Effect of valproic acid on dementia onset in patients with bipolar disorder

J Affect Disord. 2016 Sep 1;201:131-6. doi: 10.1016/j.jad.2016.05.010. Epub 2016 May 10.


Background: Valproic acid (VPA) is widely used for treating patients with bipolar disorder; however, it has adverse effects on cognitive function. This study investigated the effect of VPA on the risk of dementia in patients with bipolar disorder.

Methods: We analyzed data from Taiwan's Longitudinal Health Insurance Database 2010. Patients with bipolar disorder who were prescribed VPA for 28 days or at least once per month for 3 consecutive months after the index date were classified as the VPA-treated group, whereas those who did not receive VPA were classified as the VPA-untreated group. Both groups were tracked until the end of 2013 or until loss to follow-up to identify new-onset dementia events. Multivariable Cox proportional hazards models were used to estimate the hazard ratio (HR) of subsequent dementia associated with VPA treatment after adjustment for confounding variables.

Results: The study comprised 5158 patients with bipolar disorder. The multivariable-adjusted HR for newly diagnosed dementia was 1.73 (95% confidence interval [CI], 1.24-2.41, P=0.001) for the VPA-treated group compared with the VPA-untreated group after adjustment for potential confounders. The VPA-treated group had a higher risk than did the VPA-untreated group after propensity score adjustment (HR=1.95, 95% CI=1.42-2.67, P<0.001).

Limitation: Certain variables that may affect the incidence of dementia were unavailable in the claims database and thus could not be considered.

Conclusion: Treating bipolar disorder with VPA increases the risk of dementia by 73-95%.

Keywords: Bipolar disorder; Dementia; Mood stabilizers; Valproic acid.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / physiopathology
  • Cohort Studies
  • Databases, Factual
  • Dementia / chemically induced*
  • Dementia / diagnosis
  • Dementia / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Propensity Score
  • Taiwan / epidemiology
  • Valproic Acid / adverse effects*
  • Valproic Acid / therapeutic use
  • Young Adult


  • Anticonvulsants
  • Valproic Acid