A recent longitudinal study conducted in a psychiatric population has shed light on the association between valproate (VPA) dosage and treatment duration with weight gain. Weight gain is a well-known side effect of VPA usage, but it is unclear whether these adverse effects are dose dependent. Moreover, these side effects are understudied in psychiatric populations.

The study, which included 215 patients (Figure) with various psychiatric conditions (see Figure), aimed to assess the relationship between VPA dosage, duration, and weight gain over a one-year period. Patients were prescribed VPA doses ranging from 250 mg/d to 3,000 mg/d, with the median dose set at 1,300 mg/d. Those receiving higher doses, especially above the median, were more likely to be male, diagnosed with bipolar disorder or schizoaffective disorder, hospitalized, and with higher baseline weight and BMI. Treatment duration was divided into pre- and post-3 months, aligning with previous findings indicating significant weight gain within the initial 2-3 months of VPA administration.

A significant association was found in patients receiving doses equal to or above the median dose of 1,300 mg/d, but not for those receiving lower doses. A 500 mg increase in VPA dosage was associated with a +0.52% increase in body weight per month over the course of a year, and the association between dose and weight change was significant regardless of treatment duration. However, for every month of treatment, a +0.16% increase in weight was found. An association between VPA dosage and weight gain was found in men, with each 500 mg increase in dosing resulting in a +0.59% increase in body weight per month (P < .001). While women also showed a trend towards weight gain (+0.40% per month), it did not reach statistical significance (P = 0.09) (Figure). Given previous studies have found opposing trends regarding VPA dosing and women, this finding suggests a potential confounding variable wherein women might be prescribed lower doses or are more carefully monitored for weight gain. No associations were found for VPA dose and blood glucose, lipid levels, or blood pressure.

In conclusion, this study provides evidence that VPA doses at or above 1,300 mg/d are associated with weight gain in psychiatric patients, underscoring the importance of prescribing the lowest effective doses to mitigate weight gain. Furthermore, it is important to closely monitor weight gain during the initial months of treatment, particularly for doses exceeding 1,300 mg/d where clinically significant weight gain (>5% in one month) may pose long-term health risks.

Reference:
Grosu C et al. J Clin Psychiatry 2024; 85(2):23m15008. Abstract.