Medscape Article on Bipolar drugs

[Guest guest]

(http://www.medscape.com/sendurl)

(http://www.medscape.com/viewarticle/515431_print)

Quetiapine, Divalproex Equally Effective in Adolescent Bipolar With

Disruptive Behavior

a Moyer, MA

Oct. 25, 2005 (Toronto) — Adolescents with both bipolar disorder and a

disruptive behavior disorder get equal relief from their aggressive symptoms

with

either the atypical antipsychotic quetiapine (Seroquel) or the

anticonvulsant divalproex (Depakote), according to investigators who presented

these

findings here at the joint annual meeting of the American and Canadian

Academies

of Child and Adolescent Psychiatry.

“Few studies have evaluated treatments for this population,†said principal

investigator Drew H. Barzman, MD, in his presentation. He stressed that

adolescents with bipolar disorder often have a disruptive behavior disorder, as

well. Examples of disruptive behavior disorders include conduct disorder,

oppositional defiant disorder, and attention deficit–hyperactivity disorder

(ADHD).

Although divalproex had shown promise for mood lability and temper, no other

investigators had, to Dr. Barzman’s knowledge, tried to see if an atypical

antipsychotic would reduce aggression in such patients. He is an assistant

professor of pediatrics and psychiatry in the Division of Bipolar Disorders

Research at the University of Cincinnati in Ohio.

Dr. Barzman and coinvestigators recruited 50 adolescents, aged 12 to 18

years, who were diagnosed with bipolar I disorder and hospitalized with a manic

or mixed episode. The patients were randomized to receive either quetiapine

or divalproex in a double-blind manner for 28 days. The investigators used

patients’ records in the post-hoc analysis if they scored 14 or more on the

Positive and Negative Symptoms Score (PANSS) Excited Component (EC) and scored

at

least 4 on at least one of these items.

Of the 36 patients who had both bipolar disorder and a disruptive behavior

disorder, 33 (92%) were able to be included based on the PANSS EC criteria.

Those in the quetiapine group received an initial dose of 100 mg on day 1. The

investigators increased the dose to 400 mg on days 4 through 7 and up to 600

mg per day afterward, with the dose given in either one dose or two divided

doses.

Patients in the divalproex group received a dose of 20 mg/kg at bedtime. Dr.

Barzman noted that two psychiatrists who were not blinded and who did not

perform efficacy or tolerability ratings monitored the patients on divalproex

and adjusted the dose as necessary. These adjustments ensured that patients

had a valproic acid serum level in the therapeutic range, 80 to 120 mg/dL.

In the quetiapine group, six patients had comorbid conduct disorder,11 had

oppositional defiant disorder, and five had ADHD. In the divalproex group,

seven had conduct disorder, 11 had oppositional defiant disorder, and six had

ADHD.

At the study’s end, both groups had significant improvements on the PANSS

EC, with an average score change from 18.8 to 10.8 among those on quetiapine

compared with 20.6 to 13.3 in the divalproex group (P < .0001 for each). The

groups had similar improvements on a week-by-week basis, with neither group

showing response earlier than the other.

“No patients discontinued either treatment due to an adverse event,†said

Dr. Barzman. He noted that although adverse events occurred commonly, with 203

such events occurring during the study period, they were typically mild and

transient, consisting of sedation or fatigue, gastrointestinal discomfort,

or headache.

Although placebo-controlled trials will be necessary, psychiatrists should

know that quetiapine may be a useful way to treat children who live with the

confluence of bipolar disorder and disruptive behavior disorders, Dr. Barzman

said. He noted that the use of an anticonvulsant like divalproex is more

common.

The study was funded by AstraZeneca Pharmaceuticals, which manufactures

Seroquel.

AACAP and CACAP Joint Annual Meeting: Abstract C-35. Presented Oct. 20,

2005.

Reviewed by D. Vogin, MD