Inflammatory cytokines as predictors of therapeutic response to valproate in patients with comorbid alcohol use disorder and bipolar disorder.

Objective: Alcohol use disorder (AUD) is a chronic condition commonly associated with bipolar disorder (BD). We previously reported that valproate (VPA) can decrease drinking in some patients with comorbid AUD/BD. Predictors of treatment response to VPA, however, are yet to be elucidated, and it is not possible to prospectively identify patients who may benefit from the course of VPA. Both pathogenesis of AUD/BD and mechanism of action of VPA are related to inflammation (AUD/BD confers a pro-inflammatory state, while VPA has anti-inflammatory properties) which is associated with an altered count of plasma extracellular particles. Approach: Patients with co-occurring AUD/BD were recruited and treated with VPA for 3 months at an average dose of 1,000 mg a day. Clinical response was defined as a decrease in proportion of weekly heavy drinking days (defined as ≥5 drinks per day for men and ≥4 drinks per day for women). Levels of inflammatory cytokines in plasma were measured using MAGPIX Luminex. Counts of extracellular plasma particles were determined using flow cytometry with size beads. Results: We found that plasma levels of C-reactive protein (CRP) at baseline were significantly increased in patients who responded to VPA. We did not find the difference in counts of extracellular particles between responders and non-responders. In line, we observed that treatment with VPA conferred an anti-inflammatory effect but did not alter counts of plasma particles. Conclusion: This pilot study indicates that patients with AUD/BD who have increased levels of CRP are more likely to benefit from the treatment with VPA.