0
ARTICLE |

Efficacy of Divalproex vs Lithium and Placebo in the Treatment of Mania

Charles L. Bowden, MD; Andrew M. Brugger, MD; Alan C. Swann, MD; Joseph R. Calabrese, MD; Philip G. Janicak, MD; Frederick Petty, MD, PhD; Steven C. Dilsaver, MD; John M. Davis, MD; A. John Rush, MD; Joyce G. Small, MD; Enrique S. Garza-Treviño, MD; S. Craig Risch, MD; Paul J. Goodnick, MD; David D. Morris, PhD; V. Shu, PhD; P. Johnson, MBA; M. Blake, MS; M. Javors, PhD; L. Ereshefsky, PharmD; T. McLeod; A. Shoaib, MBBA; M. Johnson, RN; S. Kimmel, MD; A. Wesley; R. Qualtiere, RN; C. Trivedi; J. Javaid, PhD; J. Peterson; M. Lambert, MD; M. Zielinski, MD; P. Orsulak, PhD; L. Sharp, RN; L. Akers, MS; M. Miller, MD; J. Kellams, MD; G. Woodham, MD; A. Frazer, RN
JAMA. 1994;271(12):918-924. doi:10.1001/jama.1994.03510360044034.
Text Size: A A A
Published online

Objective.  —To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania.

Design.  —Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness.

Patients.  —A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals.

Interventions.  —After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 μmol/L (150 μg/ mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively.

Main Outcome Measures.  —Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia.

Results.  —Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P=.017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P=.004) and 49% for lithium (P=.025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients.

Conclusions.  —Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.(JAMA. 1994;271:918-924)

Topics

Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours

Figures

Tables

References

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

Related Content

Customize your page view by dragging & repositioning the boxes below.

Jobs
brightcove.createExperiences();