Speaker: Carol Robertson-Plouch, DVM, Clinical Research Advisor, Lilly Research Laboratory, Indianapolis, Indiana

(Eli Lilly) effectively reduced the symptoms of mania in adolescents with bipolar disorder. Although this treatment provided therapeutic benefits for these young patients, the risk-benefit ratio in this population should be carefully evaluated, because the severity and magnitude of some adverse events appear to be greater than those seen in adults.

A three-week, randomized, double-blind clinical trial of 161 patients, 13 to 17 years of age, who had a manic or mixed episode of bipolar disorder, was conducted. The patients were randomly assigned, in a ratio of 2:1, to receive either olanzapine (n = 107) or placebo (n = 54).

Olanzapine therapy was begun at 2.5 or 5 mg/day. The dose was increased daily, by 2.5 or 5 mg, to achieve a level of 10 mg/day or more by the fourth visit, up to a maximum tolerable dose of 20 mg or more daily. The mean daily dose was 8.86 mg/day. The primary efficacy analysis was a mean change from baseline to endpoint in Young’s Mania Rating Scale (YMRS) total scores.

Significantly greater reductions in YMRS total scores were noted for olanzapine (-17.7) than for placebo (-10) (P < .001). Treatment was also associated with higher response rates (44.8%, 18.5% for placebo; P=.002), remission (35.2% vs. 11.1% for placebo; P =.001) and response (44.8% vs. 18.5% with placebo, P=.002).

The treated patients also experienced shorter times to reach those criteria. Their time needed to achieve a response was 15 days, compared with 26 days for those receiving placebo, at the 25th quantile; P = .003), and their time needed to achieve remission of mania was 18 days, compared with 26 days for the placebo patients, at the 25th quantile (P = .002)

Somnolence, sedation, increased appetite, and weight gain occurred at significantly greater rates with olanzapine canadian than with placebo.

The olanzapine patients experienced greater mean changes in fasting glucose and total cholesterol levels compared with changes observed in the placebo group. More olanzapine-treated patients gained 7% or more of their baseline body weight compared with patients receiving placebo. Compared with the placebo-treated patients, the olanzapine patients also showed a higher incidence of elevated prolactin levels.

Intramuscular Ziprasidone Controls Acute Agitation

Speaker: Drew H. Barzman, MD, Assistant Professor, Division of Child and Adolescent Psychiatry, University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

A retrospective chart review demonstrated that intramuscular (IM) ziprasidone (Pfizer), a dopamine/sero-tonin antagonist used in the treatment of schizophrenia, was well tolerated and effective for the management of acute agitation in children and adolescents.

These findings were concluded from a retrospective chart review of children and adolescents admitted to psychiatric units at the Cincinnati Children’s Hospital Medical Center between January 1, 2002, and July 11, 2005. During that period, 59 children and adolescents received 77 injections of IM for acute agitation. Medical records were reviewed to determine demographic and clinical information as well as the agent’s tolerability and effectiveness.

The Behavioral Activity Rating Scale (BARS) was used retrospectively to assess clinical response. The primary objective of the study was to evaluate effectiveness and tolerability of IM canadian ziprasidone for impulsivity and reactive aggression in these hospitalized young patients. The secondary response was to examine demographic and clinical factors associated with treatment response.

Overall, the mean ± standard deviation (SD) BARS score decreased from 6.5 ±0.7 to 3.1 ± 1.3. On this scale, 1 represents good behavior, and 7 represents most violent behavior (with restraints required).

Regression analyses showed no significant effects of such demographic factors as age, sex, ethnicity, or primary psychiatric diagnosis on treatment response. Adverse events were rare, with sleepiness or falling asleep recorded in 23 patients. The remainder of adverse events included an increase in seizure frequency, dizziness, nosebleeds, sore muscles, general aches, and confusion. Each event was reported in only one patient.