Clinical correlates of valproate augmentation in refractory bipolar disorder

We examined the clinical correlates of valproate (VPA) therapy in refractory bipolar disorder. Retrospective chart review was used to collect demographic and clinical data including present diagnosis, diagnosis at illness onset, duration of illness, number of hospitalizations, VPA dose, side effects, and maximum serum concentration. Global response was rated once patients serum VPA exceeded 50 mg/dL. The charts of all inpatients admitted over a two-year period and treated with VPA for acute episodes of bipolar disorder in manic, mixed, or depressed phase were reviewed. Seventeen of these patients began VPA augmentation while hospitalized and became the cohort for review. Patients were excluded if VPA was started prior to admission or the patient was discharged less than one week after drug initiation. Patients were not excluded on the basis of EEG, CT, or neurological exam findings. Overall, 12 of 17 (71%) of the patients showed a moderate or marked improvement while 5 of 17 (29%) showed mild or no response. Responders were older and had a longer duration of illness with an increased number of hospitalizations. There was a strong trend for responders to achieve a higher serum VPA level. A significant positive correlation was found between response in acute mania and psychotic symptoms at first episode of illness.