Reversible Valproic Acid-Induced Parkinsonism and Cognitive Impairment in an Elderly Patient With Bipolar Disorder I

Valproic acid (VPA) is approved by the Food and Drug Administration (FDA) for the treatment of manic or mixed episodes associated with bipolar disorder. VPA is also used off-label to treat other conditions in psychiatry such as impulse control disorders, major depression, and posttraumatic stress disorder (PTSD). Although VPA is mostly well-tolerated, common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea), neurological symptoms (sedation, ataxia, tremor), weight gain, and alopecia. Less common adverse effects include VPA-induced parkinsonism and cognitive impairment. We describe a patient who developed parkinsonism and cognitive impairment eight years after starting divalproex sodium for bipolar disorder, type I. Over time, the patient's parkinsonian symptoms progressed, and the motor symptoms were partially responsive to carbidopa/levodopa. Her mild cognitive impairment was, for the most part, stable on donepezil. Rapid discontinuation of divalproex sodium resolved the parkinsonian symptoms as well as the cognitive impairment. A brief review of the literature regarding VPA-induced parkinsonism and cognitive impairment in adults is included. Given the reversible nature and potential severity of VPA-induced parkinsonism, improved recognition in psychiatric populations is critical, particularly after extended VPA exposure. To the best of our knowledge there are no reports describing the onset of VPA-induced parkinsonism in psychiatric patients more than eight years after starting VPA.