3.3.4.2 Valproic Acid and Divalproex

What type of medication is valproic acid and what are its advantages?

1.    Valproic acid is primarily an anticonvulsant drug. 

2.    Divalproex sodium is a variant of valproic acid. 

3.    Inhibits GABA catabolism and potentiates its postsynaptic effect.

4.    Has one of the best adverse neuropsychological side-effect profiles.

5.    Effective for both seizures and aggressive behaviour 27;28

6.    Effective for a number of psychiatric disorders including bipolar disorder.

What is the evidence supporting the efficacy of valporic acid for aggressive behavior post ABI?

  1. Based on a single RCT, there is Level 1 evidence that valproic acid does not have     any significant neuropsychological side effects, does not prevent post-traumatic seizures, but is effective for controlling established seizures and stabilizing mood.
     
  2. Based on the findings from 2 studies, there is Level 4 evidence that valproic acid and divalproex are effective for reducing a variety of neurobehavioral symptoms including destructive and aggressive behaviours.
     
  3. Overall, Valproate does not appear to have significant neuropsychological side effects, but does appear to stabilize mood and irritability, and control seizures.
  • In one study looked at the efficacy of valproic acid inpreventing seizures post ABI the authors concluded that valproate did not have any significant neuropsychological side effects and was effective for controlling established seizures and stabilizing mood 27.  However, it did not prevent the onset of post-traumatic seizures.
     
  • The effectiveness of valproic acid was investigated for improving destructive and aggressive behaviours, and itwas found to be extremely effective in reducing and improving these negative behaviours 28.
     
  • Kim & Humaran 29 found valproic acidwas effective, as measured by the Clinical Global Impression Scale (a subjective psychiatric rating scale) in reducing various neurobehavioural symptoms including aggression, impulsivity, psychosis, mania, anxiety, hypomania, and irritability.
     
  • Similarly, Chatham Showalter & Kimmel 30 retrospectively found a significant reduction in symptoms of agitation in 29 patients.

Valporic Acid and Dosage

  • The starting dose of valproic acid may range from 125 to 1000 mg.day.  Valproic acid has a very favourable side effect profile, especially for cognitive side effects.  Potential side effects of the medication include gastrointestinal distress, headaches, dizziness, thrombocytopenia, hepatitis and pancreatitis (rare). 

For a greater discussion on the use of valproic acid to treat seizures post ABI see ERABI/Mental Health Issues Post ABI.