Recent trends in the use of antidepressant drugs in Australia, 1990-1998

Abstract

To review trends in antidepressant use in Australia, the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee, Department of Health and Aged Care, convened a working group in 1998. The working group, which comprised representatives from the DUSC and from the Australian Pharmaceutical Manufacturers Association (APMA), reviewed Australian and international data on antidepressant sales and dispensing. The aim was to determine patterns of antidepressant use in Australia between 1990 and 1998 and to compare Australian patterns with those in similar developed countries. To assist in interpretation of Australian drug use trends, the group reviewed changes in both the frequency of general practice patient encounters for depression and in population-based prevalence estimates for affective disorders.

Methods

Prescription and sales data

Prescription dispensing data were obtained from the database maintained by the DUSC that monitors the dispensing of prescription medicines through community pharmacies in Australia.² No data on public hospital use are included in this database. The measurement units used are either prescription volumes or the number of defined daily doses (DDDs) per 1000 population per day. The DDD is based on the assumed average daily dose of the drug when used for its main indication by adults. It is the unit approved by the World Health Organization (WHO) for drug use studies, and allows for comparisons independent of differences in price, preparation and quantity per prescription.³ Within the data on dispensing of antidepressant drugs subsidised by the Pharmaceutical Benefits Scheme (PBS), it is also possible to determine the major specialty of the prescribing doctor.

Data on total sales of antidepressants from wholesalers to retail and hospital pharmacies for all countries, except Sweden, were obtained from IMS Health Incorporated. IMS Health is the leading international provider of information on drug usage to the pharmaceutical and healthcare industries.⁴ Data were retrieved as kilograms of active ingredient and then converted to DDDs per 1000 population per day. Excluded were the use of lithium, Hypericum (St John's wort) or tryptophan, and combinations involving these drugs or their active constituents. Utilisation data for Sweden, where separate local arrangements apply, were supplied by the Swedish Association of the Pharmaceutical Industry (LIF).

The 1999 WHO defined daily doses (DDDs) were used in calculations. Drugs unique to particular markets that did not have DDDs available were provisionally assigned values using standard references and information provided by drug information centres in the countries involved.⁵

Prescriber surveys

Community health surveys

The 1997 National Survey of Mental Health and Wellbeing of Adults was also conducted by the Australian Bureau of Statistics and used a representative sample of people aged 18 years or over living in private dwellings.¹⁰ The survey was interview-based with a diagnostic component administered through a modified version of the WHO Composite International Diagnostic Interview (CIDI). The CIDI translates the criteria of the Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV),¹¹ and the International classification of diseases, 10th edition (ICD-10),¹² into sets of questions that can be readily answered by the general adult population. Specific combinations of symptoms may indicate a specific mental disorder.

Results

Antidepressant use in Australia

The market uptake of the SSRIs has been rapid and accompanied by a decrease of only 25% in the use of the TCAs. Other new agents included moclobemide (a reversible monoamine oxidase type A inhibitor), nefazodone (a 5-HT₂ antagonist) and venlafaxine (a serotonin-noradrenaline reuptake inhibitor).

The 10 most commonly dispensed antidepressants in Australia in 1998 were, in descending order, sertraline, dothiepin, paroxetine, amitriptyline, fluoxetine, doxepin, moclobemide, imipramine, venlafaxine and citalopram. Of these, only the four tricyclic antidepressants were on the market in 1990, with dothiepin alone maintaining or improving its position over this period.

Of the PBS-subsidised prescriptions dispensed for antidepressants in 1998, 85% were written by GPs, while 11.2% were written by psychiatrists.

International comparisons

For these same countries in 1998, Box 3 shows the percentage split (based on DDDs/1000 population per day) of the antidepressant market by drug class. There was considerable variability in the percentage that TCAs represented of overall antidepressant use, from a low level of 11% in Sweden through to a high of 67% in Germany. Australia, Canada and France had a similar profile, with TCAs representing about 20% of antidepressant use.

Venlafaxine was marketed in all eight of the countries surveyed and ranged between 1.5% and 5.2% of the total use. Mianserin had a low level of use in most countries, except for France and Italy, where it represented about 4% of antidepressant use. It was not available in North America. Similarly, moclobemide had a low level of use in most countries, except in Australia, where it represented 12% of the antidepressant market.

Prescriber surveys

Comparisons with age and sex demographics for total general practice encounters (women, 58.7%) suggest that female patients were over-represented at encounters for depression.

The most frequent patient age group in encounters at which a tricyclic antidepressant was prescribed was 45-64 years (38%), whereas for encounters at which SSRIs were prescribed it was 25-44 years (43%). Sex distribution was similar for both drug groups, with about a third of the patients being men.

Depression was the most common problem for which TCAs and SSRIs were prescribed in 1998-99, although the proportion of TCAs prescribed for depression (48.8% [95% CI, 44.3%-53.3%]) was lower than that of SSRIs (81.9% [95% CI, 79.7%- 84.1%]). Other specific problems managed with TCAs were sleep disturbance (7%), anxiety (5%) and back complaints (4.5%). For the SSRIs, these were anxiety (5.8%) and phobia/compulsive disorder (1.7%).

When used for depressive disorders, TCAs had a prescribed daily dose consistently lower than the WHO DDD. The prescribed daily doses and DDDs for the most commonly dispensed TCAs were amitriptyline (mean, 59 mg; median, 50 mg; DDD, 75 mg), doxepin (mean, 61 mg; median, 50 mg; DDD, 100 mg) and dothiepin (mean, 85 mg; median, 75 mg; DDD, 150 mg). The prescribed daily doses for the most commonly dispensed SSRIs were much closer to the DDD: fluoxetine (mean, 24 mg; median, 20 mg; DDD, 20 mg), paroxetine (mean, 23 mg; median, 20 mg; DDD, 20 mg) and sertraline (mean, 72 mg; median, 50 mg; DDD, 50 mg).

Community health surveys

Although based on self-reports, household surveys conducted by the Australian Bureau of Statistics in 1989-90 and 1995 identified marked changes in the number of people reporting current or previous depression. In the 1995 National Health Survey, 8.1 persons per 1000 population reported depression as a long term condition, compared with 2.8 persons per 1000 in the 1989-90 survey. For depression as a recent illness, 11.4 per 1000 population reported this in 1995, compared with 5.8 per 1000 in 1989-90.^8,9

Discussion

Prominent among the likely reasons for this change are increased community awareness of depression as an important health issue, and attempts, most notably through government and community campaigns, to reduce the stigma of mental illness and the gaps in professional expertise inhibiting adequate recognition and treatment of depression.^16,17

Coincident with these campaigns, important treatment recommendations were released in the United Kingdom in 1992 (the Royal College of General Practitioners and the Royal College of Psychiatrists) and, in the United States, in 1993 (Agency for Health Care Policy and Research).^13,18 In Australia, the Psychotropic drug guidelines¹⁹ are the endorsed national standard, and the National Health and Medical Research Council has published clinical practice guidelines for managing depression in young people.^20,21

The 1995 Australian National Health Survey showed that the number of people reporting depression as a recent and/or long term condition had nearly doubled compared with the earlier survey conducted in 1989-90. Such a change in the true underlying prevalence of disease is unlikely over a relatively short period of time, and the increase is far more likely to reflect a greater awareness of depression, with patients being more comfortable about coming forward for help and doctors, particularly in general practice, being more willing to provide it. This increased awareness of depression by doctors and patients, together with the availability and promotion of new drug therapy options (between 1990 and 1998, five SSRIs have been approved for PBS subsidy together with moclobemide, venlafaxine and nefazodone), accounts for the rise from the tenth to the fourth most common problem managed in general practice between 1990-91 and 1998-99. In 1998-99, encounters for depression were also more likely to generate a prescription for an antidepressant.

This change is reflected in drug utilisation statistics. The market uptake of the SSRIs has been rapid and, remarkably, accompanied by only a relatively small decrease in the use of the TCAs. As a result, the overall antidepressant market has expanded greatly, with utilisation (as defined by DDDs/1000 population per day) being nearly three times greater in 1998 than in 1990. Prescription rates, however, have risen only 60% over that time, as the newer antidepressants are more likely to be dosed closer to the DDD than the older tricyclic antidepressants. TCAs are prescribed for sleep disturbance in a small proportion (7%) of patients, which is not the case for SSRIs.

Most developed countries have seen similar trends, with sales in Australia consistent with US sales and slightly higher than those in the UK. The percentage that the SSRIs represented of total antidepressant use in Australia in 1998 was similar to that in the United Kingdom.

The considerably lower levels of antidepressant use in Germany are probably related to Germany's strong tradition of use of complementary medicines (substantial use of Hypericum preparations [St John's wort] were not included in the comparisons); and the lower levels in Italy may be because, in 1994-98, SSRIs were not reimbursed by the national health system in Italy, but were fully paid for by the patient (Dr Alberto Vaccheri, Associate Professor, Department of Pharmacology, University of Bologna, personal communication, June 1999).

Although there are interesting differences between countries, the rapid uptake of the new antidepressants is likely to have been driven by increased awareness, together with the availability and promotion of new therapies. The drug utilisation patterns, supported by evidence from population and general practice surveys, showed that there has been growth in the actual market rather than just redistribution within the market. Public health benefits of this major change in drug use (eg, reductions in suicide rates) are anticipated in the long term, but measuring population-level outcomes from changes will not be easy.

Acknowledgements

Disclosure: Philip B Mitchell has been a member of scientific advisory boards for Eli Lilly, SmithKline Beecham and Wyeth.

References

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(Received 5 May, accepted 31 Aug, 2000)

Authors' details

South Eastern Sydney Area Health Service, Sydney, NSW.
Andrea Mant, MD, FRACGP, MA, Area Adviser, Quality Use of Medicines; and Associate Professor, School of Community Medicine, University of New South Wales, Sydney, NSW.

School of Psychiatry, University of New South Wales, NSW.
Philip B Mitchell, MD, FRANZCP, FRCPsych, Professor; and Administrative Director, Mood Disorders Unit, Prince of Wales Hospital, Sydney, NSW.

Health Economics and Outcomes Research, Eli Lilly Australia Pty Ltd, Sydney, NSW.
William S Montgomery, BPharm, DipHospPharm, GradCertHealthEcon, Health Outcomes Research Manager.

Department of General Practice, University of Adelaide, Adelaide, SA.
John Marley, MD, MB ChB, Professor.

Health Economics and Pricing Department, SmithKline Beecham (Australia) Pty Ltd, Melbourne, VIC.
Merran E Auland, PhD, Health Economist.

No reprints will be avaliable from the authors.
Correspondence: Mr P McManus, Secretary, Drug Utilisation Sub-Committee, Mail Drop Point 83, Department of Health and Aged Care, GPO Box 9848, Canberra, ACT 2601.
peter.mcmanusAThealth.gov.au

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