Do patients comply with 12-hour lithium blood level timing?Findings from a controlled clinical trial and a real-world clinical setting

BackgroundLithium blood levels are measured routinely 12 hours after lithium dosing, but no study has evaluated the actual compliance of patients with the 12-hour levels. MethodsFirst, we used the US multicenter clinical trial "Bipolar CHOICE" (n=145 patients treated with lithium with N=287 lithium blood tests), where participants reported the time since the last lithium dose at lithium blood tests. Second, we included all lithium blood tests (3,179 individuals, 52,837 blood tests) from hospitals and private practitioners in the Central Denmark Region (CDR, approximate population 1.3 million) during 2012-2022 including time of lithium blood tests and the registered time when patients were supposed to take their lithium dose. ResultsIn Bipolar CHOICE, participants took the lithium blood test at a mean/median of 12.8/12 hours (SD=9.1, IQR=10.5-14) after the lithium dose, but the range was 0.5-120 hours and 44.9% had the blood test taken <10 or >14 hours after the lithium dose. Those with a blood test >14 hours after the lithium dose had significantly lower lithium levels (0.41 vs. 0.64). In the CDR, the mean/median time was 14.5/13.7 (SD=3.8, IQR=12.0-15.8) and 49.7% had the blood test taken <10 or >14 hours after the supposed intake of lithium. Those with >16 hours between lithium intake and the lithium blood test were more often followed by general practitioners and showed higher creatinine concentrations. ConclusionsApproximately half of lithium blood tests do not comply with guideline-based recommendations for 12-hour trough levels, emphasizing the need for solutions solving this clinical need.