NEW YORK – Sparse evidence from double-blind, placebo-controlled trials backs the effectiveness of treatments for acute mania in children and adolescents with bipolar I disorder, but results from ongoing trials should be available soon, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
Double-blind, placebo-controlled trials have been conducted with olanzapine (Zyprexa), topiramate (Topamax), and oxcarbazepine (Trileptal) for the treatment of acute mania in children and adolescents, but other drug trials are yet to be completed, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook.
Trials of that nature are underway for divalproex (Depakote) and the atypical antipsychotics risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify).
No trials have been planned for lithium or clozapine (Clozaril).
Based on the primary end point of the amount of change in the Young Mania Rating Scale (YMRS) from baseline, only olanzapine has shown statistically significant efficacy, in comparison with placebo. Topiramate and oxcarbazepine have not reached statistical significance on this end point in a double-blind, placebo-controlled trial, she said.
In the olanzapine trial of patients aged 13–17 years, 49% of the 107 adolescents who received active treatment had greater than 50% improvement in their YMRS score, compared with 22% of the 54 patients who received placebo.
The rate of remission at the end of 3 weeks of treatment also was significantly higher for olanzapine (35%) than for placebo patients (11%).
The oxcarbazepine trial of 116 children and adolescents appeared to show some efficacy of the anticonvulsant in patients aged 7–12 years, because YMRS scores improved by greater than 50% in significantly more patients in that age group who received oxcarbazepine (41%) than in those who received placebo (17%).
Adolescents aged 13–18 years did not differ significantly in their response to carbamazepine (43%) or placebo (40%).
In the topiramate trial, mean YMRS scores improved from 31.7 to 22 for the 29 patients who received the anticonvulsant and from 29.9 to 25.2 for the 27 patients who received placebo.
The topiramate study was stopped early because the separate adult trials that involved topiramate failed to show efficacy for acute mania (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:539–47).
In the topiramate and olanzapine trials, the clinician-rated scale of Clinical Global Impressions showed a statistically significant difference in the percentage of patients who were improved or very much improved.
In a head-to-head, double-blind, randomized trial of 50 patients, divalproex and quetiapine appeared to have similar efficacy in treating acute mania in hospitalized adolescents.
YMRS scores at baseline improved from an average of about 35 in each group to 17 in divalproex patients and to 13 in quetiapine patients.
“There wasn't a [significant] difference, because both of them work,” Dr. Carlson said.
No double-blind, placebo-controlled trials of lithium in children and adolescents for acute mania have been conducted, even though the drug has been used openly in adults and kids since the 1950s.
Most of the open-label, discontinuation, and/or add-on trials of lithium, divalproex, and carbamazepine have shown positive results for the treatment of acute mania in children and adolescents.
Similar results have been reported with risperidone, olanzapine, and quetiapine.
Polypharmacy studies in which a drug is added to augment the effects of another medication appear to be beneficial in patients who are able to tolerate the combination, Dr. Carlson said.
In one randomized, double-blind study of 30 patients, a combination of divalproex and quetiapine resulted in a significantly higher response rate (87%) than did divalproex plus placebo (53%), she noted.
Patients who took the combination also had significantly greater improvement on mean YMRS scores from baseline to 42 days (from 34 to 10 vs. from 31 to 17) (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:1216–23).
The combination of divalproex and lithium also appears effective when tolerated.
An open-label study of this combination showed that 42 of 90 children and adolescents with mostly bipolar I disorder met stringent criteria for remission after an average of 13 weeks of treatment.
The 90 patients had an average YMRS score of 22 at baseline; this score improved to a mean of less than 1 in the patients who remitted (J. Am. Acad. Child Adolesc. Psychiatry 2003;42:895–901).