This is the first study to systematically analyse ADRs for nervous system medications reported by consumers to the EV database. Almost all ADRs, except for those reported for parasympathomimetics, were serious and several fatal cases were reported. Reported ADRs were predominantly of the type nervous and psychiatric disorders and general disorders. The majority of ADRs were reported for pregabalin, varenicline and venlafaxine.
ADRs by type and seriousness
The most frequently reported ADRs for nervous system medications were of the type nervous and psychiatric disorders and this finding was expected due to the mechanism of action of the reported nervous system medications. Additionally, a large number of ADRs of the type general disorders and administration site conditions and gastrointestinal disorders were reported, and this finding was also in line with results in previous consumer studies [5–13]. More than one half of reported ADRs were serious, however this reporting pattern was not surprising, since countries were not requested to report non-serious ADRs to the EV database during the study period [16].
ADRs by therapeutic groups
The largest number of ADRs was reported for antiepileptics and antidepressants, which can be explained by the frequent use of these medications in adults [20]. A high number of ADRs were reported for varenicline but only few were serious. In 2007, based on consumer reports in the USA, there was a high media attention on the increased risk of serious ADRs such as suicidal ideation and occasional suicidal behaviour, erratic behaviour and drowsiness reported for varenicline leading to black box warnings in the USA (July 2009) [21]. The ADR signal was later confirmed in a meta-analysis [22]. The high number of ADRs reported for varenicline by European consumers could have been stimulated by this media attention; however, the majority of reported ADRs were non-serious. For pregabalin a large number of the ADRs “drug ineffective/drug effect decreased” were reported, probably because this side effect can easily be assessed, and is very obvious compared to many other types of ADRs. To evaluate whether ADRs reported for pregabalin and varenicline can act as early warning for new ADR signals more in-depth analysis of the ADR reports should be conducted.
Strengths and limitations of this study
The strength of this study is that data comprised all ADRs reported by consumers in Europe, which were forwarded to the EV database during a five-year period and present in the database by March 2012. A major limitation to this study is that we do not know to which extent the causality of these ADRs can be confirmed, and this has implications for the interpretation of the findings [2]. The value of consumer reports in detection of new ADR signals remains unclarified due to the lack of information about causality. In this study, we did not evaluate the validity of the consumer reports since we only had access to the data entered into the EV database and not the original reports. Spontaneous reporting systems suffer from various barriers, such as incomplete recognition of ADRs, administrative barriers to reporting and low data quality, all of which may result in under-reporting of important serious and rare events [2]. ADRs that are non-serious or already known may be over-reported; however, this study provides information on reported ADRs, and this information contributes to broadening the knowledge on medicine safety. Before July 2012 countries were only obliged to report serious consumer reports to EV, which may explain the large number of serious ADRs found, and the low number of non-serious consumer reports. Therefore there may be additional non-serious consumer ADR reports present in the regulatory agencies. With the new pharmacovigilance regulation that came into force in July 2012 the share of serious consumer reports in EV will probably decline although the total number of consumer reports is expected to increase.
Hence, it is not possible to generalize from data reported to the EV database to the other EU member states. Spontaneous reports are an important source of information about new and previously unrecognized ADRs, and the value of spontaneous reporting schemes lies in their ability to act as hypothesis-generating procedures [2]. Therefore, EMA should continue to systematically survey and analyse ADRs reported by consumers in order to signal previously unknown ADRs. Another important issue to be investigated in future studies is to which extent individuals suffering from ADRs later recover from the reported reactions.