Valproic acid-induced parkinsonism in the elderly: a comprehensive review of the literature.

Valproic acid (VPA) is commonly used to treat many psychiatric conditions in the elderly. VPA-induced parkinsonism is a less common but important adverse effect of this drug. The purpose of our study was to conduct a literature review to assess VPA-induced parkinsonism in the elderly. We searched Ovid Medline, PubMed, and Cochrane Database (January 1970 to December 2010) using the key words divalproate, divalproex sodium, valproate, depakote, valproic acid, elderly, aged, Parkinson's disease, and parkinsonism. The Naranjo algorithm was used to assess whether a change in clinical status was the result of an adverse drug reaction. We identified 13 case reports. Available evidence indicated that there was a variable time interval for the development of parkinsonism after VPA therapy. Most cases showed improvement with the withdrawal of the drug, but the rate and extent of improvement was unpredictable. The calculated Naranjo adverse drug reaction scores, for most cases, were between 5 and 6, meaning it was probable that parkinsonism was due to VPA therapy. High clinical awareness is required in diagnosing VPA-induced parkinsonism in the elderly due the presence of comorbid neurodegenerative conditions and the usage of antipsychotics in these patients.