Weight loss surgery has become more common in the United States because of the increasing rates of obesity. The physiological changes caused by weight loss surgery have the potential for clinically significant changes in the pharmacokinetic parameters of mood stabilizers, including valproic acid (VPA). A patient with a history of Roux-en-Y gastric bypass and bipolar disorder was hospitalized because of mania. The dosing regimen of the VPA was changed multiple times due to unexpectedly low and inconsistent trough levels. Despite a significant increase in the total daily dose, the final trough level obtained was not significantly different than the initial level. The VPA was changed from the delayed-release to the immediate-release formulation to achieve better absorption. However, no trough level was obtained after this change. Weight loss surgeries, such as Roux-en-Y gastric bypass, may continue to impact the pharmacokinetic parameters of VPA for several years after the procedure. This patient was titrated to a dose of 39 mg/kg/day (typical range 20-30 mg/kg/day) with minimal change in level. Pharmacokinetic changes are a concern in the use of mood stabilizers, including VPA, after weight loss surgery. Close monitoring is essential for safe and effective treatment. If strict drug level monitoring is not an option, it may be preferable to consider an alternative mood-stabilizing treatment. Switching to the immediate-release formulation of VPA may also be an option; however, further investigation is required to determine if this makes a clinical difference in the management of bipolar disorder.
