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

In contrast, according to the precautionary principle even weak signals, from the collection of
adverse effects, rather than definite proofs, could lead to warnings or restrictions in the market
authorisation.
Drug regulators have been guided by the definitions of dependence and withdrawal reactions in
DSM-IV and ICD-10, but not consistently. For example, they preferred the term withdrawal
reactions to the term discontinuation reactions, suggested by the pharmaceutical industry. But when
SSRIs actually met 2 out of the required 3 criteria for the diagnosis of dependence, this was not
accepted by drug regulators as dependence.
Spontaneous reporting of adverse effects
The pharmaceutical companies receive reports about adverse effects from doctors and drug
regulators, assess a possible relationship to their drug, and produce periodic safety update reports,
which they submit to the drug agencies. The underreporting of adverse drug reactions has been
estimated by to be around 90% or more (25), which means that we often lack knowledge about the
frequency and seriousness of adverse effects.
When a drug is marketed, there is only limited knowledge about adverse effects, and the perception
of the balance between benefit and harm will therefore often change over time. For around half of
the drugs, label changes because of serious risks that are only revealed after marketing are
introduced (4). The spontaneous reporting system is therefore slow in detecting signals of harm. For
this reason, the importance of a transparent cause-effect assessment built on a precautionary
principle has been suggested (26, 27). This might be in contradiction to European drug legislation,
which is based on a risk management principle (28). When signals of adverse drug reactions have
turned up it, is the responsibility of drug authorities to re-assess the risk-benefit relation, and to
assess if there is a basis for changes in the market authorization.
Benzodiazepines and abuse potential
In 1967, there were warnings that benzodiazepines were used illicitly, particularly by the youth and
in countercultures (29). In 1979, US Congress initiated a hearing about the “Valium scare”, because
of the “growing of a very serious public health problem of which American people may not be
aware”. As a result of the hearing, the benzodiazepines were regulated by the Drug Enforcement
Agency (DEA) and categorised as Schedule IV drugs in the Controlled Substances Act of 1970,