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

In 1993, withdrawal reactions on paroxetine were acknowledged and it was recommended that the
drug should not be discontinued abruptly (Medicines Control Agency, 1993). In 1996, withdrawal
reactions were described as “rare and not severe” (Price et al, 1996). In 1998, they were thought to
be a “class effect” (Committee on Safety of Medicines, 1998) and in 2000, isolated reports of more
serious symptoms were recognised (Medicines Control Agency, 2000). In 2004, a proportion of
withdrawal reactions were thought to be “severe and disabling” (Committee on Safety of
Medicines, 2004) and in 2005, they were described as “generally mild to moderate, self-limiting,
but in some patients severe and prolonged” (European Medicines Agency, 2005).
Referring back to early warnings
By the time when the seriousness of benzodiazepine dependence and SSRI withdrawal reactions
were acknowledged by the drug authorities, they referred back to earlier statements, but now
labelled early warnings. For benzodiazepines, it was written in 1988 that, “there has been concern
for many years,” (Medicines Control Agency, 1988) referring to a statement in 1980, which,
however, was that, “the true addiction potential of benzodiazepines was low” (Committee on the
Review of Medicines, 1980). For SSRIs, drug authorities in 2000 stated that, “whilst the withdrawal
symptoms reported were generally not serious, there have been isolated reports of more serious
symptoms” (Medicines Control Agency, 2000) referring back to 1993, although the statements from
that time were, “78 reports of symptoms occurring on withdrawal of paroxetine” and “it has been
used extensively with around 370,000 prescriptions dispensed by the end of 1992” (Medicines
Control Agency, 1993), suggesting that withdrawal reactions was not a problem.
SSRI dependence potential
The dependence potential of the SSRIs was consistently rejected by drug regulators. In 2000, EMA
acknowledged that weak signals of addictive properties had been shown in some studies, but
concluded that available evidence did not “suggest” that SSRIs cause dependence (European
Medicines Agency, 1999/2000). Although the EMA stated that “the lack of evidence for
dependence does not prove the absence of a problem,” the dependence potential was rather firmly
rejected, saying that, “SSRIs do not cause dependence” or “data do not indicate that SSRIs cause
dependence” or “no strong evidence suggest that SSRIs cause dependence.” It was noted that SSRIs
“have been shown to reduce intake of addictive substances like cocaine and ethanol. The
interpretation of this aspect is difficult.”