Valproate

High-Dose Valproate Linked to Significant Weight Gain

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High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.

METHODOLOGY:

  • The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
  • The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
  • The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.

TAKEAWAY:

  • Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
  • Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
  • The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
  • In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
  • The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.

IN PRACTICE:

“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.

SOURCE:

Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, and the Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online on March 27, 2024, in the Journal of Clinical Psychiatry.

LIMITATIONS:

The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.

Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure

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Abstract

BACKGROUND

Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.

METHODS

We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.

RESULTS

The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score–adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.

CONCLUSIONS

The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate.

Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure

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Abstract

BACKGROUND

Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.

METHODS

We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.

RESULTS

The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score–adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.

CONCLUSIONS

The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate

PRAC issues warning for Valproate use during pregnancy

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https://speciality.medicaldialogues.in/prac-issues-warning-for-valproate-use-during-pregnancy/