1 Selective serotonin reuptake inhibitors (SSRI) – sales, withdrawal ...

126 M. Nielsen and P. Gøtzsche / An analysis of psychotropic drug sales
introduced and expectations were high regarding efficacy and safety [2]. Benzodiazepines and SSRIs are
partly registered for the same indications, for example anxiety [3].
Several studies have described an increasing use of SSRIs and a decreasing use of benzodiazepines.
A few studies have looked at overall usage [1] and others have focused on specific drug groups [4, 5].
The OECD (Organisation for Economic Co-operation and Development) health data showed in 2007 that
usage of antidepressants was increasing across the OECD countries [6].
The efficacy of the SSRIs has been questioned. In a meta-analysis of the newer antidepressants Turner
et al. found publication bias in 74 FDA registered trials; published trials showed a 32% larger effects than
when all trials in the FDA database were included [7].
Another recent meta-analysis showed that the SSRIs were only effective in severe depression (HDRS
score of 25) whereas the effect was quite small for other degrees of depression [8].
2. Objective
Our primary aim was to compare the sales of SSRIs with that of benzodiazepines within the primary
care sector in Denmark. We hypothesized that changes in sales of SSRIs were related to number of
indications and number of products on the market.
3. Methods
We described the total exposure of the Danish population to psychotropic drugs, with a focus on
benzodiazepines and SSRIs, and explored the possible reasons for the changes in sales.
We used data from Hansen and Gyldmark [1] for the period 1970–1981, Danish Drug Statistics for
1981–1991, data from Danish Medicines Information (DLI) for the years 1992 and 1993, and data from
The Danish Medicines Agency (DKMA) for 1994–2007. The data for the whole period were based on the
anatomic therapeutic classification (ATC) system and defined daily doses (DDD) indicated the exposure.
The ATC system is an internationally accepted classification system, which divides all medical products
into 14 anatomical main groups, each with 2 therapeutic subgroups and 2 chemical subgroups [9]. We
have processed data at the levels of the therapeutic main group (N05, N06), the therapeutic subgroup
(N05B, N05C, N06A) and the chemical therapeutic subgroup (N05BA, N05CD, N05CF and N06AB,
N06AX).
DDD is a technical unit expressing the typical maintenance dose for a drug given to an adult for its
main indication. They are “defined” because they are chosen by experts on the background of theoretical
considerations and pharmacological data, rather than from empirically based research of prescriptions
and usage. DDD enable to some degree comparisons of usage over time and between countries [9].
Throughout this article, DDD refers to the number of inhabitants in treatment per 1000 per day (DDD/1000
inhabitants/day). We focused on the primary care sector because the general practitioners in Denmark
prescribe by far most drugs. We related the DDDs and their development over time to the development in
new indications and the number of products. The indications were obtained from the annual Drug Index,
which are based on Summary of Products Characteristics, approved by the Medicines Agency prior to
marketing.
We use the words sales and usage interchangeably, although it is not known how much of sold medicines
are actually used.