The Effect of Individual Valproic Acid and Albumin Variation on the Risk of Episodes in Patients with Bipolar Disorder

Aim: This study aimed to investigate the association between the coefficient of variation (CV%) of valproic acid (VPA) and albumin levels and mood episode status in patients with bipolar disorder who maintained therapeutic VPA concentrations. Material and Method: Patients diagnosed with bipolar disorder who had been under follow-up for at least two years between 2018 and 2023 were retrospectively analyzed. Inclusion criteria required at least three annual measurements of simultaneous serum VPA and albumin levels, with VPA consistently within the therapeutic range (45–100 µg/mL). Patients were categorized based on episode occurrence. Mean values, standard deviation (SD), and CV% were calculated for VPA and albumin levels. Results: A total of 90 patients with bipolar disorder were included, with 45 experiencing episodes and 45 remaining episode-free. The mean of the last six albumin measurements was significantly lower in the episode group (t=–2.688, p=0.009). While the CV% of total VPA levels did not differ significantly between groups, the CV% of albumin-adjusted VPA levels was significantly higher in the episode group (z=–2.005, p=0.045). Episode frequency showed a statistically significant but weak positive correlation with both normalized SD (r=0.281, p=0.007) and normalized CV% (r=0.260, p=0.013). Conclusion: This study found that individuals with bipolar disorder who experienced episodes had significantly lower serum albumin levels, and that albumin-adjusted VPA fluctuations showed a weak but positive correlation with episode occurrence. Prioritizing the CV% of albumin-adjusted VPA measurements may play a significant role in monitoring episode risk in patients with bipolar disorder.