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

21876/Seroxat%2C+filmovertrukne+tabletter+20+mg+og+30+mg.doc
2005 European medicines Agency
Doc. Ref. EMEA/CHMP/PHVWP
/397128/2005
dependence.]
Generally these
events[withdrawal symptoms]
are mild to moderate and are
self-limiting, however in some
patients they may be severe
and/or prolonged.
Core SPC
Wording for
SSRIs
The first warnings about dependence with benzodiazepines came approximately 20 years after the
first report showing withdrawal symptoms. This warning was based on the belief by the authorities
that very few people were dependent. In contrast to this, it only took 5 years before it was
communicated that withdrawal reactions were connected to SSRIs. In the meantime, however, the
definition of dependence had been changed with the consequence that symptoms that formed the
benzodiazepine dependence also formed the SSRI withdrawal reactions. For a longer period it was
the perception of the authorities, that SSRIs withdrawal reactions only affected few patients and that
the symptoms were relatively mild.
There is interesting literature pertaining to the regulation of the newer antidepressants (60). It is
described that the regulatory inertia was illustrated through the 2004 CSM Expert Working Group
on the safety of SSRIs (61). The report pointed to lack of evidence of risk, because a number of
essential studies had never been performed. Still, 10-15 years after licensing the SSRIs, the MHRA
had received no convincing evidence of the incidence of SSRI withdrawal reactions.
Patients reported symptoms as dependence to the SSRIs, but as the dependence definition was
changed in 1987, as shown in study 2 in this thesis, the reported symptoms were not recognised as
dependence but as withdrawal syndrome. However, in the WHO Uppsala Monitoring Centre
database three SSRIs were among the 30 highest-ranking drugs in the list of drugs for which
dependence has ever been reported by June 2002 (62).
We related the findings in the documents to the risk management principle, described in legislation,
and the precautionary principle, described in literature.
In the light of the precautionary principle and the risk management principle, the results of our
study can be understood in two ways. Seen from a precautionary principle, the drug agencies have
41