Lower effectiveness of divalproex versus valproic acid in a prospective, quasi-experimental clinical trial involving 9,260 psychiatric admissions.
OBJECTIVE
The authors examined clinical differences between divalproex sodium and generic immediate-release valproic acid.


METHODS
This 6-year prospective, quasi-experimental clinical trial compared the effectiveness and tolerability of divalproex and valproic acid. The dependent variables were length of hospital stay, rehospitalization rate, and adverse drug reactions in 9,260 psychiatric admissions.


RESULTS
Inpatients who initially received divalproex sodium had a 32.7% longer hospital stay and 3.8% higher readmission rate than did patients who initially received valproic acid. Initial treatment with divalproex prolonged length of stay by 30.3% in patients treated with divalproex and valproic acid during different admissions. After other variables were controlled by multiway analysis of variance, the hospital stay of patients who continued the initial medication was 15.2% longer (2.0 days) for divalproex than valproic acid. Switching medications was more common for valproic acid, partly because of study design. Medication intolerance occurred in approximately 6.4% more patients taking valproic acid than divalproex. However, switching from valproic acid to divalproex did not significantly prolong length of stay, over that for continuous divalproex, or increase the rehospitalization rate.


CONCLUSIONS
Lower peak valproate concentrations with divalproex sodium may have enhanced tolerability but may also explain the lower effectiveness. Extended-release divalproex could lower effectiveness further and require higher doses. Thus, inpatients are better served by beginning with generic valproic acid and by changing to delayed-release divalproex only if intolerance occurs. This would save up to one-third of inpatient costs and two-thirds of a billion dollars yearly in medication costs.
Wassef
Adel A
AA
Harris County Psychiatric Center, University of Texas Health Sciences Center, Houston, TX 77021, USA. awassef@mind.hcpc.uth.tmc.edu
Winkler
Diane E
DE
Roache
Ann L
AL
Abobo
Vivian Boma
VB
Lopez
Lina M
LM
Averill
John P
JP
Mian
Ayesha I
AI
Overall
John E
JE
D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D016568:Drugs, Generic / Q000627:therapeutic use; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000523:psychology; D010359:Patient Readmission / Q000706:statistics & numerical data; D011446:Prospective Studies; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D016568:Drugs, Generic; D014635:Valproic Acid