Prevalence of Therapeutic Drug Monitoring for Lithium and the Impact of Regulatory Warnings: Analysis Using Japanese Claims Database

Abstract

Background:Therapeutic drug monitoring (TDM) for lithium is recommended in guidelines; however, the prevalence of TDM for lithium is seldom reported. We have therefore investigated the prevalence of TDM for lithium and evaluated the impact of the regulatory warnings requiring routine TDM for lithium.Methods:Monthly claims data covering around 1.7 million persons aged 20–74 years old during the period January 1, 2005, and March 31, 2015, were evaluated. All patients who had at least one prescription for lithium were selected and included to calculate the annual prevalence of TDM for lithium. Also we assessed whether the 2 regulatory warnings requiring routine TDM for lithium and issued in April 2012 and September 2012 had an impact on TDM for lithium, using segmented regression analysis.Results:Between 2005 and 2014, 136,956 prescriptions of lithium were issued to 5823 patients, and the annual prevalence of TDM for lithium was 14.9% (95% confidence interval, 14.7%–15.1%). The analysis revealed that the mean prevalence increased abruptly by 6.9% (P = 0.001) after the regulatory warning in April 2012, whereas that the warning in September 2012 decreased by 1.2% (P = 0.47). There was no significant change in trends of period prevalence after the warning in April 2012 (April 2012–August 2012) compared with prevalence before the warning (April 2010–March 2012). Similarly, no significant change was observed in the trends before (April 2012–August 2012) and after (September 2012–March 2014) the subsequent warning in September 2012.Conclusions:Results showed that the prevalence of TDM for lithium was low, although TDM for lithium was strongly recommended by the guidelines. Regulatory warnings requiring compliance with the measurement of blood levels during treatment with lithium, issued twice during the five-month period, were associated with an increase in the prevalence of TDM for lithium. However, the impact of the second warning was not remarkable compared with the first warning.

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

“…In contrast, just 45% (17/38) of the studies in the “others” group were presented as ineffective or partially effective. But 53% (20/38) described an effective impact, and only 2% examined an unintended effect.…”

“…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 …”

“…-20,23,25,26,29,31,39-44,48,50-52,54,58,64,67,68,71,73,76,81 In 12 studies, the authors concluded that the content of the safety warnings investi-,22,24,25,33,34,56,61,65,78,79,82 In 26 studies, a partial change in drug therapy was shown 27,30,32,33,[35][36][37][38][45][46][47]49,53,55,57,59,62,63,66,69,70,74,77,[83][84][85]. …”