Faculty of Medicine, University of Iceland
Faculty of Economics and Business Administration,University of Iceland
Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Correspondence: Tómas Helgason, 4 Midleiti, IS-103 Reykjavik, Iceland. Tel: +354 5532287; e-mail: tomashe{at}isholf.is
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ABSTRACT |
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Aims To test the public health impact of the escalating sales of antidepressants.
Method Nationwide data from Iceland are used as an example to study the effect of sales of antidepressants on suicide, disability, hospital admissions and out-patient visits.
Results Sales of antidepressants increased from 8.4 daily defined doses per 1000 inhabitants per day in 1975 to 72.7 in 2000, which is a user prevalence of 8.7% for the adult population. Suicide rates fluctuated during 19502000 but did not show any definite trend. Rates for out-patient visits increased slightly over the period 19892000 and admission rates increased even more. The prevalence of disability due to depressive and anxiety disorders has notdecreased over the past 25 years.
Conclusions The dramatic increase in the sales of antidepressants has not had any marked impact on the selected public health measures. Obviously, better treatment for depressive disorders is still needed in order to reduce the burden caused by them.
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INTRODUCTION |
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widely publicized emphasis on recognition and treating depression and...development of many new pharmacotherapies have contributed to explosive growth in antidepressant prescribing and increasing pharmacy costs for health plans (Williams et al,2000).
Major depressive disorder is the second leading cause of disability-adjusted life-years in developed regions of the world (Murray & Lopez, 1996) and antidepressants, the third-ranking therapy class worldwide, experienced an 18% sales growth in 2000, with North America being the dominant market (IMS Health, 2002). However, the question remains: has this had any impact on public health and the burden of depression? Analysis of official data from Iceland, with its extensive use of antidepressants, can contribute to answering this question. We have examined the data in order to address the following questions: how much has the sale of antidepressants increased since SSRIs were introduced in Iceland by the end of 1988, and what is the proportional increase in the sale of these and other more recent antidepressants; has the increased use of antidepressants affected the number of psychiatric out-patient visits and the extent of hospital treatment; and has the increased use of antidepressants affected suicide rates or the prevalence of disability?
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METHOD |
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Data
The following nationwide data were collected from a range of official
sources.
Until 1993, very few children and adolescents under the age of 15 years
were prescribed antidepressants, and in that same year only 0.8% of
prescriptions were issued to children under this age. According to a recent
limited prescription survey, 6.7% of the antidepressants were filled for this
age group (Skrsla,
1999). Therefore a 1% annual increase was assumed and deducted
from the total quantities sold when estimating the number of daily defined
doses per 1000 inhabitants aged 15 years or more during 19942000.
Statistical analysis
For analyses of time series count data, a quasi-Poisson model was used. The
logarithm of expected counts is expressed by
Equation (1):
![]() | (1) |
![]() | (2) |
The possibility of autocorrelation was addressed by inclusion of autoregressive terms (Cameron & Trivedi, 1998). The statistical program R was used for numerical calculations (Ihaka & Gentleman, 1996).
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RESULTS |
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Official figures on the sales of antidepressants have been available only since 1975 and are shown in Fig. 1, along with annual suicide rates and per capita sales of alcohol for the period 19502000. An example of model output according to Equation (1) is given in Table 2, which suggests that the number of suicides has increased slightly more than the corresponding increase in population and, by spectral analysis, estimates of the autoregressive parameters (0.45 and -0.33) suggest a cycle of about 56 years. The data do not allow us to determine whether this is due to some events within a year or whether there are genuine cycles in the process. The standard errors in Table 2 are corrected for overdispersion. Residual analysis showed that the process is remarkably constant over a 50-year period. The scaled residuals showed no autocorrelation after including the two autoregressive terms in the model. A Ramsey-RESET test did not indicate that the model was wrongly specified (P=0.98). Consequently, there is no indication that a trend or some simple function of time is missing from the model as an explanatory variable, particularly not the increased sales of antidepressants.
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Figure 2 shows a graph of
standardised residuals of the model. A possible explanatory variable that
might add information on the frequency of suicides should have something in
common with what is not explained by the model, i.e. the residuals. To
illustrate this point, a graph of the annual average sales of pure alcohol per
inhabitant is also shown in Fig.
2. The Ramsey-RESET test did not suggest that the model was
wrongly specified. To illustrate this further the model was reestimated with
alcohol consumption per capita and its lagged value added to the model. The
impact was only marginal (a likelihood ratio test statistic of 0.42;
2=0.66; d.f.=2), which is not surprising considering the
result of the Ramsey-RESET test.
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The population in the year 2000 was about 283 000 and the average suicide rate was 11/100 000, so the expected annual number of suicides is around 30. The over-dispersion coefficient in the model containing autoregressive terms is approximately 1.5, therefore the standard deviation of the yearly number of suicides is the square root of 1.5x30, which is about 7. In a model without autoregressive terms the overdispersion is about 1.9, which gives a standard deviation in the region of 8. Thus, the autoregressive parameters have limited impact on predicting the number of suicides.
Sales of antidepressants and psychiatric out-patient visits and hospital admissions
In spite of the dramatic increase in the sales of antidepressants, the
rates of psychiatric out-patient consultations and in-patient treatment for
depressive disorders increased (Fig.
3). After correcting for the increase in the population aged 15
years or more, the number of patients admitted increased by about 3.9%
annually. Similarly, after correcting for the increase in population the
admission rates increased by 5.4% per year (i.e. each patient was admitted
more often). Furthermore, the number of out-patient consultations increased by
2% per year during the period 19892000. The total duration of
in-patient treatment for depressive disorders per 100 inhabitants decreased by
1.1% per year whereas that for psychiatric disorders in general decreased by
3.6% annually as the number of available beds decreased.
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Disability
The proportion of the general population claiming disability pension
because of depressive and anxiety disorders increased from 0.4% to 0.7%, as it
did for other disorders over the 25-year period of 19762001; however,
it remained similar as a proportion of all disability (i.e. about 13%).
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DISCUSSION |
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Sales of antidepressants and the prevalence of depressive disorders
Recently, the International Consensus Group on Depression and Anxiety
stated that depression was currently underrecognised and undertreated,
particularly in young adults (Ballenger
et al, 1999). The results of the present study hardly
support this as regards treatment with antidepressants. The sales of
antidepressants in Iceland in the year 2000 corresponded to a user prevalence
of 8.7% among those aged 15 years or more, which is within the range of
estimates for the community prevalence of depressive disorders: 410%
among adults (Bebbington et al,
1998; Helgason,
1990). Depressive disorders cause considerable impairment, result
in increased mortality, reduce the health-related quality of life
(Simon et al, 1998)
and are costly for the patients, their families and society. The direct cost
of treating depressive disorders in Iceland, the population of which is
approximately one-thousandth of that in the USA, was estimated to be
equivalent to £18.6 million in 1998
(Skrsla, 1999) and
about 27%, of this amount was ascribed to antidepressants, mainly SSRIs.
The prevalence of subsyndromal depression or of depressive symptoms is considerably higher than that of depressive disorders, being 1625% (Helgason, 1990). Depressive disorders and symptoms are very common in primary care and are often comorbid with physical disorders (Kisely & Goldberg, 1996); they are also mixed with anxiety disorders, for which antidepressants have been used increasingly in recent years.
During the past 1015 years new generations of antidepressants have been developed and marketed energetically. At the same time, awareness campaigns have been launched to combat depression (Paykel et al, 1998) and to prevent suicide in a number of countries (Taylor et al, 1997). In addition, guidelines for treating depressive disorders have been issued (American Psychiatric Association, 2000). These developments might have been expected to have a public health impact by reducing disability, morbidity and mortality due to depressive disorders, even more so as the new medications are simpler to administer and more likely to be given in adequate dosages than tricyclic antidepressants. However, the cost for society has not been reduced and the impact on public health is limited.
Far fewer antidepressants are taken than are sold (prescribed), therefore
prevalence estimates based on sales data are too high due to limited
compliance. In a recent community survey the self-reported use of
antidepressants (in DDD/1000/day) was estimated to correspond to about 54% of
the official sales figures (Helgason et
al, 2003). The reasons for many of the prescriptions are not
clear, as primary care physicians have probably not diagnosed depressive
disorder in more than 4050% of patients prescribed antidepressants
(Skrsla, 1999;
Ornstein et al,
2000). It should be noted, however, that antidepressants are being
used increasingly for other disorders, such as some anxiety disorders and
chronic pain.
Admissions, out-patient visits and disability
Admission rates for in-patient treatment of depressive disorders have
increased, partly because of more readmissions and partly because more
patients are admitted. The number of in-patient days used for depressive
disorders has decreased insignificantly but in contrast, the decrease in
in-patient days for psychiatric disorders in general has been quite marked. At
the same time as these trends were occurring, the availability of psychiatric
hospital beds was also decreasing. The increased annual admission rate may
indicate increasing acceptance of treatment and decreasing stigmatisation, as
well as a possible lower admission threshold for depressive disorders because
beds for other disorders might have been freed up owing to the tendency to
treat people with psychosis in the community. The rates for psychiatric
out-patient visits increased, thus it is conceivable that the new
antidepressants have not stopped the need to refer intractable cases of
depression for speciality treatment. It has been found in clinical studies
that adequate treatment can be expected to alleviate physical and psychosocial
impairment in patients with depression and to improve their quality of life
(Simon et al, 1998).
Despite extensive pharmacological treatment, the prevalence rates for
disability due to depressive and anxiety disorders increased, although not as
a proportion of total disability. It should be noted that the increased
prevalence of disability pension between 1996 and 2001 is related to changes
in disability assessment.
Suicide rates
Suicide rates in Iceland have fluctuated roughly as an autoregressive
Poisson process with a dispersion coefficient of 1.5 during the latter half of
the 20th century, remaining on average about 11/100 000. The age and gender
distribution of those who died by suicide may have changed during this period,
but the overall rates have not been affected by the sales of antidepressants,
which have increased ninefold since 1975. It is unlikely, according to our
findings, that a reduction in the sales of antidepressants would affect the
rates of psychiatric service use and suicide.
Unemployment has not been a problem in Iceland during the study period, with less than 1% of the labour force being out of work most of the time. However, in 1969 unemployment rose to 2.5%, only to decrease again and then rise to 5% in 1995. In 1999 it had fallen once more to less than 2%. One-third or less of those unemployed were out of work for more than 6 months (Statistics Iceland, 2002). The Ramsey-RESET test (Gujarati, 1995) does not indicate that unemployment and other unknown variables have had an effect on the number of deaths by suicide.
One of the main features of time series models is to filter out trends and cycles. It is conceivable that alcohol consumption, unemployment and other variables affect suicide rates. If that is the case, the residual diagnostics indicate that they are already sufficiently included in the trend-and-cycle component of the model. Thus, it is not likely that a counteracting effect of alcohol and antidepressants can be invoked as an explanation for not finding any effect of the huge increase in antidepressant use on suicide rates in Iceland.
Suicide rates in the population are a very crude measure of the public health impact of antidepressant medication. Suicide rates have decreased during the 1990s in some countries, especially in those with national strategies (Taylor et al, 1997) aimed at preventing suicide, such as the UK (McClure, 2000), Finland, Norway and Sweden (Isacsson, 2000), in Denmark (Isacsson, 2000), which did not have such a strategy (Taylor et al, 1997), and in the USA (Maris, 2002). However, it may be noted that the suicide rate in Norway has remained unchanged at the 1980 level since 1995 (Retterstöl et al, 2002), in spite of increasing sales of antidepressants. The results of a Swedish study suggested that the increasing use of antidepressants was a contributing factor to the decreasing suicide rates (Isacsson, 2000). The results of the present study do not support this suggestion because a hypothetical missing explanatory variable (i.e. increased sales of antidepressants) did not correlate with the residuals of the statistical model used. Although clinical psychiatrists are convinced that suicides can be prevented in individual patients by adequate treatment, it has been difficult to prove in large studies (Khan et al, 2000).
It is of major importance to study the effects of the extensive prescribing of antidepressants to the large number of people obtaining them who do not have a diagnosed depressive disorder. Data on newer pharmacotherapies for patients with subsyndromal or mixed anxiety-depression and for special populations such as children and adolescents are insufficient to guide treatment decisions (Agency for Health Care Policy and Research, 1999). The results of such studies could help to elucidate whether antidepressants improve the recipients' quality of life and/or prevent later development of major depression or other impairment.
There are no signs that the rapidly escalating use of antidepressants is reducing the burden of depressive disorders (Moncrieff, 2002). The present study has not revealed any marked impact of the dramatic increase in sales of antidepressants on psychiatric aspects of public health at the macro-level, except bringing the most common mental disorders into the mainstream of medical treatment for the benefit of patients, but at a substantial increase in medication cost. This has possibly reduced stigmatisation and brought about an increased acceptance of the need for treatment, as is reflected in the growing number of patients admitted to hospital psychiatric departments. But because the public health indicators studied are based on administrative data, more detailed studies on distress, quality of life, work performance and short-term absenteeism might reveal a greater impact (Simon et al, 1998).
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication March 14, 2003. Revision received August 13, 2003. Accepted for publication September 3, 2003.
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