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Overnight Versus Progressive Conversion of Multiple Daily-Dose Divalproex to Once-Daily Divalproex Extended Release: Which Strategy Is Better Tolerated by Adults With Intellectual Disabilities?

Hellings, Jessica A. MD*; Barth, Francis X. DO*; Logan, Marilyn RN*; Cook-Wiens, Galen MS; Osorio, Ivan MD; Reed, Ronald C. PharmD§

Journal of Clinical Psychopharmacology: October 2009 - Volume 29 - Issue 5 - p 492-495
doi: 10.1097/JCP.0b013e3181b639b4
Brief Reports

Divalproex (DVP) delayed release and DVP extended release (DVP ER) are approved by the Food and Drug Administration for bipolar disorder, epilepsy, and migraine prophylaxis. Divalproex ER is given once daily, improving compliance and reducing adverse events. Overnight switch to DVP ER is advised in the package insert but could produce more adverse events in this susceptible population. In this pilot study, we compared tolerability of overnight versus gradual switching to DVP ER in 16 adults with intellectual and developmental disabilities receiving DVP, in 9 for epilepsy and in all 16 for comorbid bipolar disorder. The study design was open with parallel groups. Sixteen subjects with intellectual and developmental disabilities were randomized to overnight or gradual conversion for 4 to 6 days. A blinded rater completed the Multidimensional Observation Scale for Elderly Subjects on days +1, +4, and +8 after the switch began. We found no major differences between the 2 groups at each time point. Neither group of subjects, except for 1 subject in the overnight group, manifested sedation, seizures, worsening of tremor, or gastrointestinal adverse events. One subject in the overnight group manifested acute diarrhea and vomiting, followed by a very brief tonic leg seizure 6 days later. Larger studies are warranted.

From the Departments of *Psychiatry and Behavioral Sciences, †Biostatistics, and ‡Neurology, University of Kansas Medical Center, Kansas City, KS; and §Abbott Laboratories Inc, Abbott Park, Chicago, IL.

Received December 4, 2008; accepted after revision July 6, 2009.

Reprints: Jessica A. Hellings, MD, Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, MS 4015, 3901 Rainbow Blvd, Kansas City, KS 66160 (e-mail:

This study was funded by Abbott Laboratories Inc.

© 2009 Lippincott Williams & Wilkins, Inc.