• adherence
• bioequivalence
• bipolar disorder
• drug monitoring

Background and aim: Enhancing treatment adherence in bipolar disorders is a complex clinical challenge, owing to the complexity of the concept and difficulty measuring adherence, the number of risk factors to consider and the challenge of extracting strategies to promote adherence. The aim of the present preliminary study was to determine if there is a consistent relationship between quantitative measures of salivary and serum mood stabilizers (bioequivalence), and the usefulness of salivary lithium (Li) and valproate (VPA) monitoring as an indicator of its concentration in blood, in order to improve adherence to medication treatment in bipolar patients.
Materials and Methods: Patients affected by DSM-IV-TR bipolar disorder (type I or II) with pre-scheduled, periodic blood analyses for either Li or VPA dosing, were asked to participate and undergo contemporary salivary measurements. Blood levels of both Li and VPA were taken according to standard procedures by the hospital laboratory. Salivary levels of Li were detected with a direct potentiometric method, via an AVL9180 electrolyte analyzer, and measured according to the Nerst equation. Salivary levels of VPA were taken with an immune-assay method based on turbidimetric inhibition, potentiated with competitive homogenous particles. Correlations were calculated with Pearson Product Moment Correlation (Pearson’s r). Statistical analyses were performed with SPSS software (ver 20.0).
Results: A total of 45 patients (33 Li-treated and 12 VPA-treated) affected by bipolar disorder were enrolled in the present cross-sectional study. VPA measures did not permit assessing a blood-saliva bioequivalence due to a high variability in salivary measures. Serum Li levels were all in therapeutic range in the sample (mean: 0.72± S.D., 0.24 mEq/L) and salivary Li levels were 2.5 – 3 times serum levels (mean: 2.02±S.D., 0.76 mEq/L). The correlation between serum lithium and salivary lithium in the sample was statistically significant (r= 0.794).
Conclusions: The advantages of salivary measures are the quick patient administration and the non-invasive nature of the method. An unexpected Li-salivary control could be a way to enhance patients' adherence, giving clinicians a more reliable estimate of patients’ true adherence status, as compared to the routinely scheduled lab tests. Salivary VPA concentrations did not show to be reliable, therefore VPA-treated patients would not benefit from this easy and quick measurement.