIs have had a very bad press for a number of years. The emphasis during this past year has been upon their addictive qualities (1) and the fact that some users become suicidal only AFTER taking these drugs. It came then as a surprise to find a glowing paper about SSRIs in the latest BMJ. The authors have close associations with the drug industry, yet the BMJ saw fit to publish this advertising material. At the same time, it chose to ignore the very newsworthy fact that benzodiazepines are now “to be ranked alongside morphine in the list of ‘danger drugs’” (2). It took more than 40 years of public concern about the BZDs to reach this point, and during that time, we saw the same unethical advertising material published under the guise of papers or articles. Will it take another 40 years for the dangers of the SSRIs to be acknowledged by the medical profession? The BMJ is influentital and its support of such practices is disappointing to say the least. References: 1. BBC News 11 June, 2001 2. The Independent, April 20, 2003 Competing interests: None declared |
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AK Al-Sheikhli, Locum Consultant Psychiatrist Medical Centre,2Manor Court Avenue,Nuneaton CV11 5HX,England.
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Dear Editor, It was interesting to read the paper of Hall et al, Association between antidepressants prescribing and suicide in Australia,1991-2000, Trend analysis..(BMJ,2003). I think including patients who recieve other sorts of treatments for depressive illness, for e.g, psychological methods of treatment and electroconvulsive therapy, might give different results? With my best regards, A.K.Al-Sheikhli,MRCPsych DPM Competing interests: None declared |
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Peter H Ankarberg, clinical psychologist, licensed psychotherapist Samtalscentrum Unga Vuxna, Repslagargatan 5A, 611 30 Nyköping, Sweden
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Rapid response to Hall et als article in BMJ 10 May 2003: “Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis” Peter Ankarberg, clinical psychologist, licensed psychotherapist In their article in BMJ 10 May 2003: “Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis” Hall et al came to the conclusion that the increase in antidepressant use in Australia have contributed to the declining suicide rates. This conclusion is not supported by their own data or by recent meta-analyses of controlled clinical trials for antidepressants. In Hall et als article it is shown that the biggest increase in antidepressant use 1990-2000 has been in the ages 15-44. At the same time the rate of suicide for this age span has increased in Australia. For men aged 25-34 the use of antidepressants has increased more than six times during the period. At the same time the suicide rate has increased with almost 17 percent. Using this correlation in time in the same way that Hall et al use the total correlation for all ages one could argue that antidepressants increase the risk of suicide for people younger than 45 and particularly for males 25-34 years. Neither this conclusion nor Hall et als are of course scientifically valid. To make valid conclusions we need controlled studies. Hall et al state that there is little direct evidence that antidepressants reduce the suicide rate because even large clinical trial have limited power to detect a reduction. They fail to mention that since the year 2000 three large meta-analyses on antidepressants and suicide have been published. Together they include over 60 000 depressed patients in randomised clinical trials comparing antidepressants to placebo. The majority of trials were short term but several long term trials were included with a total of 1949 patients. The results of all meta-analyses, both for short and long term treatment, were that suicide was slightly more common among patients taking antidepressants compared to patients taking placebo. To summarise: Hall et als material does not show that antidepressants reduce the rate of suicide. At the same time placebo controlled randomised clinical trials show that the rate of suicide is higher with antidepressants than it is with placebo. From this it seems clear that the only reasonable conclusion is that antidepressants do not reduce the rate of suicide. There might however be a slight increase in suicide rates for patients treated with antidepressants although further studies are needed to make any firm conclusions. 1 Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. British Medical Journal 2003; 326 2 Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: Analysis of FDA reports. Am J Psychiatry 2003; 160: 790-92. 3 Khan A, Warner HA, Brown WA: Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: An analysis of the Food and Drug Administration database. Arch Gen Psychiatry 2000; 57: 311-317. 4 Storosum JG, van Zwieten BJ, van den Brink W, Gersons B, Broekmans AW. Suicide risk in placebo-controlled studies of major depression. Am J Psychiatry 2001; 158: 1271-75. Competing interests: None declared |
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Thomas J Verberne, none 14 Crampton Crescent, Rosanna, Vic., 3084, Australia
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Hall et al. (1) state: ". . . the association we observed between antidepressant prescribing and suicide may reflect increased recognition, diagnosis, and treatment of depression by general practitioners as much as any pharmacological effects of antidepressant medication." The time scale they took into account was the decade 1991-2000. If they are right in their conjecture, the processes involved must have started some sixty or seventy years ago, if not in Australia then in the United States. In the U.S., a steady decline in the suicide rate of people aged 65 and over has been well-documented: from 45.3, in 1933, to 21.5, in 1986. (1) Murphy & Wetzel (2) showed the same decline for the period 1940- 1975. The following table, presenting age-specific white male suicide rates in five-year intervals, has been extracted from their Table 6.
1940 1975
65-69 57.5 35.0
70-74 59.3 37.6
75-79 65.8 44.9
80-84 66.4 44.6
The decline of the suicide rates in older age groups started well before the introduction of the tricyclics, that is, before there was any effective pharmaceutical treatment of depression. 1. Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between anti-depressant prescribing and suicide in Australia, 1991-2000: trend analysis BMJ 2003; 326: 1008-1011 2. McIntosh JL. In: Life Span Perspectives of Suicide, A. A. Leenaars, editor, Plenum Press 1991:60-61. 3. Murphy GE, Wetzel RD. Suicide risk by birth cohort in the US, 1949- 1974. Arch Gen Psychiatry 1980; 37: 519-523. Thomas J P Verberne
Competing interests: None declared |
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Diego De Leo, Professor of Psychopathology Australian Institute for Suicide Research and Prevention, Griffith University, Ester Cerin
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The conclusions presented in Hall et al.’s (2003) paper on the association between antidepressants prescribing and suicide are questionable. The authors claim that their findings support the contention that there is a clear association and, perhaps, causal relationship between antidepressant prescribing and suicide, especially in older males and females. Unfortunately, the authors fail to duly acknowledge that their data also indicate a lack of impact of antidepressants on suicide in younger individuals, which, indeed, might have been used to corroborate an opposite standpoint to that presented in the paper. For instance, tables 1 and 2 show that, despite an increase in antidepressant use, both male and female subjects aged 15 to 44 reported an increase in suicide rates. Additionally, the relative increase in antidepressant use in this age segment of the population was much higher (e.g., OR = 11.9 in 15-24 year old males) than that observed in the elderly (e.g., OR = 1.97 in 65-74 year old males). These results question the existence of an unequivocal association between antidepressant prescriptions and suicide rates. Of course, it could be argued that without antidepressants the rates of suicide in the younger segment of the population could have been even higher. However, the research design adopted in the present study cannot provide a reliable answer to these questions. It should be also noted that if we calculate the correlation between absolute changes in antidepressant use and suicide rates in the age groups, controlling for the differences in initial levels (1986-1990) of antidepressant use and suicide rates, the strength of association between the two variables appears to be much lower and in the opposite direction than that reported by Hall et al. (eg., r = 0.04 for males and r = 0.33 for females; p< 05). Furthermore, the fact that the authors found a higher correlation between age groups and changes in suicide rates than between estimated changes in antidepressant prescriptions and suicide rates implies that some age-related factors may be responsible for the observed association. We believe that these findings should have raised at least some concerns about the spuriousness of the observed antidepressant- suicide relationship. It should be also noted that Hall at al.’s paper presents an overly biased overview of the current findings on the relationship between antidepressants and suicidal behaviour. Pharmacoepidemiological investigations, pooled analyses, and randomised control trials have yielded conflicting evidence in this respect and it is not clear whether antidepressants may prevent or even provoke suicidal behaviours (Baldwin, 2000). Another problem associated with the conclusions reached in Hall et al.’s study regards the authors’ claim that in the examined timeframe there was “no evidence of marked changes in method of suicide”. This is incorrect. There was indeed a substantial decline in suicide by drugs overdosing. This phenomenon was observed in all age groups, but was more pronounced in older adults, reaching a 40% decrease in the over 75 and affecting proportionately more women than men, who are notoriously more prone to attempting suicide with prescribed medications (ABS, 2001). As suggested by another commentator of Hall et al.’s paper (D. Blisker), the possible impact of newer, safer antidepressants on suicide rates in elderly could be explained by a reduction in access to lethal means of suicide. Not to mention that suicide rates, especially in older women in Australia, have demonstrated a nearly constant decline since the pre- antidepressants era. This happened in most, if not all, Anglo-Saxon countries, suggesting the (powerful) influence of socio-cultural factors (De Leo, 2001). Finally, it is important to acknowledge that suicide is not simply a function of depression but requires integrated efforts at all levels of the community, all round. In fact, a recent study (Bertolote et al., in press) showed that by treating with a 70% efficacy index ALL depressed people, the obtainable reduction in suicide rates would not be higher than 12%. Consequently, although depression is one of the factors associated with higher suicide risk, concentrating most efforts only in this direction would be dangerously reductionistic and unjustifiable (De Leo, 2002). References: 1. Australian Bureau of Statistics (2001). Suicide, Australia. Information paper, Canberra, Australian Bureau of Statistics 2. Baldwin, D.S. Pharmacological provocation and prevention of suicidal behaviour. Intern Rev Psychiatry 12: 54-61. 3. Bertolote, J.M., Fleishman, A., De Leo, D., et al. Mental disorders and suicide (editorial). Br J Psychiatry (in press). 4. Blisker, D.E. Another plausible alternative explanation. Rapid responses to: Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. BJM 2003, May 10. 5. De Leo, D. (2001). Suicide and Euthanasia in Older Adults. A Trans- cultural Journey. Hogrefe/Huber, Goettingen. 6. De Leo, D. (2002). Why are we not getting any closer to preventing suicide? (editorial). Br J Psychiatry 181: 372-374. Competing interests: None declared |
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Simon D Allen, Patient n/a
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As a person with severe Bipolar Mood disorder, who has been, but is no longer, on several different antidepressants, I feel that I can add something - personal experience. 1. Antidepressants work. I was transformed from a wreck who was physically shattered, suicidal and terrified of everything, especially other people. After taking anti-depressants I began to improve. It is simply not credible that such an improvement, which I have seen replicated in many other patients, is caused by a friendly chat with a doctor, or the placebo effect. I was terrified of the doctor, and had no hope that the pills would help me; no hope of any kind. 2. Reducing suicide is not the only goal of antidepressants. If suicides remained constant, but patient's quality of life improved whilst they were alive then the drugs would be worthwhile. Being depressed is hell; there is nothing worse. People who have not been suicidally depressed cannot imagine what it is like. Unfortunately this fact colours much discussion and study in the medical community. 3. I believe that one reason SSRIs increase suicide risk may be that, when you are in the depths you wants life to end, but don't have the energy or will to act on the desire. As one starts to recover, the physical and mental torpor lift faster that the despair. There is then a dangerous crossover period when you still have feelings of darkness, hopelessness and fear, but you are full of energy. This is when there is a real danger of self destructive behaviour. It is very important that patients are monitored over this period, but the depressive thoughts may also breakthrough later. Being suicidal once makes it easier to contemplate later - the taboo has been nroken and it now seems a viable option, always there. 4. In my personal experience, GPs do not have the skills necessary to be dispensing antidepressants. They prescribe them to patients who present with depression, without finding out if the depression is a manifestation of something else. In my instance, I was twice pescribed SSRIs with no other mood stabilisers as GPs failed to diagnose my Bipolar Disorder. The second time I had a severe reaction. I am sure that order conditions are missed by busy GPs who see a depressed individual and automatically prescribe an SSRI from whichever company last gave him or her a freebie. Competing interests: None declared |
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Stephen J Senn, Professor of Pharmaceutical and Health Statistics University College London, London, WC1E 6BT
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One should be cautious about using correlated time series to judge cause and effect. At the very least it seems prudent to adjust figures for any possible overall secular trend. There are also very many alternative models that could have been envisaged by Hall et al1. I tried a number of different approaches, two of which I report here. For both of these I used data on numbers of suicides for 1991-1992, 1994-1996 and 1998-2001 for males and females and by ten-year age group starting at age 15 and finishing at age 75, as my response variable. (These values were obtained from the Australian Bureau of Statistics2.) Main effects of age and sex as categorical variables and their interactions as well as year as a main effect, also treated as a categorical variable, were fitted as standardising predictors. Poisson regression (with re-scaling by residual deviance) and negative binomial regression, with total (log) years of exposure as an offset in both cases, were used as fitting approaches and use of antidepressant (defined daily dose/100 people/day) as given in Table 2 of Hall et al was used as a predictor. A negative association with antidepressant use and suicide was observed, as was in the paper by Hall et al. However, for the first approach this was not significant, estimate (est) =-0.0010, standard error (SE) =0.0009, p=0.27, and for the second it was just significant, est=-0.0014, SE=0.0006, p=0.02. No doubt many other approaches could have been envisaged. It seems to me, however, that the relationship is not so strong as to be robust to changes in modelling approaches. As such, it is less than compelling and, in any case, very many difficulties of interpretation remain, to some of which the Hall et al referred1. In short, I think one should be sceptical about claiming a benefit of increased anti-depressant use in terms of reduced risk of suicide on the basis of such data. It may be mere coincidence but is certainly worth studying in other societies. References 1. Hall DW, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. Br. Med. J. 2003;326:1008-1012. 2. Australian Bureau of Statistics. Information Paper: Suicides 2001, 2002. Competing interests: The author is a consultant to the pharmaceutical. This note was prepared completely independently of any other party. |
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Joanna Moncrieff, Senior Lecturer, University College London Department of Psychiatry and Behavioural Sciences, UCL, 48, Riding House Street, London, W1N 8AA,
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Dear Editor, As already noted Hall et al’s (1) data on suicide rates and antidepressant prescribing contradict their own conclusions. The conventional and intuitive way of analysing trends in levels of antidepressant use by age group would be to look at ratios of levels of use in 1998-2001 compared with 1990-1991. Using the data on bmj.com, this shows that levels of use increased 7.5 times for men aged 25-34 and 2.1 times for men aged 75-84, for example. Spearman correlations were conducted using these ratios for all age groups and the difference in suicide rates as defined by the authors. This revealed a strong positive correlation. Increases in suicide rates were associated with higher rates of increase of antidepressant use. For men, Spearman’s Rho was 0.86, p=0.007. For women, it was 0.76, p=0.03. The authors appear to have reached their figures by analysing absolute differences in levels of prescribing. The use of Daily Dependent Dose (DDD) is also problematic and not clearly explained. DDDs represent units of World Health Organisation defined therapeutic doses. Thus the increase in antidepressant use in older age groups is probably accounted for partly by a change from lower dose tricyclic antidepressant prescribing to prescribing selective serotonin reuptake inhibitors at standard doses. However, evidence that lower doses of tricyclics are less efficacious than standard doses is not strong (2). In addition, DDDs relate to the general adult population. They will therefore underestimate prescribing levels of tricyclic antidepressants in the elderly where it is accepted that therapeutic and tolerable doses will be lower. It remains very difficult to prove that the massive increase in antidepressant prescribing has had any objective and positive impact on the health of populations. Other commentators have suggested that there is no impact on suicide trends, and pointed out that rates of self harm are rising, not falling (3). Long-term incapacity due to depression in the UK continued to rise throughout the 1990s (4). Yours, Joanna Moncrieff. References: 1) Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. BMJ 2003; 326:1008-11 2) Furukawa TA, McGuire H, Barbui C. Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review. BMJ 2002;325:991-995. 3) Van Praag HM Why has the antidepressant era not shown a significant drop in suicide rates? Crisis 2002; 23:77-82 4) Moncrieff J, Pommerleau J. Trends in sickness benefits in Great Britain and the contribution of mental disorders. Journal of Public Health Medicine 2000;22:59-67. Competing interests: None declared |
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Brian M Draper, Conjoint Associate Professor, University of NSW, Sydney Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Randwick, NSW, 2031, Australia
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Hall et al suggest that reductions in suicide rates in older people in Australia could be attributed to their increased exposure to antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs) [1]. Of course, reduction of suicide rates due to improved treatment of depression is an outcome we all hope could occur. But the associations appear to be attribute possible causality inappropriately. According to the Australian Bureau of Statistics, there has been a gradual reduction in suicide rates in persons over the age of 40 in Australia since 1961-65, the peak period of suicide deaths for these age groups since the Great Depression. This is true for each 5-year age group from age 40 years over, and for both men and women. Indeed, in most age groups, the greatest reduction occurred in the period before 1990. For example in 1961-65, suicide rates in men aged 45-49 years were 34.9 per 100 000 people and in men aged 50-54 years 39.4 per 100 000 people. In 1986-90 these had dropped to 23.5 and 24.7 per 100 000 respectively (or 24.1 for the ten year group 45-54 quoted by Hall et al). Yet by 1996-2000 this had only dropped to 23.8 per 100 000. Similarly if we examine males aged 55-64 years, from 1961-65 to 1986-90 suicide rates dropped from 37.8 per 100 000 to 25.1 per 100 000, and to 20.7 in 1996-2000. This scale of pre-1990 suicide rate reductions is also found in females. For example in 1961-65, the suicide rates of females aged 65-69 was 18.2 per 100 000 and in those aged 70-74, 15.1 per 100 000, which dropped to 8.5 and 8.2 per 100 000 respectively in 1986-90 (or 8.4 for the ten year group 65-74 quoted by Hall et al). By 1996-2000 this had only reduced to 5.8 per 100 000 [2]. Clearly there were more substantial historical trends of suicide reduction long before the introduction of the SSRIs. The reasons for this reduction are unclear but may include improved physical health in middle age and old age, better community services for the disabled to enhance independence, and greater financial security in later life, all of which are risk factors for depression in older people. Improved detection and treatment of depression is unlikely to be as effective in preventing suicide as the prevention of depression itself. While it is important to examine these types of associations, a broader appreciation of the issues involved would provide a more balanced report. 1. Hall DW, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. Br. Med. J. 2003;326:1008-1012. 2. Australian Bureau of Statistics. Suicides 1921-1998. ABS Catalogue No. 3309.0, Canberra, 2000 Competing interests: None declared |
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David Gunnell, senior lecturer in epidemiology and public health medicine Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8, Nicos Middleton, Jonathan AC Sterne
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Hall et al's analysis of the beneficial effects on suicide of higher levels of antidepressant prescribing(1) in Australia may be misleading. Their suggestion of such profound potential effects of increased levels of antidepressant prescribing on population suicide rates contrasts with those of a recent review of antidepressant trials.(2) In Khan's review, perhaps surprisingly, suicide rates were no different in those treated with placebo than those receiving antidepressants. The authors' approach of correlating age- and sex-specific prescribing, and changes in prescribing, with changes in each age group's suicide rate is unusual. Indeed in five of the sixteen age- and sex- groups (younger males and females) Hall studied, increases in prescribing were actually accompanied by rises in suicide. A more conventional, and direct, approach would have been to contrast trends in age-specific prescribing with trends in suicide. Inspection of UK data on antidepressant prescribing (1976-1998)(3) and Office for National Statistics data on suicide and undetermined deaths(4) for England and Wales reveals that a 3-4 fold rise in antidepressant prescribing in 20-29 and 30-39 old males has been accompanied by 50% rises in their suicide rates (see attached figure). Even in 40-54 year olds, an age group in which an almost four fold increase in prescribing occurred, suicide rates have remained relatively stable. It is only amongst those aged 55+ that any effects are seen - these groups do indeed show an accelerated rate of decline in the late 1980s when antidepressant prescribing increased dramatically. In women, declines in suicide in all but 15-19 year olds have been accompanied by rises in antidepressant prescribing, however, the rise in prescribing in the late 1980s was not accompanied by any noticeable change in trends in their rates of suicide. There are well-recognised problems with interpreting such ecological data. Analyses such as Hall's and others,(5) where the effects of only single factors are investigated, may produce misleading results. Many factors may influence population trends in suicide.(4) It is of note, however, that in a recent time series analysis taking account of such factors, we found some evidence that rises in antidepressant prescribing in the elderly may indeed have had some beneficial effects on their suicide rates.(4) David Gunnell1 Nicos Middleton1 Jonathan Sterne1 1Department of Social Medicine, Canynge Hall, Whiteladies Road, Bristol BS8 2PR Email: d.j.gunnell@bristol.ac.uk Fax: 0117 9287325 Phone: 0117 9287253 References 1. Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. BMJ 2003;326:1008-11 2. Khan A, Khan S, Kolts R, Brown WA Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry 2003;160:790-2. 3. Middleton N, Gunnell D, Whitley E, Dorling D, Frankel S. Secular trends in antidepressant prescribing in the UK, 1975-1997. J Pub Health Med 2001;23:262-267 4. Gunnell D, Middleton N, Whitley E, Frankel S, Dorling D. Why are suicide rates rising in young men but falling in the elderly? - a time series analysis of trends in England and Wales 1950-1998. Soc Sci Med (in press 2003) 5. Isaacson G Suicide prevention - a medical breakthrough? Acta Psychiatr Scand 2000;102:113-7.
Competing interests: None declared |
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Wayne D. hall, Professor and Director, Office of Public Policy and Ethics Institute for Molecular Bioscience, University of Queensland, St Lucia, Q, 4072, Wayne Hall, Andrea Mant, Phillip Mitchell, Valerie Rendle, Ian Hickie and Peter McManus
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Responses to Our Critics We welcome the debate that our paper has prompted. The following are our responses to the various criticisms made of our paper in the Rapid Responses. 1. Misconstruals of our views A number of critics (De Leo, Draper, Verberne) attributed to us views that are not expressed in our paper, namely, that the decline in suicide in Australia between 1990 and 2001 was wholly due to the pharmacological effects of increased antidepressant prescribing, and that suicide rates are not affected by the availability of methods of suicide, unemployment, alcohol consumption, social factors etc. It should be clear from the factors that we considered as alternative explanations of the trend that we accept neither of these views. We explicitly argued that: "the association that we observed between antidepressant prescribing and suicide may reflect increased recognition, diagnosis and treatment of depression by general practitioners as much as any pharmacological effects of antidepressant medication"(p1012). The observation that suicide rates declined in older women before the antidepressant era would only undermine our paper if we had claimed that all declines in suicide were attributable to antidepressant prescribing. We accept that there are multiple causes of suicide; that integrated efforts are required to reduce suicide deaths; and that the prescribing of antidepressants to people who are depressed is not sufficient although it should be part of an integrated response. Nor do we claim that reducing suicide is the only goal of antidepressants prescribing (Allen). Improved quality of life is an important goal of treatment in depression. 2. Methods of Data Analysis Ankarberg and De Leo argue that antidepressants did not decrease suicide rates between 1990 and 2001 because there was no decrease in young males among whom antidepressant prescribing increased over the same period (although from a very low base rate). It is always possible to select data points that run counter to a statistical trend; that’s why we use statistics. The critical finding was the relationship between exposure to antidepressants across age groups in both sexes. Antidepressants are clearly not all that influences in suicides among young males. We noted in our paper that others have argued that the increased suicide rate in young males has been driven by rising unemployment. De Leo has argued that correlation coefficients calculated using the base rate as covariate produce a different result, namely, no correlation between change in antidepressant prescribing and suicide trend. This analysis would answer a different question: whether after taking account of baseline antidepressant use, the increased rate of prescribing predicted suicide trend. We do not think that this is an appropriate analysis because controlling for the base rate of prescribing removes the effects of antidepressant exposure which we found is related to change in suicide rate. De Leo also argues that larger correlation between antidepressant exposure and decline in suicide than between change in antidepressant prescribing and suicide decline signals a spurious result. We think the more likely explanation is statistical: a score based on an average of DDD over three time points will be more reliable than a score based on a difference in DDD over the same period. Senn has argued that the relationship we reported was not robust to method of statistical analysis. He briefly reports two Poisson regression analyses, only one of which found a similar relationship to the one that we reported. We disagree that our results are not robust to method of analysis. We originally performed a Poisson regression analysis of suicide rates and calculated a correlation between the logarithm of the incident rate ratio (IRR) for the two periods and the two measures of DDD across the eight age groups for each and sex. This analysis produced the same patterns of result as the analysis that we reported in our paper. The correlations between log IRR and average DDD were -0.81 (p < 0.05) in females and –0.79 in males (p < 0.05) while the correlations with change in DDDs was –0.81 in females (p < 0.05) and –0.43 in males (not statistically significant). We reported the correlations between the difference in suicide rate and the two DDD measures because we believed that this analysis would be more easily understood than one based on log IRRs. Moncrieff made a number of criticisms of the DDD measure. She argued that we should have used RR rather than absolute changes in DDD. We disagree: the questions of interest were about the relationship between suicide and overall exposure to antidepressants and change in exposure to antidepressants over time. A ratio of DDDs would provide an alternative measure of change in exposure but it would not measure overall antidepressant exposure. She also argued that DDD is a potentially misleading measure because it will underestimate prescribing levels of tricyclic antidepressants in the elderly. We accept that this may be the case but believe that, if anything, this would underestimate any correlation between antidepressant prescribing and suicide trend by underestimating elderly exposure to antidepressants. Alternative Explanations of Our Findings Fabrication of Data Bagnall implies that our findings have been fabricated to serve the interests of the pharmaceutical industry because several of the authors (AM, PM and IB) have accepted funding from the industry. No evidence is offered for this ad hominem attack or for the assertion that a history of pharmaceutical industry funding is incompatible with conducting valid scientific research. Changes in Methods of Suicide Blisker suggested a more plausible alternative explanation of our findings, namely, that it : "could reflect a proportionately greater reliance upon antidepressant overdose as a suicide method in older age groups. If the proportion of individuals using antidepressant overdose as a suicide method increases with age, and if individuals in these older age groups are unlikely to substitute other methods, one would expect that improved safety of antidepressant medication would have its greatest impact upon suicide rates in older age groups". De Leo made the same point, citing in support of this hypothesis Australian data that there had been a larger proportionate decline in suicides by drug overdoses among older than younger adults. This is a plausible hypothesis that cannot be easily excluded because detailed data are not available on changes in method of suicide over time by age and sex. The Australian Bureau of Statistics (2003) reports that the proportion of suicides in which poisoning was the method among males declined from 11.3% in 1991 to 7.8% in 2001. The decline was even larger among females, from 35.1% to 25.8%. The small proportion of older male suicide deaths by poisoning using drugs makes a decrease in self-poisoning an unlikely explanation of age-related changes in suicides among men. The fact that the decline in suicide rate was greater among men than women is also inconsistent with Blisker and De Leo’s hypothesis because there was a greater decline in self-poisoning among women than men. De Leo and colleagues (2001) report that in 1997 all forms of poisoning by solids or liquids accounted for only 6% of suicides among males aged over 65 years compared with 33% of suicide deaths in females. The most common methods of suicide among males in this age group were: hanging (30%), carbon monoxide poisoning (27%) and firearms (15%). Omission of other factors Sheikal argued that our results may have been different if we had included data on the use of other treatments e.g. ECT and psychological interventions. We think this unlikely for ECT because this is a specialist intervention that has never been widely used by general practitioners, it is not often used in specialist settings and its frequency of use has probably declined over the study period. We agree that the increased use of psychological interventions by GPs has probably played a role. We argued as much in our paper. Ineffectiveness of Antidepressants in Reducing Suicide Ankarberg and De Leo argue that antidepressants do not reduce suicide because meta-analyses of placebo controlled RCTs have not shown a lower rate of suicide among patients receiving antidepressants than in those receiving placebos. We were aware of these data but believe that they are of limited value in assessing the impact of antidepressant prescribing on suicide in the population because most of these studies involved follows up of less than six months and patients at risk of suicide are often excluded from placebo-controlled trials. Allen and Bagnall claim that SSRIs may increase suicide risk in the short-term in individual patients. This is not supported by the meta-analyses of controlled trials and is not supported by our data. This possibility is not inconsistent with a correlation between antidepressant prescribing and suicide deaths because rare adverse events that affect individuals do not preclude an aggregate benefit from antidepressants at the population level. Ineffectiveness of GP Management of Depression Allen argues from his personal experience that antidepressants work but he is sceptical that psychological treatments are effective for depression. We agree that patients with severe depression require more than talk but the evidence is that for mild to moderately severe depression psychological interventions can be as effective as medication. Psychological interventions inevitably accompany medication as well. Allen also argues that GPs do not have skills to dispense antidepressants. We agree that more serious cases of depression require specialist treatment but GPs provide an important gateway to specialist psychiatric care and, when appropriately trained and supported, they can diagnose and manage a range of the more common depression of mild to moderate severity. Conclusion We agree with our critics that one has to be cautious in interpreting time series data. As we acknowledged in our article. We do not claim to have proved that increased antidepressant prescribing was responsible for the decline observed in suicide deaths in Australia between 1991 and 2000. Any such inference will require a convergence of evidence from a variety of different studies. . We hope that our paper will encourage other investigators to test relationships between antidepressant prescribing and suicide in other countries. It would be of particular interest to see if the pattern of decline in suicide deaths that we observed in Australia has also occurred in countries that have not seen an increase in antidepressant prescribing over the same period. Australian Bureau of Statistics. Information Paper Suicides 2001. Catalogue No. 3309.0.55.001. Australian Bureau of Statistics, 2003. De Leo D, Hickey PA, Neulinger K and Cantor CH. Ageing and Suicide. Commonwealth Department of Health and Aged Care, Canberra, 2001. Competing interests: Disclosures re Competing Interests: Funding for the project was provided by beyondblue: the National Depression Initiative; Wayne Hall's time was funded by the Strategic Fund of the ViceChancellor, University of Queensland. Wayne Hall has no competing interests to declare. Andrea Mant was a consultant on Quality Use of Medicines to Merck, Sharp and Dohme Australia (1997), has been a member of advisory boards for Pfizer and Sanofi-Synthelabo (1999-2000) and was sponsored to attend Global Health Care 2000 Conference (Eli-Lilly). Philip Mitchell has received research funding and honoraria in the last five years from several pharmaceutical companies which manufacture antidepressant medications. Valerie Rendle has no competing interests to declare. Ian Hickie has received research funding and honoraria in the last five years from several pharmaceutical companies for conduct of General Practice training programs, notably SPHERE: A National Depression Project. Pharmaceutical industry support (Wyeth) has been received for participation in international meetings detailing the economic and social costs of depression. Peter McManus has no competing interests to declare. |
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Thomas J P Verberne, none 14 Crampton Crescent Rosanna VIC 3084 Australia
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The bracketing of my name with the names of professors De Leo and Draper as a critic who attributed to the authors views not expressed in their paper must be due to a word processing error. I am sure that when they reread my letter, they will agree. Thomas J P Verberne Competing interests: None declared |
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