Valproic acid utilization among girls and women in Stockholm: Impact of regulatory restrictions

Abstract

SummaryObjectiveIn November 2014, the European Medicines Agency (EMA) strengthened restrictions on the use of valproic acid in girls and women of childbearing potential. The objective of this study was to determine whether there has been a change in initiations of valproic acid treatment to females after the regulatory restrictions and to assess if such changes differed between indications (epilepsy and psychiatric disorder).MethodsAn interrupted time‐series analysis was conducted using all initiations of valproic acid in Stockholm, Sweden. from January 2011 to June 2017. Female and male patients aged 0–45 years with a recorded diagnosis of epilepsy and/or a psychiatric disorder were compared.ResultsBefore the EMA warning, a decline in trend of valproic acid initiations was seen in patients with epilepsy. After the warning, a significant decrease of valproic acid initiations was seen in women with a psychiatric disorder, but not in women with epilepsy.SignificanceThe regulatory warning appeared to have significantly influenced valproic acid initiations in women of childbearing age with a psychiatric disorder. No effect was seen in women with epilepsy, probably because the decline had started long before.

Do drug‐related safety warnings have the expected impact on drug therapy? A systematic review

“…All of the 70 publications included are observational studies based on routinely collected health data, which included health insurance or hospital records. Thus, no RCTs were found for the defined search period.…”

“…Two publications examined safety warnings for two mutually independent substances each, that is, 70 publications reported 72 studies. If a study contained multiple characteristics, the characteristics of these studies were counted multiple times in the following analyses, for example, studies examining more than one safety warning on one substance or substance group (multiple counts for safety warnings per study) or where a safety warning included multiple recommendations, for example, indication limitations and new adverse reactions (multiple counts for the content of the safety warning) were also subject to multiple counting.…”

“…In 12 studies, the authors concluded that the content of the safety warnings investigated did not lead to a change in drug therapy . In 26 studies, a partial change in drug therapy was shown …”

“…Table summarises the results of 34 studies regarding “psychotropic drugs.” A total of 62% (21/34) of the studies in the “psychotropic drugs” group were described as ineffective or partially effective, that is, the investigated safety warning showed no or only a partial impact on drug therapy. Only 23% (8/34) of the studies described an effective impact on drug therapy as a result of the safety warning.…”

“…The criterion of data cleaning of the underlying routinely collected health data was not described in any of the studies. Apart from the lack of data cleaning, some of the studies described the remaining items of the STROBE and RECORD checklists extensively and transparently …”