Guidelines for treatment-resistant mania in children with bipolar disorder.

OBJECTIVE: To implement a treatment algorithm to operationalize treatment-resistance and improve patient outcomes in youth with pediatric bipolar disorder (PBD). The term "treatment resistance" was operationally defined as significant persistent symptoms following the application of a treatment algorithm. METHOD: Youth (6-17 years of age, n=120) with treatment-refractory bipolar I or II disorder, currently in a manic or mixed episode, were treated in accordance with the following 3 step algorithm: (1) removal of destabilizing agents (antidepressants, gamma aminobutyric acid [GABA]-agonists, and stimulants), (2) optimization of antimanic agents, and (3) use of a limited number (E 2) of mood stabilizers. The primary efficacy measure was change in scores on the Young Mania Rating Scale (YMRS) over the 6-month treatment course. Response was defined as repeated YMRS scores E 12. RESULTS: The sample was dichotomized into responders and non-responders. Both responders and non-responders improved significantly, with responders improving by a greater margin (d=3.2). At the end of 6 months, 75.8% of subjects demonstrated a significant and stable decrease in manic symptoms consistent with symptomatic remission (YMRS E 12). None of the subjects withdrew from the clinical process due to adverse events. CONCLUSION: The application of this proposed treatment algorithm allows for more accurate identification of true treatment resistance and can significantly reduce manic symptoms in patients previously described as having treatment-refractory bipolar disorder.

Rapid quetiapine loading in youths with bipolar disorder.

OBJECTIVE: The aim of this study was to evaluate the tolerability and efficacy of rapid quetiapine loading in youth diagnosed with pediatric bipolar disorder (PBD). METHOD: Quetiapine was started at 100 mg/day, and increased to 400 mg/day by day 5 in 75 bipolar children (6-16 years), presenting in an acute manic or hypomanic episode. Subsequent dose adjustments were predicated on the clinical picture. Response was defined as a ≥ 50% reduction in baseline scores on the Young Mania Rating Scale (YMRS). Clinical Global Impression-Improvement Scale (CGI-I) scores of "2 much improved" or "1 very much improved" were used as secondary measures of response. Remission was defined as a YMRS score of ≤ 12. Adverse events, blood pressure, weight change, somnolence, extrapyramidal syndrome (EPS), and akathisia were monitored to determine tolerability. RESULTS: At 8 weeks, 94% of the sample had a CGI-I score ≤ 2, and 70% were in remission at 6 months. Sedation was reported by 50% of subjects during the first week; this rate dropped to 5.6% at 6 months. CONCLUSION: The findings indicate that rapid dose administration of quetiapine in children and adolescents with PBD is generally well tolerated and efficacious.