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Amphetamine Mixed Salts May Be Effective for ADHD in Bipolar Disorder

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 1/12/2005
  • Valid for credit through: 1/12/2006, 11:59 PM EST
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Target Audience and Goal Statement

This article is intended for primary care physicians, psychiatrists, and other specialists who care for young patients with bipolar disorder and ADHD.

The goal of this activity is to provide the latest medical news to physicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Describe the effect of eight weeks of divalproex sodium monotherapy on mania symptoms in pediatric patients with comorbid bipolar disorder and ADHD.
  • Describe the effect of two weeks of amphetamine salts on ADHD symptoms when added to divalproex sodium in pediatric patients with comorbid bipolar disorder and ADHD.


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  • Laurie Barclay, MD

    Laurie Barclay is a freelance reviewer and writer for Medscape.


    Disclosure: Dr. Barclay has reported no significant financial interests.


  • Gary Vogin, MD

    Senior Medical Editor, Medscape


    Disclosure: Dr. Vogin has reported no significant financial interests.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor of Family Medicine; Director, Division of Faculty Development, University of California, Irvine School of Medicine, Irvine, California


    Disclosure: Dr. Lie has reported no significant financial interests.

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Amphetamine Mixed Salts May Be Effective for ADHD in Bipolar Disorder

Authors: News Author: Laurie Barclay, MD CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 1/12/2005

Valid for credit through: 1/12/2006, 11:59 PM EST


Jan. 12, 2005 — For attention deficit hyperactivity disorder (ADHD) in patients with bipolar disorder, amphetamine mixed salts are effective after mood stabilization with divalproex sodium, according to the results of a study published in the January issue of the American Journal of Psychiatry.

"Stimulants are the agents of choice for ADHD that is uncomplicated by bipolar disorder," write Russell E. Scheffer, MD, from the University of Texas Southwestern Medical Center at Dallas, and colleagues. "To our knowledge, there are no prospective randomized, controlled trials of stimulant treatment of ADHD concurrent with pediatric bipolar disorder."

In an eight-week trial, 40 subjects aged six to 17 years entered open treatment with divalproex sodium. Diagnosis was bipolar I disorder in 77.5% of patients, and bipolar II disorder in 22.5%, based on clinical interview and confirmed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia. Young Mania Rating Scale score was 14 or higher in all subjects.

During open-label treatment with divalproex sodium, 32 subjects achieved at least a 50% reduction in Young Mania Rating Scale scores, but only three subjects had significant improvement in ADHD symptoms on the Clinical Global Impression (CGI) of Improvement.

Thirty subjects subsequently entered a four-week randomized, double-blind, placebo-controlled, crossover trial of mixed amphetamine salts, 5 mg, by mouth twice daily, and patients continued to receive divalproex sodium. Mixed amphetamine salts were significantly more effective than placebo for ADHD symptoms, and there were no significant adverse effects or worsening of manic symptoms.

"Pediatric patients with bipolar disorder and concurrent ADHD can be safely and effectively treated with mixed amphetamine salts after their manic symptoms are stabilized with divalproex sodium," the authors write. "Divalproex sodium alone (8-week trial) is not an effective treatment for ADHD in the context of bipolar disorder."

Study limitations include less than maximally effective dose of mixed amphetamine salts, divalproex sodium doses not "pushed," limited generalizability of the findings, and failure to sufficiently address the long-term outcomes and safety of the combination of divalproex sodium and mixed amphetamine salts beyond 12 weeks.

"Additional information is needed on the optional dosing of both divalproex sodium and mixed amphetamine salts for these patients," the authors conclude. "A larger, more generalizable trial is indicated."

The Stanley Medical Research Institute helped support this study.

Am J Psych. 2005;162:58-64

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