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Child Psychiatrist /Adult Psychiatrist

High-Dose Valproate Linked to Significant Weight Gain

TOPLINE: 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.

High-Dose Valproate


  • 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.


  • 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.


"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.


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.


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.


This study was funded by the Swiss National Research Foundation. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.

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